Michelle Odden

All Publications

• The Influence of Frailty: How the Associations Between Modifiable Risk Factors and Dementia Vary. Annals of epidemiology Gao, L., Tang, J., Odden, M. C., Wu, C. 2024

  Abstract

  BACKGROUND: The Lancet Commission has highlighted 12 modifiable risk factors for dementia. However, the effects of addressing these risk factors among the heterogeneous older adult population is not fully understood. We compared the association between risk factors and dementia by frailty, conceptualized as an explanation for the underlying health heterogeneity in old age.METHODS: Data were from the UK Biobank, a cohort study with over 500,000 participants aged 37-73 between 2006 and 2010. Frailty was measured by five criteria: slowness, weakness, exhaustion, inactivity, and shrinking. Participants meeting 0, 1-2, and 3-5 criteria were considered non-frail, prefrail, and frail, respectively. We included 13 modifiable risk factors. We used logistic regression to determine the associations of risk factors with 10-year dementia among non-frail, pre-frail, and frail individuals, respectively. Additionally, we adopted a g-computation method to estimate the individual and combined population intervention effects (PIE) of the risk factors for dementia.RESULTS: Of 381,419 participants, 58.4%, 38.2%, and 3.4% were classified as non-frail, pre-frail, and frail, respectively. Except for smoking, depression, and excessive alcohol use, the other 10 risk factors had a stronger association with dementia among frailer individuals. We observed the highest PIEs among frail individuals when considering hypothetical interventions targeting low education, physical inactivity, central obesity, social isolation, hearing impairment, hypertension, diabetes, high nitrogen dioxide (NO2) exposure, high exposure of particulate matter with a diameter less than or equal to 2.5 micrometers (PM2.5), and traumatic brain injury individually. For the hypothetical interventions targeting all 13 risk factors together, we found a graded increase in the PIE across frailty status.CONCLUSION: The associations between modifiable risk factors and dementia were stronger among the frail. We advocate for incorporating frailty assessments to pinpoint those most likely to benefit from targeted risk factor interventions.

  View details for DOI 10.1016/j.annepidem.2024.10.003

  View details for PubMedID 39419130

• Deprescribing of Antihypertensive Medications and Cognitive Function in Nursing Home Residents. JAMA internal medicine Jing, B., Liu, X., Graham, L. A., Dave, C. V., Li, Y., Fung, K., Liu, C. K., Abdel Magid, H. S., Growdon, M. E., Deardorff, W. J., Boscardin, W. J., Lee, S. J., Steinman, M. A., Odden, M. C. 2024

  Abstract

  Antihypertensive medication deprescribing is common among nursing home residents, yet its association with cognitive decline remains uncertain.To investigate the association of deprescribing antihypertensive medication with changes in cognitive function in nursing home residents.This cohort study using a target trial emulation approach included VA long-term care residents aged 65 years or older with stays of at least 12 weeks from 2006 to 2019. Residents who were not prescribed antihypertensive medication, with blood pressure greater than 160/90 mm Hg, or with heart failure were excluded. Eligible residents with stable medication use for 4 weeks were classified into deprescribing or stable user groups and followed for 2 years or until death or discharge for intention-to-treat (ITT) analysis. Participants switching treatment groups were censored in the per-protocol analysis. Cognitive function measurements during follow-up were analyzed using an ordinal generalized linear mixed model, adjusting for confounders with inverse probability of treatment weighting. Per-protocol analysis included inverse probability of censoring weighting. Data analyses were performed from May 1, 2023, and July 1, 2024.Deprescribing was defined as a reduction in the total number of antihypertensive medications or a decrease in medication dosage by 30%, sustained for a minimum of 2 weeks.Cognitive Function Scale (CFS) was classified as cognitively intact (CFS = 1), mildly impaired (CFS = 2), moderately impaired (CFS = 3), and severely impaired (CFS = 4).Of 45 183 long-term care residents, 12 644 residents (mean [SD] age 77.7 [8.3] years; 329 [2.6%] females and 12 315 [97.4%] males) and 12 053 residents (mean [SD] age 77.7 [8.3] years; 314 [2.6%] females and 11 739 [97.4%] males) met eligibility for ITT and per-protocol analyses, respectively. At the end of the follow-up, 12.0% of residents had a worsened CFS (higher score) and 7.7% had an improved CFS (lower score) with 10.8% of the deprescribing group and 12.1% of the stable user group showing a worsened CFS score. In the per-protocol analysis, the deprescribing group had a 12% reduction in the odds of progressing to a worse CFS category per 12-week period (odds ratio, 0.88; 95% CI, 0.78-0.99) compared to the stable user group. Among residents with dementia, deprescribing was associated with 16% reduced odds of cognitive decline (odds ratio, 0.84; 95% CI, 0.72-0.98). These patterns remained consistent in the ITT analysis.This cohort study indicates that deprescribing is associated with less cognitive decline in nursing home residents, particularly those with dementia. More data are needed to understand the benefits and harms of antihypertensive deprescribing to inform patient-centered medication management in nursing homes.

  View details for DOI 10.1001/jamainternmed.2024.4851

  View details for PubMedID 39312220

  View details for PubMedCentralID PMC11420821

• Many studies, but little certainty about the effects of statin discontinuation on outcomes. Journal of the American Geriatrics Society Odden, M. C., Dave, C. V. 2024

  View details for DOI 10.1111/jgs.19157

  View details for PubMedID 39210687

• A Polysocial Approach in Exploring Racial and Ethnic Differences in Dementia and Cognitive Decline Among U.S. Older Adults: Health and Retirement Study. Innovation in aging Ping, Y., Odden, M. C., Chen, X., Prina, M., Xu, H., Xiang, H., Wu, C. 2024; 8 (10): igae078

  Abstract

  The racial or ethnic disparity in the burden of dementia exists among older adults in the United States, whereas gaps remain in understanding the synergic effect of multiple social determinants of health on diminishing this disparity. We aim to build a polysocial score for dementia and investigate the racial or ethnic difference in dementia risk among older persons with different polysocial score categories.In this prospective cohort study, we utilized longitudinal data from the Health and Retirement Study in the United States recruiting 6 945 participants aged ≥65 years who had data on 24 social determinants of health in 2006/2008. The dementia status of participants was measured by a modified version of the Telephone Interview of Cognitive Status. The stepwise Cox regression was applied to select social determinants of health associated with incident dementia to construct a polysocial score. The multivariable Poisson model and linear mixed model were utilized to investigate the associations between polysocial score and incident dementia and cognitive decline, respectively.Eight social determinants of health were used to build the polysocial score. Non-Hispanic Black older participants had a higher incidence rate (incidence rate difference [IRD] = 22.7; 95% confident interval [95% CI] = 12.7-32.8) than non-Hispanic White older adults in the low polysocial score, while this difference was substantially attenuated in the high polysocial score category (IRD = 0.5; 95% CI = -6.4 to -7.5). The cognitive decline of non-Hispanic older Black adults with high polysocial score was 84.6% slower (averaged cognitive decline: non-Hispanic White: -2.4 [95% CI = -2.5 to -2.3] vs non-Hispanic Black: -1.3 [95% CI = -1.9 to -0.8]) than that of non-Hispanic older White persons.These findings may help comprehensively understand and address racial and ethnic disparities in dementia risk and may be integrated into existing dementia prevention programs to provide targeted interventions for community-dwelling older adults with differentiated social disadvantages.

  View details for DOI 10.1093/geroni/igae078

  View details for PubMedID 39416701

  View details for PubMedCentralID PMC11481015

• Effect of Starting Dialysis Versus Continuing Medical Management on Survival and Home Time in Older Adults With Kidney Failure : A Target Trial Emulation Study. Annals of internal medicine Montez-Rath, M. E., Thomas, I. C., Charu, V., Odden, M. C., Seib, C. D., Arya, S., Fung, E., O'Hare, A. M., Wong, S. P., Kurella Tamura, M. 2024

  Abstract

  For older adults with kidney failure who are not referred for transplant, medical management is an alternative to dialysis.To compare survival and home time between older adults who started dialysis at an estimated glomerular filtration rate (eGFR) less than 12 mL/min/1.73 m2 and those who continued medical management.Observational cohort study using target trial emulation.U.S. Department of Veterans Affairs, 2010 to 2018.Adults aged 65 years or older with chronic kidney failure and eGFR below 12 mL/min/1.73 m2 who were not referred for transplant.Starting dialysis within 30 days versus continuing medical management.Mean survival and number of days at home.Among 20 440 adults (mean age, 77.9 years [SD, 8.8]), the median time to dialysis start was 8.0 days in the group starting dialysis and 3.0 years in the group continuing medical management. Over a 3-year horizon, the group starting dialysis survived 770 days and the group continuing medical management survived 761 days (difference, 9.3 days [95% CI, -17.4 to 30.1 days]). Compared with the group continuing medical management, the group starting dialysis had 13.6 fewer days at home (CI, 7.7 to 20.5 fewer days at home). Compared with the group continuing medical management and forgoing dialysis completely, the group starting dialysis had longer survival by 77.6 days (CI, 62.8 to 91.1 days) and 14.7 fewer days at home (CI, 11.2 to 16.5 fewer days at home).Potential for unmeasured confounding due to lack of symptom assessments at eligibility; limited generalizability to women and nonveterans.Older adults starting dialysis when their eGFR fell below 12 mL/min/1.73 m2 who were not referred for transplant had modest gains in life expectancy and less time at home.U.S. Department of Veterans Affairs and National Institutes of Health.

  View details for DOI 10.7326/M23-3028

  View details for PubMedID 39159459

• Further Study Needed on Antihypertensive Medications and Fracture Risks-In Reply. JAMA internal medicine Dave, C. V., Odden, M. C. 2024

  View details for DOI 10.1001/jamainternmed.2024.3937

  View details for PubMedID 39158924

• A Counterfactual Analysis of Impact of Cesarean Birth in a First Birth on Severe Maternal Morbidity in the Subsequent Birth. Epidemiology (Cambridge, Mass.) Bane, S., Snowden, J. M., Simard, J. F., Odden, M., Kan, P., Main, E. K., Carmichael, S. L. 2024

  Abstract

  It is known that cesarean birth affects maternal outcomes in subsequent pregnancies, but specific effect estimates are lacking. We sought to quantify the effect of cesarean birth reduction among nulliparous, term, singleton, vertex (NTSV) births (i.e., preventable cesarean births) on severe maternal morbidity (SMM) in the second birth.We examined birth certificates linked with maternal hospitalization data (2007-19) from California for NTSV births with a second birth (N = 779,382). The exposure was cesarean delivery in first birth and the outcome was SMM in the second birth. We used adjusted Poisson regression models to calculate risk ratios and population attributable fraction for SMM in the second birth and conducted a counterfactual impact analysis to estimate how lowering NTSV cesarean births could reduce SMM in second birth.The adjusted risk ratio for SMM in the second birth given a prior cesarean birth was 1.7 (95% CI 1.5-1.9); 15.5% (95% CI 15.3%-15.7%) of this SMM may be attributable to prior cesarean birth. In a counterfactual analysis where 12% of the California population least likely to get a cesarean birth instead delivered vaginally, we observed 174 fewer SMM events in a population of individuals with a low-risk first birth and a subsequent birth.In our counterfactual analysis, lowering primary cesarean birth among a NTSV population was associated with fewer downstream SMM events in subsequent births and overall. Additionally, our findings reflect the importance of considering the cumulative accrual of risks across the reproductive life-course.

  View details for DOI 10.1097/EDE.0000000000001775

  View details for PubMedID 39058553

• Joint and Individual Mitochondrial DNA Variation and Cognitive Outcomes in Black and White Older Adults. The journals of gerontology. Series A, Biological sciences and medical sciences Odden, M. C., Li, Y., Jotwani, V., Dobrota, S., Tan, A., Cummings, S. R., Shlipak, M. G., Scherzer, R., Ix, J. H., Buckwalter, M., Tranah, G. J. 2024

  Abstract

  BACKGROUND: Mitochondrial dysfunction manifests in neurodegenerative diseases and other age-associated disorders. In this study, we examined variation in inherited mitochondrial DNA (mtDNA) sequences in Black and White participants from two large aging studies to identify variants related to cognitive function.METHODS: Participants included self-reported Black and White adults aged ≥ 70 years in the Lifestyle Interventions and Independence for Elders (LIFE; N=1319) and Health Aging and Body Composition (Health ABC; N=7888) studies. Cognitive function was measured by the digit-symbol substitution test (DSST), and the Modified Mini-Mental State Exam (3MSE) at baseline and over follow-up in LIFE (3.6 years) and Health ABC (10 years). We examined joint effects of multiple variants across 16 functional mitochondrial regions with cognitive function using a sequence kernel association test. Based on these results, we prioritized meta-analysis of common variants in Black and White participants using mixed effects models. A Bonferroni adjusted p-value of <0.05 was considered statistically significant.RESULTS: Joint variation in subunits ND1, ND2, and ND5 of Complex I, 12S RNA, and hypervariable region (HVR) were significantly associated with DSST and 3MSE at baseline. In meta-analyses among Black participants, variant m.4216T>C, ND1 was associated with a faster decline in 3MSE, and variant m.462C>T in the HVR was associated with a slower decline in DSST. Variant m.5460G>C, ND2 was associated with slower and m.182C>T in the HVR was associated with faster decline in 3MSE in White participants.CONCLUSION: Among Black and White adults, oxidative phosphorylation Complex I variants were associated with cognitive function.

  View details for DOI 10.1093/gerona/glae170

  View details for PubMedID 39007867

• Building an Evidence Base for Deprescribing in the Setting of Polypharmacy. JAMA network open Odden, M. C. 2024; 7 (7): e2423529

  View details for DOI 10.1001/jamanetworkopen.2024.23529

  View details for PubMedID 39078638

• Complex Patterns of Antihypertensive Treatment Changes in Long-Term Care Residents. Journal of the American Medical Directors Association Liu, X., Jing, B., Graham, L. A., Liu, C. K., Lee, S. J., Steinman, M. A., Dave, C. V., Manja, V., Li, Y., Fung, K., Odden, M. C. 2024: 105119

  Abstract

  Antihypertensive treatment changes are common in long-term care residents, yet data on the frequency and predictors of changes are lacking. We described the patterns of antihypertensive changes and examined the triggering factors.Retrospective cohort study.A total of 24,870 Department of Veterans Affairs (VA) nursing home residents ≥65 years with long-term stays (≥180 days) from 2006 to 2019.We obtained data from the VA Corporate Data Warehouse. Based on Bar Code Medication Administration medication data, we defined 2 types of change events in 180 days of admission: deprescribing (reduced number of antihypertensives or dose reduction of ≥30% compared with the previous week and maintained for at least 2 weeks) and intensification (opposite of deprescribing). Mortality was identified within 2 years after admission.More than 85% of residents were prescribed antihypertensives and 68% of them experienced ≥1 change event during the first 6 months of the nursing home stay. We categorized residents into 10 distinct patterns: no change (27%), 1 deprescribing (11%), multiple deprescribing (5%), 1 intensification (10%), multiple intensification (7%), 1 deprescribing followed by 1 intensification (3%), 1 intensification followed by 1 deprescribing (4%), 3 changes with mixed events (7%), >3 changes with mixed events (10%), and no antihypertensive use (15%). Treatment changes were more frequent in residents with better physical function and/or cognitive function. Potentially triggering factors differed by the type of antihypertensive change: incident high blood pressure and cardiovascular events were associated with intensification, and low blood pressure, weight loss, and falls were associated with deprescribing. Death occurred in 7881 (32%) residents over 2 years. The highest mortality was for those without antihypertensive medication (incidence = 344/1000 person-years).Patterns of medication changes existing in long-term care residents are complex. Future studies should explore the benefits and harms of these antihypertensive treatment changes.

  View details for DOI 10.1016/j.jamda.2024.105119

  View details for PubMedID 38950584

• Epidemiology of elective induction of labour: a timeless exposure. International journal of epidemiology Snowden, J. M., Bane, S., Osmundson, S. S., Odden, M. C., Carmichael, S. L. 2024; 53 (4)

  View details for DOI 10.1093/ije/dyae088

  View details for PubMedID 38964853

• Associations between toxicity-weighted concentrations and dementia risk: Results from the Cardiovascular Health Cognition Study. The Science of the total environment Crane, B. M., Moored, K. D., Donahue, P. T., Corrigan, A. E., Curriero, F. C., Shields, T. M., Desjardins, M. R., Richards, E. A., Rosso, A. L., Lovasi, G. S., Odden, M. C., Lopez, O. L., Biggs, M. L., Newman, A. B., Andrews, R. M., Carlson, M. C. 2024: 173706

  Abstract

  Air pollution is a modifiable risk factor for dementia. Yet, studies on specific sources of air pollution (i.e., toxic chemical emissions from industrial facilities) and dementia risk are scarce. We examined associations between toxicity-weighted concentrations of industrial pollution and dementia outcomes among a large, multi-site cohort of older adults.Participants (n = 2770) were ≥ 65 years old (Mean = 75.3, SD = 5.1 years) from the Cardiovascular Health Cognition Study (1992-1999). Toxicity-weighted concentrations were estimated using the Risk Screening Environmental Indicator (RSEI) model which incorporates total reported chemical emissions with toxicity, fate, and transport models. Estimates were aggregated to participants' baseline census tract, averaged across 1988-1992, and log2-transformed. Dementia status was clinically adjudicated in 1998-1999 and categorized by subtype (Alzheimer's, vascular, mixed). We assessed whether RSEI-estimated toxicity-weighted concentrations were associated with 1) odds of prevalent dementia and 2) incident dementia risk by subtype.After adjusting for individual and census-tract level covariates, a doubling in toxicity-weighted concentrations was associated with 9 % higher odds of prevalent dementia (OR = 1.09, 95 % CI: 1.00, 1.19). In discrete-time survival models, each doubling in toxicity-weighted concentrations was associated with a 16 % greater hazard of vascular dementia (HR = 1.16, 95 % CI: 1.01, 1.34) but was not significantly associated with all-cause, Alzheimer's disease, or mixed dementia (p's > 0.05).Living in regions with higher toxicity-weighted concentrations was associated with higher odds of prevalent dementia and a higher risk of incident vascular dementia in this large, community-based cohort of older adults. These findings support the need for additional studies to examine whether toxic chemical emissions from industrial and federal facilities may be a modifiable target for dementia prevention.

  View details for DOI 10.1016/j.scitotenv.2024.173706

  View details for PubMedID 38866169

• High Throughput Plasma Proteomics and Risk of Heart Failure and Frailty in Late Life. JAMA cardiology Ramonfaur, D., Buckley, L. F., Arthur, V., Yang, Y., Claggett, B. L., Ndumele, C. E., Walker, K. A., Austin, T., Odden, M. C., Floyd, J. S., Sanders-van Wijk, S., Njoroge, J., Kizer, J. R., Kitzman, D., Konety, S. H., Schrack, J., Liu, F., Windham, B. G., Palta, P., Coresh, J., Yu, B., Shah, A. M. 2024

  Abstract

  Heart failure (HF) and frailty frequently coexist and may share a common pathobiology, although the underlying mechanisms remain unclear. Understanding these mechanisms may provide guidance for preventing and treating both conditions.To identify shared pathways between incident HF and frailty in late life using large-scale proteomics.In this cohort study, 4877 aptamers (Somascan v4) were measured among participants in the community-based longitudinal Atherosclerosis Risk In Communities (ARIC) cohort study at visit 3 (V3; 1993-1995; n = 10 638) and at visit 5 (V5; 2011-2013; n = 3908). Analyses were externally replicated among 3189 participants in the Cardiovascular Health Study (CHS). Data analysis was conducted from February 2022 to June 2023.Protein aptamers, measured at study V3 and V5.Outcomes assessed included incident HF hospitalization after V3 and after V5, prevalent frailty at V5, and incident frailty between V5 and visit 6 (V6; 2016-2017; n = 4131). Frailty was assessed using the Fried criteria. Analyses were adjusted for age, gender, race, field center, hypertension, diabetes, smoking status, body mass index, estimated glomerular filtration rate, prevalent coronary heart disease, prevalent atrial fibrillation, and history of myocardial infarction. Mendelian randomization (MR) analysis was performed to assess potential causal effects of candidate proteins on HF and frailty.A total of 4877 protein aptamers were measured among 10 638 participants at V3 (mean [SD] age, 60 [6] years; 4886 [46%] men). Overall, 286 proteins were associated with incident HF after V3 (822 events; P < 1.0 × 10-5), 83 of which were also associated with incident after V5 (336 events; P < 1.7 × 10-4). Among HF-free participants at V5 (n = 3908; mean [SD] age, 75 [5] years; 1861 [42%] men), 48 of 83 HF-associated proteins were associated with prevalent frailty (223 cases; P < 6.0 × 10-4), 18 of which were also associated with incident frailty at V6 (152 cases; P < 1.0 × 10-3). These proteins enriched fibrosis and inflammation pathways and demonstrated stronger associations with incident HF with preserved ejection fraction (HFpEF) than HF with reduced ejection fraction. All 18 proteins were associated with both prevalent frailty and incident HF in CHS. MR identified potential causal effects of several proteins on frailty and HF.In this study, the proteins associated with risk of HF and frailty enrich for pathways related to inflammation and fibrosis as well as risk of HFpEF. Several of these proteins could potentially contribute to the shared pathophysiology of frailty and HF.

  View details for DOI 10.1001/jamacardio.2024.1178

  View details for PubMedID 38809565

• Effects of residential socioeconomic polarization on high blood pressure among nursing home residents. Health & place Abdel Magid, H. S., Jaros, S., Li, Y., Steinman, M. A., Lee, S., Peralta, C., Jing, B., Fung, K., Liu, C. K., Liu, X., Graham, L. A., Odden, M. C. 2024; 87: 103243

  Abstract

  Neighborhood concentration of racial, income, education, and housing deprivation is known to be associated with higher rates of hypertension. The objective of this study is to examine the association between tract-level spatial social polarization and hypertension in a cohort with relatively equal access to health care, a Veterans Affairs nursing home.41,973 long-term care residents aged ≥65 years were matched with tract-level Indices of Concentration at the Extremes across four socioeconomic domains. We modeled high blood pressure against these indices controlling for individual-level cardiovascular confounders.We found participants who had resided in the most disadvantaged quintile had a 1.10 (95% 1.01, 1.19) relative risk of high blood pressure compared to those in the other quintiles for the joint measuring race/ethnicity and income domain.We achieved our objective by demonstrating that concentrated deprivation is associated with worse cardiovascular outcomes even in a population with equal access to care. Measures that jointly consider economic and racial/ethnic polarization elucidate larger disparities than single domain measures.

  View details for DOI 10.1016/j.healthplace.2024.103243

  View details for PubMedID 38663339

• Preoperative GLP-1 Receptor Agonist Use and Risk of Postoperative Respiratory Complications. JAMA Dixit, A. A., Bateman, B. T., Hawn, M. T., Odden, M. C., Sun, E. C. 2024

  View details for DOI 10.1001/jama.2024.5003

  View details for PubMedID 38648036

  View details for PubMedCentralID PMC11036309

• Antihypertensive Medication and Fracture Risk in Older Veterans Health Administration Nursing Home Residents. JAMA internal medicine Dave, C. V., Li, Y., Steinman, M. A., Lee, S. J., Liu, X., Jing, B., Graham, L. A., Marcum, Z. A., Fung, K. Z., Odden, M. C. 2024

  Abstract

  Limited evidence exists on the association between initiation of antihypertensive medication and risk of fractures in older long-term nursing home residents.To assess the association between antihypertensive medication initiation and risk of fracture.This was a retrospective cohort study using target trial emulation for data derived from 29 648 older long-term care nursing home residents in the Veterans Health Administration (VA) from January 1, 2006, to October 31, 2019. Data were analyzed from December 1, 2021, to November 11, 2023.Episodes of antihypertensive medication initiation were identified, and eligible initiation episodes were matched with comparable controls who did not initiate therapy.The primary outcome was nontraumatic fracture of the humerus, hip, pelvis, radius, or ulna within 30 days of antihypertensive medication initiation. Results were computed among subgroups of residents with dementia, across systolic and diastolic blood pressure thresholds of 140 and 80 mm Hg, respectively, and with use of prior antihypertensive therapies. Analyses were adjusted for more than 50 baseline covariates using 1:4 propensity score matching.Data from 29 648 individuals were included in this study (mean [SD] age, 78.0 [8.4] years; 28 952 [97.7%] male). In the propensity score-matched cohort of 64 710 residents (mean [SD] age, 77.9 [8.5] years), the incidence rate of fractures per 100 person-years in residents initiating antihypertensive medication was 5.4 compared with 2.2 in the control arm. This finding corresponded to an adjusted hazard ratio (HR) of 2.42 (95% CI, 1.43-4.08) and an adjusted excess risk per 100 person-years of 3.12 (95% CI, 0.95-6.78). Antihypertensive medication initiation was also associated with higher risk of severe falls requiring hospitalizations or emergency department visits (HR, 1.80 [95% CI, 1.53-2.13]) and syncope (HR, 1.69 [95% CI, 1.30-2.19]). The magnitude of fracture risk was numerically higher among subgroups of residents with dementia (HR, 3.28 [95% CI, 1.76-6.10]), systolic blood pressure of 140 mm Hg or higher (HR, 3.12 [95% CI, 1.71-5.69]), diastolic blood pressure of 80 mm Hg or higher (HR, 4.41 [95% CI, 1.67-11.68]), and no recent antihypertensive medication use (HR, 4.77 [95% CI, 1.49-15.32]).Findings indicated that initiation of antihypertensive medication was associated with elevated risks of fractures and falls. These risks were numerically higher among residents with dementia, higher baseline blood pressures values, and no recent antihypertensive medication use. Caution and additional monitoring are advised when initiating antihypertensive medication in this vulnerable population.

  View details for DOI 10.1001/jamainternmed.2024.0507

  View details for PubMedID 38648065

  View details for PubMedCentralID PMC11036308

• Use of natural language processing method to identify regional anesthesia from clinical notes. Regional anesthesia and pain medicine Graham, L. A., Illarmo, S. S., Wren, S. M., Odden, M. C., Mudumbai, S. C. 2024

  Abstract

  INTRODUCTION: Accurate data capture is integral for research and quality improvement efforts. Unfortunately, limited guidance for defining and documenting regional anesthesia has resulted in wide variation in documentation practices, even within individual hospitals, which can lead to missing and inaccurate data. This cross-sectional study sought to evaluate the performance of a natural language processing (NLP)-based algorithm developed to identify regional anesthesia within unstructured clinical notes.METHODS: We obtained postoperative clinical notes for all patients undergoing elective non-cardiac surgery with general anesthesia at one of six Veterans Health Administration hospitals in California between January 1, 2017, and December 31, 2022. After developing and executing our algorithm, we compared our results to a frequently used referent, the Corporate Data Warehouse structured data, to assess the completeness and accuracy of the currently available data. Measures of agreement included sensitivity, positive predictive value, false negative rate, and accuracy.RESULTS: We identified 27,713 procedures, of which 9310 (33.6%) received regional anesthesia. 96.6% of all referent regional anesthesia cases were identified in the clinic notes with a very low false negative rate and good accuracy (false negative rate=0.8%, accuracy=82.5%). Surprisingly, the clinic notes documented more than two times the number of regional anesthesia cases that were documented in the referent (algorithm n=9154vs referent n=4606).DISCUSSION: While our algorithm identified nearly all regional anesthesia cases from the referent, it also identified more than two times as many regional anesthesia cases as the referent, raising concerns about the accuracy and completeness of regional anesthesia documentation in administrative and clinical databases. We found that NLP was a promising alternative for identifying clinical information when existing databases lack complete documentation.

  View details for DOI 10.1136/rapm-2024-105340

  View details for PubMedID 38580338

• Representation of Real-World Adults With Chronic Kidney Disease in Clinical Trials Supporting Blood Pressure Treatment Targets. Journal of the American Heart Association Li, J., An, J., Huang, M., Zhou, M., Montez-Rath, M. E., Niu, F., Sim, J. J., Pao, A. C., Charu, V., Odden, M. C., Kurella Tamura, M. 2024: e031742

  Abstract

  Little is known about how well trial participants with chronic kidney disease (CKD) represent real-world adults with CKD. We assessed the population representativeness of clinical trials supporting the 2021 Kidney Disease: Improving Global Outcomes blood pressure (BP) guidelines in real-world adults with CKD.Using a cross-sectional analysis, we identified patients with CKD who met the guideline definition of hypertension based on use of antihypertensive medications or sustained systolic BP ≥120 mm Hg in 2019 in the Veterans Affairs and Kaiser Permanente of Southern California. We applied the eligibility criteria from 3 BP target trials, SPRINT (Systolic Pressure Intervention Trial), ACCORD (Action to Control Cardiovascular Risk in Diabetes), and AASK (African American Study of Kidney Disease), to estimate the proportion of adults with a systolic BP above the guideline-recommended target and the proportion who met eligibility criteria for ≥1 trial. We identified 503 480 adults in the Veterans Affairs and 73 412 adults in Kaiser Permanente of Southern California with CKD and hypertension in 2019. We estimated 79.7% in the Veterans Affairs and 87.3% in the Kaiser Permanente of Southern California populations had a systolic BP ≥120 mm Hg; only 23.8% [23.7%-24.0%] in the Veterans Affairs and 20.8% [20.5%-21.1%] in Kaiser Permanente of Southern California were trial-eligible. Among trial-ineligible patients, >50% met >1 exclusion criteria.Major BP target trials were representative of fewer than 1 in 4 real-world adults with CKD and hypertension. A large proportion of adults who are at risk for cardiovascular morbidity from hypertension and susceptible to adverse treatment effects lack relevant treatment information.

  View details for DOI 10.1161/JAHA.123.031742

  View details for PubMedID 38533947

• Plasma proteomic signature of human longevity. Aging cell Liu, X., Axelsson, G. T., Newman, A. B., Psaty, B. M., Boudreau, R. M., Wu, C., Arnold, A. M., Aspelund, T., Austin, T. R., Gardin, J. M., Siggeirsdottir, K., Tracy, R. P., Gerszten, R. E., Launer, L. J., Jennings, L. L., Gudnason, V., Sanders, J. L., Odden, M. C. 2024: e14136

  Abstract

  The identification of protein targets that exhibit anti-aging clinical potential could inform interventions to lengthen the human health span. Most previous proteomics research has been focused on chronological age instead of longevity. We leveraged two large population-based prospective cohorts with long follow-ups to evaluate the proteomic signature of longevity defined by survival to 90 years of age. Plasma proteomics was measured using a SOMAscan assay in 3067 participants from the Cardiovascular Health Study (discovery cohort) and 4690 participants from the Age Gene/Environment Susceptibility-Reykjavik Study (replication cohort). Logistic regression identified 211 significant proteins in the CHS cohort using a Bonferroni-adjusted threshold, of which 168 were available in the replication cohort and 105 were replicated (corrected p value <0.05). The most significant proteins were GDF-15 and N-terminal pro-BNP in both cohorts. A parsimonious protein-based prediction model was built using 33 proteins selected by LASSO with 10-fold cross-validation and validated using 27 available proteins in the validation cohort. This protein model outperformed a basic model using traditional factors (demographics, height, weight, and smoking) by improving the AUC from 0.658 to 0.748 in the discovery cohort and from 0.755 to 0.802 in the validation cohort. We also found that the associations of 169 out of 211 proteins were partially mediated by physical and/or cognitive function. These findings could contribute to the identification of biomarkers and pathways of aging and potential therapeutic targets to delay aging and age-related diseases.

  View details for DOI 10.1111/acel.14136

  View details for PubMedID 38440820

• Evaluating the Sick Quitting Hypothesis for Frailty Status and Reducing Alcohol Use Among People With HIV in a Longitudinal Clinical Cohort Study. The Journal of the Association of Nurses in AIDS Care : JANAC Ruderman, S. A., Drumright, L. N., Delaney, J. A., Webel, A. R., Fitzpatrick, A. L., Whitney, B. M., Nance, R. M., Hahn, A. W., Ma, J., Mixson, L. S., Eltonsy, S., Willig, A. L., Mayer, K. H., Napravnik, S., Greene, M., McCaul, M., Cachay, E., Kritchevsky, S. B., Austad, S. N., Landay, A., Saag, M. S., Kitahata, M. M., Lau, B., Lesko, C., Chander, G., Crane, H. M., Odden, M. C. 2023; 35 (1): e1-e2

  Abstract

  “Sick quitting”, a phenomenon describing reductions in alcohol consumption following poor health, may explain observations that alcohol appears protective for frailty risk. We examined associations between frailty and reductions in drinking frequency among people with HIV (PWH). At six Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) sites between January 2012 and August 2021, we assessed whether frailty, measured via validated modified frailty phenotype, precedes reductions in drinking frequency. We associated time-updated frailty with quitting and reducing frequency of any drinking and heavy episodic drinking (HED), adjusted for demographic and clinical characteristics in Cox models. Among 5,654 PWH reporting drinking, 60% reported >monthly drinking and 18% reported ≥monthly HED. Over an average of 5.4 years, frail PWH had greater probabilities of quitting (HR:1.56, 95%CI:1.13–2.15) and reducing (HR:1.35, 95%CI:1.13–1.62) drinking frequency, as well as reducing HED frequency (HR:1.58, 95%CI:1.20–2.09) vs. robust PWH. Sick quitting likely confounds the association between alcohol use and frailty risk, requiring investigation for control.

  View details for DOI 10.1097/JNC.0000000000000445

  View details for PubMedID 38150573

  View details for PubMedCentralID PMC10753926

• Evaluating the Sick Quitting Hypothesis for Frailty Status and Reducing Alcohol Use Among People With HIV in a Longitudinal Clinical Cohort Study. The Journal of the Association of Nurses in AIDS Care : JANAC Ruderman, S. A., Drumright, L. N., Delaney, J. A., Webel, A. R., Fitzpatrick, A. L., Whitney, B. M., Nance, R. M., Hahn, A. W., Ma, J., Mixson, L. S., Eltonsy, S., Willig, A. L., Mayer, K. H., Napravnik, S., Greene, M., McCaul, M., Cachay, E., Kritchevsky, S. B., Austad, S. N., Landay, A., Saag, M. S., Kitahata, M. M., Lau, B., Lesko, C., Chander, G., Crane, H. M., Odden, M. C. 2023; 35 (1): 5-16

  Abstract

  "Sick quitting," a phenomenon describing reductions in alcohol consumption following poor health, may explain observations that alcohol appears protective for frailty risk. We examined associations between frailty and reductions in drinking frequency among people with HIV (PWH). At six Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) sites between January 2012 and August 2021, we assessed whether frailty, measured through validated modified frailty phenotype, precedes reductions in drinking frequency. We associated time-updated frailty with quitting and reducing frequency of any drinking and heavy episodic drinking (HED), adjusted for demographic and clinical characteristics in Cox models. Among 5,654 PWH reporting drinking, 60% reported >monthly drinking and 18% reported ≥monthly HED. Over an average of 5.4 years, frail PWH had greater probabilities of quitting (HR: 1.56, 95% confidence interval [95% CI] [1.13-2.15]) and reducing (HR: 1.35, 95% CI [1.13-1.62]) drinking frequency, as well as reducing HED frequency (HR: 1.58, 95% CI [1.20-2.09]) versus robust PWH. Sick quitting likely confounds the association between alcohol use and frailty risk, requiring investigation for control.

  View details for DOI 10.1097/JNC.0000000000000441

  View details for PubMedID 38150572

• Association between antihypertensive medication initiation and risk of fractures among older adults in VA long-term care facilities Dave, C., Li, Y., Odden, M. WILEY. 2023: 27-28

  View details for Web of Science ID 001091511700048

• Neighborhood factors and survival to old age: The Jackson Heart Study. Preventive medicine reports Odden, M. C., Li, Y., Thorpe, R. J., Tan, A., Sims, K. D., Ratcliff, J., Abdel Magid, H. S., Sims, M. 2023; 35: 102360

  Abstract

  Few studies have evaluated environmental factors that predict survival to old age. Our study included 913 African American participants in the Jackson Heart Study (JHS) who resided in the tri-county area of the Jackson, MS metropolitan area and were 65-80 years at baseline. Participants were followed from 2000 through 2019 for the outcome of survival to 85 years old. We evaluated each of the following census tract-level measures of the social/physical environment as exposures: socioeconomic status, cohesion, violence, disorder, healthy food stores, residential land use, and walkability. We assessed mediation by physical activity and chronic conditions. As a complementary ecologic analysis, we used census-tract data to examine factors associated with a greater life expectancy. A total of 501 (55%) JHS participants survived to age 85 years or older. Higher social cohesion and greater residential land use were modestly associated with survival to old age (risk difference = 25%, 95% CI: 0-49%; and 4%, 95% CI: 1-7%, respectively). These neighborhood effects were modestly mediated through leisure time physical activity; additionally, social cohesion was mediated through home and yard activity. In our ecologic analysis, a greater percentage of homeowners and a greater proportion of people living in partnered families were associated with higher census-tract level life expectancy. African American older adults living in residential neighborhoods or neighborhoods with high social cohesion were more likely to survive to old age.

  View details for DOI 10.1016/j.pmedr.2023.102360

  View details for PubMedID 37588880

  View details for PubMedCentralID PMC10425932

• Treatment and Control of Hypertension Among Adults With Chronic Kidney Disease, 2011 to 2019. Hypertension (Dallas, Tex. : 1979) Martinez, J. D., Thomas, I. C., Montez-Rath, M. E., Pao, A. C., Fung, E., Charu, V., Sim, J. J., An, J., Odden, M. C., Kurella Tamura, M. 2023

  Abstract

  Hypertension frequently accompanies chronic kidney disease (CKD) as etiology and sequela. We examined contemporary trends in hypertension treatment and control in a national sample of adults with CKD.We evaluated 5% cross-sectional samples of adults with CKD between 2011 and 2019 in the Veterans Health Administration. We defined CKD as a sustained estimated glomerular filtration rate value <60 mL/min per 1.73 m2 or a urine albumin-to-creatinine ratio ≥30 mg/g. The main outcomes were blood pressure (BP) control, defined as a systolic BP <140 mm Hg and a diastolic BP <90 mm Hg based on the mean of monthly BP measurements, and prescriptions for antihypertensive medications.The annual samples ranged between n=22 110 and n=33 039 individuals, with a mean age of 72 years, 96% of whom were male. Between 2011 and 2014, the age-adjusted proportion of adults with controlled BP declined from 78.0% to 72.2% (P value for linear trend, <0.001), reached a nadir of 71.0% in 2015, and then increased to 72.9% by 2019 (P value for linear trend, <0.001). Among adults with BP above goal, the age-adjusted proportion who did not receive antihypertensive treatment increased throughout the decade from 18.8% to 21.6%, and the age-adjusted proportion who received ≥3 antihypertensive medications decreased from 41.8% to 36.3%. Prescriptions for first-line antihypertensive agents also decreased.Among adults with CKD treated in the Veterans Health Administration, the proportion with controlled BP declined between 2011 and 2015 followed by a modest increase, coinciding with fewer prescriptions for antihypertensive medications.

  View details for DOI 10.1161/HYPERTENSIONAHA.123.21523

  View details for PubMedID 37706307

• Late-life plasma proteins associated with prevalent and incident frailty: A proteomic analysis. Aging cell Liu, F., Austin, T. R., Schrack, J. A., Chen, J., Walston, J., Mathias, R. A., Grams, M., Odden, M. C., Newman, A., Psaty, B. M., Ramonfaur, D., Shah, A. M., Windham, B. G., Coresh, J., Walker, K. A. 2023

  Abstract

  Proteomic approaches have unique advantages in the identification of biological pathways that influence physical frailty, a multifactorial geriatric syndrome predictive of adverse health outcomes in older adults. To date, proteomic studies of frailty are scarce, and few evaluated prefrailty as a separate state or examined predictors of incident frailty. Using plasma proteins measured by 4955 SOMAmers in the Atherosclerosis Risk in Community study, we identified 134 and 179 proteins cross-sectionally associated with prefrailty and frailty, respectively, after Bonferroni correction (p < 1 × 10-5 ) among 3838 older adults aged ≥65 years, adjusting for demographic and physiologic factors and chronic diseases. Among them, 23 (17%) and 82 (46%) were replicated in the Cardiovascular Health Study using the same models (FDR p < 0.05). Notably, higher odds of prefrailty and frailty were observed with higher levels of growth differentiation factor 15 (GDF15; pprefrailty  = 1 × 10-15 , pfrailty  = 2 × 10-19 ), transgelin (TAGLN; pprefrailty  = 2 × 10-12 , pfrailty  = 6 × 10-22 ), and insulin-like growth factor-binding protein 2 (IGFBP2; pprefrailty  = 5 × 10-15 , pfrailty  = 1 × 10-15 ) and with a lower level of growth hormone receptor (GHR, pprefrailty  = 3 × 10-16 , pfrailty  = 2 × 10-18 ). Longitudinally, we identified 4 proteins associated with incident frailty (p < 1 × 10-5 ). Higher levels of triggering receptor expressed on myeloid cells 1 (TREM1), TAGLN, and heart and adipocyte fatty-acid binding proteins predicted incident frailty. Differentially regulated proteins were enriched in pathways and upstream regulators related to lipid metabolism, angiogenesis, inflammation, and cell senescence. Our findings provide a set of plasma proteins and biological mechanisms that were dysregulated in both the prodromal and the clinical stage of frailty, offering new insights into frailty etiology and targets for intervention.

  View details for DOI 10.1111/acel.13975

  View details for PubMedID 37697678

• Neighborhood Characteristics and Elevated Blood Pressure in Older Adults. JAMA network open Sims, K. D., Willis, M. D., Hystad, P. W., Batty, G. D., Bibbins-Domingo, K., Smit, E., Odden, M. C. 2023; 6 (9): e2335534

  Abstract

  The local environment remains an understudied contributor to elevated blood pressure among older adults. Untargeted approaches can identify neighborhood conditions interrelated with racial segregation that drive hypertension disparities.To evaluate independent associations of sociodemographic, economic, and housing neighborhood factors with elevated blood pressure.In this cohort study, the sample included Health and Retirement Study participants who had between 1 and 3 sets of biennial sphygmomanometer readings from 2006 to 2014 or 2008 to 2016. Statistical analyses were conducted from February 5 to November 30, 2021.Fifty-one standardized American Community Survey census tract variables (2005-2009).Elevated sphygmomanometer readings over the study period (6-year period prevalence): a value of at least 140 mm Hg for systolic blood pressure and/or at least 90 mm Hg for diastolic blood pressure. Participants were divided 50:50 into training and test data sets. Generalized estimating equations were used to summarize multivariable associations between each neighborhood variable and the period prevalence of elevated blood pressure, adjusting for individual-level covariates. Any neighborhood factor associated (Simes-adjusted for multiple comparisons P ≤ .05) with elevated blood pressure in the training data set was rerun in the test data set to gauge model performance. Lastly, in the full cohort, race- and ethnicity-stratified associations were evaluated for each identified neighborhood factor on the likelihood of elevated blood pressure.Of 12 946 participants, 4565 (35%) had elevated sphygmomanometer readings (median [IQR] age, 68 [63-73] years; 2283 [50%] male; 228 [5%] Hispanic or Latino, 502 [11%] non-Hispanic Black, and 3761 [82%] non-Hispanic White). Between 2006 and 2016, a lower likelihood of elevated blood pressure was observed (relative risk for highest vs lowest tertile, 0.91; 95% CI, 0.86-0.96) among participants residing in a neighborhood with recent (post-1999) in-migration of homeowners. This association was precise among participants with non-Hispanic White and other race and ethnicity (relative risk, 0.91; 95% CI, 0.85-0.97) but not non-Hispanic Black participants (relative risk, 0.97; 95% CI, 0.85-1.11; P = .48 for interaction) or Hispanic or Latino participants (relative risk, 0.84; 95% CI, 0.65-1.09; P = .78 for interaction).In this cohort study of older adults, recent relocation of homeowners to a neighborhood was robustly associated with reduced likelihood of elevated blood pressure among White participants but not their racially and ethnically marginalized counterparts. Our findings indicate that gentrification may influence later-life blood pressure control.

  View details for DOI 10.1001/jamanetworkopen.2023.35534

  View details for PubMedID 37747730

• Serum NfL and GFAP are associated with incident dementia and dementia mortality in older adults: The cardiovascular health study. Alzheimer's & dementia : the journal of the Alzheimer's Association Cronjé, H. T., Liu, X., Odden, M. C., Moseholm, K. F., Seshadri, S., Satizabal, C. L., Lopez, O. L., Bis, J. C., Djoussé, L., Fohner, A. E., Psaty, B. M., Tracy, R. P., Longstreth, W. T., Jensen, M. K., Mukamal, K. J. 2023

  Abstract

  Circulating neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have been independently associated with dementia risk. Their additive association, and their associations with dementia-specific mortality, have not been investigated.We associated serum NfL, GFAP, total tau ,and ubiquitin carboxyl-terminal hydrolase-L1, measured in 1712 dementia-free adults, with 19-year incident dementia and dementia-specific mortality risk, and with 3-year cognitive decline.In adjusted models, being in the highest versus lowest tertile of NfL or GFAP associated with a hazard ratio (HR) of 1.49 (1.20-1.84) and 1.38 (1.15-1.66) for incident dementia, and 2.87 (1.79-4.61) and 2.76 (1.73-4.40) for dementia-specific mortality. Joint third versus first tertile exposure further increased risk; HR = 2.06 (1.60-2.67) and 9.22 (4.48-18.9). NfL was independently associated with accelerated cognitive decline.Circulating NfL and GFAP may, independently and jointly, provide useful clinical insight regarding dementia risk and prognosis.

  View details for DOI 10.1002/alz.13367

  View details for PubMedID 37392405

• Tobacco Smoking and Pack-years are Associated with Frailty Among People with HIV. Journal of acquired immune deficiency syndromes (1999) Ruderman, S. A., Odden, M. C., Webel, A. R., Fitzpatrick, A. L., Crane, P. K., Nance, R. M., Drumright, L. N., Whitney, B. M., Mixson, L. S., Ma, J., Willig, A. L., Haidar, L., Eltonsy, S., Mayer, K. H., O'Cleirigh, C., Cropsey, K. L., Eron, J. J., Napravnik, S., Greene, M., McCaul, M., Chander, G., Cachay, E., Lober, W. B., Kritchevsky, S. B., Austad, S., Landay, A., Pandya, C., Cartujano-Barrera, F., Saag, M. S., Kamen, C., Hahn, A. W., Kitahata, M. M., Delaney, J. A., Crane, H. M. 2023

  Abstract

  Tobacco smoking increases frailty risk among the general population and is common among people with HIV (PWH), who experience higher rates of frailty at earlier ages than the general population.We identified 8,608 PWH across 6 Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) sites who completed ≥2 patient-reported outcome assessments, including a frailty phenotype measuring unintentional weight loss, poor mobility, fatigue, and inactivity, scored 0-4. Smoking was measured as baseline pack-years and time-updated never, former, or current use with cigarettes/day. We used Cox models to associate smoking with risk of incident frailty (score ≥3) and deterioration (frailty score increase by ≥2 points), adjusted for demographics, antiretroviral medication, and time-updated CD4 count.Mean follow-up of PWH was 5.3 years (median: 5.0), the mean age at baseline was 45 years, 15% were female, and 52% were non-White. At baseline, 60% reported current or former smoking. Current (HR: 1.79; 95%CI: 1.54-2.08) and former (HR: 1.31; 95%CI: 1.12-1.53) smoking were associated with higher incident frailty risk, as was higher pack-years. Current smoking (among younger PWH) and pack-years, but not former smoking, were associated with higher risk of deterioration.Among PWH, smoking status and duration are associated with incident and worsening frailty.

  View details for DOI 10.1097/QAI.0000000000003242

  View details for PubMedID 37368939

• The Association of Intensive Blood Pressure Treatment and Non-Fatal Cardiovascular or Serious Adverse Events in Older Adults with Mortality: Mediation Analysis in SPRINT. European journal of preventive cardiology Krishnaswami, A., Rich, M. W., Kwak, M. J., Goyal, P., Forman, D. E., Damluji, A. A., Solomon, M., Rana, J. S., Kado, D. M., Odden, M. C. 2023

  Abstract

  Randomized clinical trials of hypertension treatment intensity evaluate effects on incident major adverse cardiovascular events (MACE) and serious adverse events (SAE). Occurrences after a non-fatal index event have not been rigorously evaluated. The current aim was to evaluate the association of intensive (<120 mmHg) to standard (<140 mmHg) blood pressure treatment to mortality mediated through a non-fatal MACE or non-fatal SAE in 9,361 Systolic Blood Pressure Intervention trial participants.Logistic regression and causal mediation modeling to obtain direct and mediated effects of intensive BP treatment. Primary outcome was all-cause mortality (ACM). Secondary outcomes were cardiovascular (CVM) and non-CV mortality (non-CVM).The direct effect of intensive treatment was a lowering of ACM [OR 0.75, 0.60-0.94]. The MACE-mediated effect substantially attenuated [OR 0.96, 0.92-0.99] ACM; while the SAE-mediated effect was associated with increased [OR 1.03, 1.01-1.05] ACM. Similar patterns were noted for intensive BP treatment on CVM and non-CVM. We also noted the SAE incidence was 3.9-fold higher than MACE incidence (13.7% vs 3.5%), and there was a total of 365 (3.9%) ACM with non-CVM 2.6-fold higher than CVM [2.81% (263/9,361) vs 1.09% (102/9,361)]. The SAE to MACE and non-CVM to CVM preponderance was across all age-groups with the ≥ 80-year age group having the highest differences.The current analytic techniques demonstrated that intensive BP treatment was associated with an attenuated mortality benefit when MACE-mediated and possibly harmful when SAE-mediated. Current cardiovascular trial reporting of treatment effects does not allow expansion of the lens to focus on important occurrences after the index event.

  View details for DOI 10.1093/eurjpc/zwad132

  View details for PubMedID 37185634

• Regression discontinuity design to evaluate the effect of statins on myocardial infarction in electronic health records. European journal of epidemiology Odden, M. C., Zhang, A., Jawadekar, N., Tan, A., Moran, A. E., Glymour, M. M., Brayne, C., Zeki Al Hazzouri, A., Calonico, S. 2023

  Abstract

  Regression discontinuity design (RDD) is a quasi-experimental method intended for causal inference in observational settings. While RDD is gaining popularity in clinical studies, there are limited real-world studies examining the performance on estimating known trial casual effects. The goal of this paper is to estimate the effect of statins on myocardial infarction (MI) using RDD and compare with propensity score matching and Cox regression. For the RDD, we leveraged a 2008 UK guideline that recommends statins if a patient's 10-year cardiovascular disease (CVD) risk score>20%. We used UK electronic health record data from the Health Improvement Network on 49,242 patients aged 65+in 2008-2011 (baseline) without a history of CVD and no statin use in the two years prior to the CVD risk score assessment. Both the regression discontinuity (n=19,432) and the propensity score matched populations (n=24,814) demonstrated good balance of confounders. Using RDD, the adjusted point estimate for statins on MI was in the protective direction and similar to the statin effect observed in clinical trials, although the confidence interval included the null (HR=0.8, 95% CI 0.4, 1.4). Conversely, the adjusted estimates using propensity score matching and Cox regression remained in the harmful direction: HR=2.42 (95% CI 1.96, 2.99) and 2.51 (2.12, 2.97). RDD appeared superior to other methods in replicating the known protective effect of statins with MI, although precision was poor. Our findings suggest that, when used appropriately, RDD can expand the scope of clinical investigations aimed at causal inference by leveraging treatment rules from everyday clinical practice.

  View details for DOI 10.1007/s10654-023-00982-w

  View details for PubMedID 36935439

• Systolic blood pressure, antihypertensive treatment, and cardiovascular and mortality risk in VA nursing home residents. Journal of the American Geriatrics Society Liu, X., Steinman, M. A., Lee, S. J., Peralta, C. A., Graham, L. A., Li, Y., Jing, B., Fung, K. Z., Odden, M. C. 2023

  Abstract

  Optimal systolic BP (SBP) control in nursing home residents is uncertain, largely because this population has been excluded from clinical trials. We examined the association of SBP levels with the risk of cardiovascular (CV) events and mortality in Veterans Affairs (VA) nursing home residents on different numbers of antihypertensive medications.Our study included 36,634 residents aged ≥65 years with a VA nursing home stay of ≥90 days from October 2006-June 2019. SBP was averaged over the first week after admission and divided into categories. Cause-specific hazard ratios (HRs) of SBP categories with CV events (primary outcome) and all-cause mortality (secondary outcome) were examined using Cox regression and multistate modeling stratified by the number of antihypertensive medications used at admission (0, 1 or 2, and ≥3 medications).More than 76% of residents were on antihypertensive therapy and 20% received ≥3 medications. In residents on antihypertensive therapy, a low SBP < 110 mmHg (compared with SBP 130 ~ 149 mmHg) was associated with a greater CV risk (adjusted HR [95% confidence interval]: 1.47 [1.28-1.68] in 1 or 2 medications group, and 1.41 [1.19-1.67] in ≥3 medications group). In residents on no antihypertensives, both low SBP < 110 mmHg and high SBP ≥ 150 mmHg were associated with higher mortality; while in residents receiving any antihypertensives, a low SBP was associated with higher mortality and the highest point estimates were for SBP < 110 mmHg (1.36 [1.28-1.45] in 1 or 2 medications group, and 1.47 [1.31-1.64] in ≥3 medications group).The associations of SBP with CV and mortality risk varied by the intensity of antihypertensive treatment among VA nursing home residents. A low SBP among those receiving antihypertensives was associated with increased CV and mortality risk, and untreated high SBP was associated with higher mortality. More research is needed on the benefits and harms of SBP lowering in long-term care populations.

  View details for DOI 10.1111/jgs.18301

  View details for PubMedID 36826917

• Practical Guide to Honest Causal Forests for Identifying Heterogeneous Treatment Effects. American journal of epidemiology Jawadekar, N., Kezios, K., Odden, M. C., Stingone, J. A., Calonico, S., Rudolph, K., Al Hazzouri, A. Z. 2023

  Abstract

  "Heterogeneous treatment effects" is a term which refers to conditional average treatment effects (i.e., CATEs) that vary across population subgroups. Epidemiologists are often interested in estimating such effects because they can help detect populations who may particularly benefit from or be harmed by a treatment. However, standard regression approaches for estimating heterogeneous effects are limited by pre-existing hypotheses, test a single effect modifier at a time, and are subject to the multiple comparisons problem. The objective of this text is to offer a practical guide to honest causal forests, an ensemble tree-based learning method which can discover as well as estimate heterogeneous treatment effects using a data-driven approach. We discuss the fundamentals of tree-based methods, describe how honest causal forests can identify and estimate heterogeneous effects, and demonstrate an implementation of this method using simulated data. Our implementation highlights the steps required to simulate datasets, build honest causal forests, and assess model performance across a variety of simulation scenarios. Overall, this paper is intended for epidemiologists and other population health researchers who lack an extensive background in machine learning yet are interested in utilizing an emerging method for identifying and estimating heterogeneous treatment effects.

  View details for DOI 10.1093/aje/kwad043

  View details for PubMedID 36843042

• Validity Properties of a Self-reported Modified Frailty Phenotype Among People With HIV in Clinical Care in the United States. The Journal of the Association of Nurses in AIDS Care : JANAC Ruderman, S. A., Webel, A. R., Willig, A. L., Drumright, L. N., Fitzpatrick, A. L., Odden, M. C., Cleveland, J. D., Burkholder, G., Davey, C. H., Fleming, J., Buford, T. W., Jones, R., Nance, R. M., Whitney, B. M., Mixson, L. S., Hahn, A. W., Mayer, K. H., Greene, M., Saag, M. S., Kamen, C., Pandya, C., Lober, W. B., Kitahata, M. M., Crane, P. K., Crane, H. M., Delaney, J. A. 2023

  Abstract

  ABSTRACT: Modifications to Fried's frailty phenotype (FFP) are common. We evaluated a self-reported modified frailty phenotype (Mod-FP) used among people with HIV (PWH). Among 522 PWH engaged in two longitudinal studies, we assessed validity of the four-item Mod-FP compared with the five-item FFP. We compared the phenotypes via receiver operator characteristic curves, agreement in classifying frailty, and criterion validity via association with having experienced falls. Mod-FP classified 8% of PWH as frail, whereas FFP classified 9%. The area under the receiver operator characteristic curve for Mod-FP classifying frailty was 0.93 (95% CI = 0.91-0.96). We observed kappa ranging from 0.64 (unweighted) to 0.75 (weighted) for categorizing frailty status. Both definitions found frailty associated with a greater odds of experiencing a fall; FFP estimated a slightly greater magnitude (i.e., OR) for the association than Mod-FP. The Mod-FP has good performance in measuring frailty among PWH and is reasonable to use when the gold standards of observed assessments (i.e., weakness and slowness) are not feasible.

  View details for DOI 10.1097/JNC.0000000000000389

  View details for PubMedID 36652200

• Racial and ethnic disparities in years of potential life loss among patients with cirrhosis during the COVID-19 pandemic in the United States. The American journal of gastroenterology Zhao, Y., Yeo, Y. H., Samaan, J., Lv, F., He, X., Liu, J., Li, M., Gao, N., Park, J., Yang, J. D., Ayoub, W. S., Zhang, L., Odden, M. C., Ji, F., Nguyen, M. H. 2023

  View details for DOI 10.14309/ajg.0000000000002191

  View details for PubMedID 36728136

• Scientific opportunities in resilience research for cardiovascular health and wellness. Report from a National Heart, Lung, and Blood Institute workshop. FASEB journal : official publication of the Federation of American Societies for Experimental Biology Taylor, H. A., Finkel, T., Gao, Y., Ballinger, S. W., Campo, R., Chen, R., Chen, S. H., Davidson, K., Iruela-Arispe, M. L., Jaquish, C., LeBrasseur, N. K., Odden, M. C., Papanicolaou, G. J., Picard, M., Srinivas, P., Tjurmina, O., Wolz, M., Galis, Z. S. 2022; 36 (12): e22639

  Abstract

  Exposure of biological systems to acute or chronic insults triggers a host of molecular and physiological responses to either tolerate, adapt, or fully restore homeostasis; these responses constitute the hallmarks of resilience. Given the many facets, dimensions, and discipline-specific focus, gaining a shared understanding of "resilience" has been identified as a priority for supporting advances in cardiovascular health. This report is based on the working definition: "Resilience is the ability of living systems to successfully maintain or return to homeostasis in response to physical, molecular, individual, social, societal, or environmental stressors or challenges," developed after considering many factors contributing to cardiovascular resilience through deliberations of multidisciplinary experts convened by the National Heart, Lung, and Blood Institute during a workshop entitled: "Enhancing Resilience for Cardiovascular Health and Wellness." Some of the main emerging themes that support the possibility of enhancing resilience for cardiovascular health include optimal energy management and substrate diversity, a robust immune system that safeguards tissue homeostasis, and social and community support. The report also highlights existing research challenges, along with immediate and long-term opportunities for resilience research. Certain immediate opportunities identified are based on leveraging existing high-dimensional data from longitudinal clinical studies to identify vascular resilience measures, create a 'resilience index,' and adopt a life-course approach. Long-term opportunities include developing quantitative cell/organ/system/community models to identify resilience factors and mechanisms at these various levels, designing experimental and clinical interventions that specifically assess resilience, adopting global sharing of resilience-related data, and cross-domain training of next-generation researchers in this field.

  View details for DOI 10.1096/fj.202201407R

  View details for PubMedID 36322029

• Variation in Initial and Continued use of Primary, Mental Health, and Specialty Video Care among Veterans. Health services research Ferguson, J. M., Wray, C. M., Jacobs, J., Greene, L., Wagner, T. H., Odden, M. C., Freese, J., Van Campen, J., Asch, S. M., Heyworth, L., Zulman, D. M. 2022

  Abstract

  OBJECTIVE: To identify which Veteran populations are routinely accessing video-based care.DATA SOURCES AND STUDY SETTING: National, secondary administrative data from electronic health records at the Veterans Health Administration (VHA), 2019-2021 STUDY DESIGN: This retrospective cohort analysis identified patient characteristics associated with the odds of using any video care; and then, among those with a previous video visit, the annual rate of video care utilization. Video care use was reported overall and stratified into care type (e.g., primary, mental health, and specialty video care) between March 10, 2020 and February 28, 2021.DATA COLLECTION: Veterans active in VA health care (>1 outpatient visit between March 11, 2019 and March 10, 2020) were included in this study.PRINCIPAL FINDINGS: Among 5,389,129 Veterans in this evaluation, approximately 27.4% of Veterans had at least one video visit. We found differences in video care utilization by type of video care: 14.7% of Veterans had at least one primary care video visit, 10.6% a mental health video visit, and 5.9% a specialty care video visit. Veterans with a history of housing instability had a higher overall rate of video care driven by their higher usage of video for mental health care compared with Veterans in stable housing. American Indian/Alaska Native Veterans had reduced odds of video visits, yet similar rates of video care when compared to White Veterans. Low-income Veterans had lower odds of using primary video care yet slightly elevated rates of primary video care among those with at least one video visit when compared to Veterans enrolled at VA without special considerations.CONCLUSIONS: Variation in video care utilization patterns by type of care identified Veteran populations that might require greater resources and support to initiate and sustain video care use. Our data support service specific outreach to homeless and American Indian/Alaska Native Veterans.

  View details for DOI 10.1111/1475-6773.14098

  View details for PubMedID 36345235

• Plasma proteomic signature of decline in gait speed and grip strength. Aging cell Liu, X., Pan, S., Xanthakis, V., Vasan, R. S., Psaty, B. M., Austin, T. R., Newman, A. B., Sanders, J. L., Wu, C., Tracy, R. P., Gerszten, R. E., Odden, M. C. 2022: e13736

  Abstract

  The biological mechanisms underlying decline in physical function with age remain unclear. We examined the plasma proteomic profile associated with longitudinal changes in physical function measured by gait speed and grip strength in community-dwelling adults. We applied an aptamer-based platform to assay 1154 plasma proteins on 2854 participants (60% women, aged 76 years) in the Cardiovascular Health Study (CHS) in 1992-1993 and 1130 participants (55% women, aged 54 years) in the Framingham Offspring Study (FOS) in 1991-1995. Gait speed and grip strength were measured annually for 7 years in CHS and at cycles 7 (1998-2001) and 8 (2005-2008) in FOS. The associations of individual protein levels (log-transformed and standardized) with longitudinal changes in gait speed and grip strength in two populations were examined separately by linear mixed-effects models. Meta-analyses were implemented using random-effects models and corrected for multiple testing. We found that plasma levels of 14 and 18 proteins were associated with changes in gait speed and grip strength, respectively (corrected p < 0.05). The proteins most strongly associated with gait speed decline were GDF-15 (Meta-analytic p = 1.58 × 10-15 ), pleiotrophin (1.23 × 10-9 ), and TIMP-1 (5.97 × 10-8 ). For grip strength decline, the strongest associations were for carbonic anhydrase III (1.09 × 10-7 ), CDON (2.38 × 10-7 ), and SMOC1 (7.47 × 10-7 ). Several statistically significant proteins are involved in the inflammatory responses or antagonism of activin by follistatin pathway. These novel proteomic biomarkers and pathways should be further explored as future mechanisms and targets for age-related functional decline.

  View details for DOI 10.1111/acel.13736

  View details for PubMedID 36333824

• DECIPHERING RACIAL AND ETHNIC DISPARITIES IN DEMENTIA AND COGNITIVE FUNCTION: A POLYSOCIAL SCORE APPROACH Wu, C., Ping, Y., Chen, X., Odden, M., Prina, M. OXFORD UNIV PRESS. 2022: 1

  View details for Web of Science ID 000913044000003

• PLASMA PROTEOMIC SIGNATURE OF DECLINE IN GAIT SPEED AND GRIP STRENGTH Liu, X., Pan, S., Xanthakis, V., Ramachandran, V., Newman, A., Sanders, J., Austin, T., Odden, M. OXFORD UNIV PRESS. 2022: 215

  View details for Web of Science ID 000913044001070

• Prevalence of Apparent Treatment-Resistant Hypertension in Chronic Kidney Disease in Two Large US Health Care Systems CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY An, J., Kurella Tamura, M., Odden, M. C., Ni, L., Thomas, I., Montez-Rath, M. E., Sim, J. J. 2022; 17 (10): 1457-1466

  View details for DOI 10.2215/CJN.04110422

  View details for Web of Science ID 000863522000007

• RACIAL AND ETHNIC DISPARITIES IN YEARS OF POTENTIAL LIFE LOST ASSOCIATED WITH CIRRHOSIS IN THE UNITED STATES BEFORE AND DURING THE COVID-19 PANDEMIC Yeo, Y., Zhao, Y., Samaan, J., Lv, F., He, X., Liu, Y., Gao, N., Odden, M. C., Ji, F., Nguyen, M. H. WILEY. 2022: S1074-S1075

  View details for Web of Science ID 000870796603231

• THE TREND OF YEARS OF POTENTIAL LIFE LOST ASSOCIATED WITH CIRRHOSIS BEFORE AND DURING THE COVID-19 PANDEMIC: A POPULATION-BASED STUDY Zhao, Y., Yeo, Y., Samaan, J., Lv, F., He, X., Gao, N., Park, J., Yang, J., Ayoub, W. S., Odden, M. C., Ji, F., Nguyen, M. H. WILEY. 2022: S74-S75

  View details for Web of Science ID 000870796600084

• Prevalence of Apparent Treatment-Resistant Hypertension in Chronic Kidney Disease in Two Large US Health Care Systems. Clinical journal of the American Society of Nephrology : CJASN An, J., Kurella Tamura, M., Odden, M. C., Ni, L., Thomas, I. C., Montez-Rath, M. E., Sim, J. J. 2022; 17 (10): 1457-1466

  Abstract

  More intensive BP goals have been recommended for patients with CKD. We estimated the prevalence of apparent treatment-resistant hypertension among patients with CKD according to the 2017 American College of Cardiology/American Heart Association (ACC/AHA; BP goal <130/80 mm Hg) and 2021 Kidney Disease Improving Global Outcomes (KDIGO; systolic BP <120 mm Hg) guidelines in two US health care systems.We included adults with CKD (an eGFR <60 ml/min per 1.73 m2) and treated hypertension from Kaiser Permanente Southern California and the Veterans Health Administration. Using electronic health records, we identified apparent treatment-resistant hypertension on the basis of (1) BP above the goal while prescribed three or more classes of antihypertensive medications or (2) prescribed four or more classes of antihypertensive medications regardless of BP. In a sensitivity analysis, we required diuretic use to be classified as apparent treatment-resistant hypertension. We estimated the prevalence of apparent treatment-resistant hypertension per clinical guideline and by CKD stage.Among 44,543 Kaiser Permanente Southern California and 241,465 Veterans Health Administration patients with CKD and treated hypertension, the prevalence rates of apparent treatment-resistant hypertension were 39% (Kaiser Permanente Southern California) and 35% (Veterans Health Administration) per the 2017 ACC/AHA guideline and 48% (Kaiser Permanente Southern California) and 55% (Veterans Health Administration) per the 2021 KDIGO guideline. By requiring a diuretic as a criterion for apparent treatment-resistant hypertension, the prevalence rates of apparent treatment-resistant hypertension were lowered to 31% (Kaiser Permanente Southern California) and 23% (Veterans Health Administration) per the 2017 ACC/AHA guideline. The prevalence rates of apparent treatment-resistant hypertension were progressively higher at more advanced stages of CKD (34%/33%, 42%/36%, 52%/41%, and 60%/37% for Kaiser Permanente Southern California/Veterans Health Administration eGFR 45-59, 30-44, 15-29, and <15 ml/min per 1.73 m2, respectively) per the 2017 ACC/AHA guideline.Depending on the CKD stage, up to a half of patients with CKD met apparent treatment-resistant hypertension criteria.

  View details for DOI 10.2215/CJN.04110422

  View details for PubMedID 36400564

• Most excess years of potential life loss among individuals with cirrhosis during the pandemic were not related to COVID-19. Gut Zhao, Y., Yeo, Y. H., Samaan, J., Lv, F., He, X., Gao, N., Park, J., Yang, J. D., Ayoub, W., Odden, M. C., Ji, F., Nguyen, M. H. 2022

  View details for DOI 10.1136/gutjnl-2022-328188

  View details for PubMedID 36282906

• Most excess years of potential life loss among individuals with cirrhosis during the pandemic were not related to COVID-19 GUT Zhao, Y., Yeo, Y., Samaan, J., Lv, F., He, X., Gao, N., Park, J., Yang, J., Ayoub, W., Odden, M. C., Ji, F., Nguyen, M. H. 2022

  View details for DOI 10.1136/gutjnl-2022-328188

  View details for Web of Science ID 000850850100001

• Tobacco smoking, intensity, and duration are associated with frailty among people with HIV Ruderman, S., Crane, H., Webel, A., Fitzpatrick, A., Odden, M., Crane, P., Willig, A., Nance, R., Drumright, L., Whitney, B., Ma, J., Haidar, L., Mayer, K., Eron, J., Christopoulos, K., Greene, M., Mathews, W., Saag, M., Kamen, C., Hahn, A., Kitahata, M., Delaney, J. WILEY. 2022: 13-14

  View details for Web of Science ID 000859084400023

• Intensive Versus Standard Blood Pressure Lowering and Days Free of Cardiovascular Events and Serious Adverse Events: a Post Hoc Analysis of Systolic Blood Pressure Intervention Trial. Journal of general internal medicine Kim, D. H., Tatsuoka, C., Chen, Z., Wright, J. T., Odden, M. C., Beddhu, S., Bellows, B. K., Bress, A., Carson, T., Cushman, W. C., Johnson, K. C., Morisky, D. E., Punzi, H., Tamariz, L., Yang, S., Wei, L. 2022

  Abstract

  BACKGROUND: Communication of the benefits and harms of blood pressure lowering strategy is crucial for shared decision-making.OBJECTIVES: To quantify the effect of intensive versus standard systolic blood pressure lowering in terms of the number of event-free days DESIGN: Post hoc analysis of the Systolic Blood Pressure Intervention Trial PARTICIPANTS: A total of 9361 adults 50 years or older without diabetes or stroke who had a systolic blood pressure of 130-180 mmHg and elevated cardiovascular risk INTERVENTIONS: Intensive (systolic blood pressure goal <120 mmHg) versus standard blood pressure lowering (<140 mmHg) MAIN MEASURES: Days free of major adverse cardiovascular events (MACE), serious adverse events (SAE), and monitored adverse events (hypotension, syncope, bradycardia, electrolyte abnormalities, injurious falls, or acute kidney injury) over a median follow-up of 3.33 years KEY RESULTS: The intensive treatment group gained 14.7 more MACE-free days over 4 years (difference, 14.7 [95% confidence interval: 5.1, 24.4] days) than the standard treatment group. The benefit of the intensive treatment varied by cognitive function (normal: difference, 40.7 [13.0, 68.4] days; moderate-to-severe impairment: difference, -15.0 [-56.5, 26.4] days; p-for-interaction=0.009) and self-rated health (excellent: difference, -22.7 [-51.5, 6.1] days; poor: difference, 156.1 [31.1, 281.2] days; p-for-interaction=0.001). The mean overall SAE-free days were not significantly different between the treatments (difference, -14.8 [-35.3, 5.7] days). However, the intensive treatment group had 28.5 fewer monitored adverse event-free days than the standard treatment group (difference, -28.5 [-40.3, -16.7] days), with significant variations by frailty status (non-frail: difference, 38.8 [8.4, 69.2] days; frail: difference, -15.5 [-46.6, 15.7] days) and self-rated health (excellent: difference, -12.9 [-45.5, 19.7] days; poor: difference, 180.6 [72.9, 288.4] days; p-for-interaction <0.001).CONCLUSIONS: Over 4 years, intensive systolic blood pressure lowering provides, on average, 14.7 more MACE-free days than standard treatment, without any difference in SAE-free days. Whether this time-based effect summary improves shared decision-making remains to be elucidated.TRIAL REGISTRATION: ClinicalTrials.gov Registration: NCT01206062.

  View details for DOI 10.1007/s11606-022-07753-5

  View details for PubMedID 35945470

• The association of hearing problems with social network strength and depressive symptoms: the cardiovascular health study. Age and ageing Dobrota, S. D., Biggs, M. L., Pratt, S., Popat, R., Odden, M. C. 2022; 51 (8)

  Abstract

  BACKGROUND: research on the association between hearing impairment and psychosocial outcomes is not only limited but also yielded mixed results.METHODS: we investigated associations between annual self-reports of hearing problems, depressive symptoms and social network strength among 5,888 adults from the Cardiovascular Health Study over a period of 9 years. Social network strength and depressive symptoms were defined using the Lubben Social Network Scale (LSNS), and the Center for Epidemiological Studies Depression Scale (CES-D).RESULTS: hearing problems were associated with weaker social networks and more depressive symptoms. These association differed for prevalent versus incident hearing problems. Participants with prevalent hearing problems scored an adjusted 0.47 points lower (95% CI: -2.20, -0.71) on the LSNS and 0.71 points higher (95% CI: 0.23, 1.19) on the CES-D than those without hearing problems. Participants with incident hearing problems had a greater decline of 0.12 points (95% CI: -0.12, -0.03) per year in social network score than individuals with no hearing problems after adjusting for confounders. Females appeared to be more vulnerable to changes in social network strength than males (P-value for interaction=0.02), but not for changes in depressive score. Accounting for social network score did not appear to attenuate the association between hearing problems and depressive score.CONCLUSION: findings suggest that older adults with prevalent hearing problems may be more at risk for depression, but individuals with incident hearing problems may be at greater risk for a winnowing of their social network.

  View details for DOI 10.1093/ageing/afac181

  View details for PubMedID 35977151

• Proteomics and Population Biology in the Cardiovascular Health Study (CHS): design of a study with mentored access and active data sharing. European journal of epidemiology Austin, T. R., McHugh, C. P., Brody, J. A., Bis, J. C., Sitlani, C. M., Bartz, T. M., Biggs, M. L., Bansal, N., Buzkova, P., Carr, S. A., deFilippi, C. R., Elkind, M. S., Fink, H. A., Floyd, J. S., Fohner, A. E., Gerszten, R. E., Heckbert, S. R., Katz, D. H., Kizer, J. R., Lemaitre, R. N., Longstreth, W. T., McKnight, B., Mei, H., Mukamal, K. J., Newman, A. B., Ngo, D., Odden, M. C., Vasan, R. S., Shojaie, A., Simon, N., Smith, G. D., Davies, N. M., Siscovick, D. S., Sotoodehnia, N., Tracy, R. P., Wiggins, K. L., Zheng, J., Psaty, B. M. 2022

  Abstract

  BACKGROUND: In the last decade, genomic studies have identified and replicated thousands of genetic associations with measures of health and disease and contributed to the understanding of the etiology of a variety of health conditions. Proteins are key biomarkers in clinical medicine and often drug-therapy targets. Like genomics, proteomics can advance our understanding of biology.METHODS AND RESULTS: In the setting of the Cardiovascular Health Study (CHS), a cohort study of older adults, an aptamer-based method that has high sensitivity for low-abundance proteins was used to assay 4979 proteins in frozen, stored plasma from 3188 participants (61% women, mean age 74years). CHS provides active support, including central analysis, for seven phenotype-specific working groups (WGs). Each CHS WG is led by one or two senior investigators and includes 10 to 20 early or mid-career scientists. In this setting of mentored access, the proteomic data and analytic methods are widely shared with the WGs and investigators so that they may evaluate associations between baseline levels of circulating proteins and the incidence of a variety of health outcomes in prospective cohort analyses. We describe the design of CHS, the CHS Proteomics Study, characteristics of participants, quality control measures, and structural characteristics of the data provided to CHS WGs. We additionally highlight plans for validation and replication of novel proteomic associations.CONCLUSION: The CHS Proteomics Study offers an opportunity for collaborative data sharing to improve our understanding of the etiology of a variety of health conditions in older adults.

  View details for DOI 10.1007/s10654-022-00888-z

  View details for PubMedID 35790642

• Associations of modifiable behavioral risk factor combinations at 65-74 years old with cognitive healthspan over 20 years. Psychosomatic medicine Smagula, S. F., Biggs, M. L., Jacob, M. E., Rawlings, A. M., Odden, M. C., Arnold, A., Newman, A. B., Buysse, D. J. 2022

  Abstract

  OBJECTIVE: Behavioral risk factors for dementia tend to co-occur and inter-relate, especially poor diet, physical inactivity, sleep disturbances, and depression. Having multiple of these modifiable behavioral risk factors (MBRFs) may predict a particularly shortened cognitive healthspan, and therefore, may signal high-risk status/high intervention need.METHODS: This secondary analyses of data from the Cardiovascular Health Study included 3149 participants aged 65-74 years (mean age = 69.5, standard deviation (SD) = 2.5; 59.6% female). MBRF exposures were self-reports regarding: (1) diet, (2) activity, (3) sleep, and (4) depression symptoms. We primarily analyzed MBRF counts. Over up to 26 years of follow-up, we assessed the: (1) number of remaining cognitively healthy life years (CHLYs); and (2) percentage of remaining life years (LYs) that were CHLYs (%CHLY). We estimated CHLYs as time before a dementia diagnosis, cognitive screener scores indicating impairment, proxy port indicating significant cognitive decline, or dementia medication use.RESULTS: Participants averaged a remaining 16 LYs (SD = 7), 12.2 CHLYs (SD = 6.6), and 78.1% of LYs being CHLYs (SD = 25.6). Compared with having no MBRFs, having one was associated with ~1 less LY and CHLY, but not a relatively lower %CHLY. In contrast, having 3+ MBRFs was associated with about 2-3 fewer LYs and CHLYs as well as about 6% lower %CHLY (95% confidence interval: -9.0, -2.5 %CHLYs), p = 0.001).CONCLUSIONS: MBRF-related reductions in the cognitive healthspan are most apparent when people have multiple MBRFs. Future research is needed to determine if/how behavioral risks converge mechanistically, and if dementia prevention efficacy improves when targeting MBRF combinations.

  View details for DOI 10.1097/PSY.0000000000001100

  View details for PubMedID 35796682

• Discrimination, Mediating Psychosocial or Economic Factors, and Antihypertensive Treatment: A 4-Way Decomposition Analysis in the Health and Retirement Study. American journal of epidemiology Sims, K. D., Batty, G. D., Smit, E., Hystad, P. W., McGregor, J. C., Odden, M. C. 2022

  Abstract

  Untested psychosocial or economic factors mediate associations between perceived discrimination and suboptimal antihypertensive therapy. This study included two waves of data from the Health and Retirement Study participants with self-reported hypertension (N=8557, 73% Non-Hispanic White, 17% Non-Hispanic Black, and 10% Hispanic/Latino) over four years (2008-2014). Our primary exposures were frequency of experiencing discrimination in everyday life or across seven lifetime circumstances. Candidate mediators were self-reported depressive symptoms, subjective social standing, and household wealth. We evaluated with causal mediation methods the interactive and mediating associations between each discrimination measure and reported antihypertensive use at the subsequent wave. In unmediated analyses, everyday (OR; 95% CI: 0.86; 0.78, 0.95) as well as lifetime discrimination (OR; 95% CI: 0.91; 0.85, 0.98) were associated with a lower likelihood of antihypertensive use. Discrimination was associated with lower wealth, greater depressive symptoms, and decreased subjective social standing. Estimates for associations due to neither interaction nor mediation resembled unmediated associations for most discrimination-mediator combinations. Lifetime discrimination was indirectly associated with reduced antihypertensive use via depressive symptomology (OR; 95% CI: 0.99; 0.98, 1.00). In conclusion, the impact of lifetime discrimination on the underuse of antihypertensive therapy appears partially mediated by depressive symptoms.

  View details for DOI 10.1093/aje/kwac102

  View details for PubMedID 35689640

• Trends in blood pressure diagnosis, treatment, and control among VA nursing home residents, 2007-2018. Journal of the American Geriatrics Society Odden, M. C., Li, Y., Graham, L. A., Steinman, M. A., Marcum, Z. A., Liu, C. K., Jing, B., Fung, K. Z., Peralta, C. A., Lee, S. J. 2022

  Abstract

  BACKGROUND: Inadequate treatment of high blood pressure (BP) can lead to preventable adverse events in nursing home residents, while excessive treatment can lead to associated harms.METHODS: Data were extracted from the VA electronic health record and Bar Code Medication Administration system on 40,079 long-term care residents aged ≥65years from October 2006 through September 2018 (FY2007-2018). Hypertension prevalence at admission was identified by ICD code(s) in the year prior, and antihypertensive medication use was defined as administration ≥50% of days. BP measures were averaged over 2-year epochs.RESULTS: The age-standardized prevalence of hypertension diagnosis at admission increased from 75.2% in FY2007-2008 to 85.1% in FY2017-2018 (p-value for trend <0.001). Rates of BP treatment and control among residents with hypertension at admission declined slightly over time (p-values for trend <0.001) but remained high (80.3% treated in FY2017-2018, 80.1% with average BP <140/90mmHg). The age-adjusted prevalence of chronic low BP (average <90/60mmHg) also declined from 11.1% in FY2007-2008 to 4.7% in FY2017-2018 (p-value for trend <0.001). Persons identified as Black race or Hispanic ethnicity and those with a history of diabetes, stroke, and renal disease were less likely to have an average BP <140/90mmHg.CONCLUSIONS: Hypertension is well controlled in VA nursing homes, and recent trends of less intensive BP control were accompanied by a lower prevalence of chronic low BP. Nonetheless, some high-risk populations have average BP levels >140/90mmHg. Future research is needed to better understand the benefits and harms of BP control in nursing home residents.

  View details for DOI 10.1111/jgs.17821

  View details for PubMedID 35524763

• Association of Peripheral Lymphocyte Subsets with Cognitive Decline and Dementia: The Cardiovascular Health Study. Journal of Alzheimer's disease : JAD Fohner, A. E., Sitlani, C. M., Buzkova, P., Doyle, M. F., Liu, X., Bis, J. C., Fitzpatrick, A., Heckbert, S. R., Huber, S. A., Kuller, L., Longstreth, W. T., Feinstein, M. J., Freiberg, M., Olson, N. C., Seshadri, S., Lopez, O., Odden, M. C., Tracy, R. P., Psaty, B. M., Delaney, J. A., Floyd, J. S. 2022

  View details for DOI 10.3233/JAD-220091

  View details for PubMedID 35527553

• Statins and Cognitive Decline in the Cardiovascular Health Study: A Comparison of Different Analytical Approaches. The journals of gerontology. Series A, Biological sciences and medical sciences Zeki Al Hazzouri, A., Jawadekar, N., Grasset, L., Kaiser, P., Kezios, K., Calonico, S., Glymour, M., Hirsch, C., Arnold, A. M., Varadhan, R., Odden, M. C. 2022; 77 (5): 994-1001

  Abstract

  Despite their well-established benefits for the prevention of cardiovascular disease, robust evidence on the effects of statins on cognition is largely inconclusive. We apply various study designs and analytical approaches to mimic randomized controlled trial effects from observational data.We used observational data from 5 580 participants enrolled in the Cardiovascular Health Study from 1989/1990 to 1999/2000. We conceptualized the cohort as an overlapping sequence of nonrandomized trials. We compared multiple selection (eligible population, prevalent users, new users) and analytic approaches (multivariable adjustment, inverse-probability treatment weights, propensity score matching) to evaluate the association between statin use and 5-year change in global cognitive function, assessed using the Modified Mini-Mental State Examination (3MSE).When comparing prevalent users to nonusers (N = 2 772), statin use was associated with slower cognitive decline over 5 years (adjusted annual change in 3MSE = 0.34 points/year; 95% CI: 0.05-0.63). Compared to prevalent user design, estimates from new user designs (eg, comparing eligible statin initiators to noninitiators) were attenuated showing either null or negative association, though not significant. For example, in a propensity score-matched sample of statin-eligible individuals (N = 454), the annual 3MS change comparing statin initiators to noninitiators was -0.21 points/year (95% CI: -0.81 to 0.39).The association of statin use and cognitive decline is attenuated toward the null when using rigorous analytical approaches that more closely mimic randomized controlled trials. Point estimates, even within the same study, may vary depending on the analytical methods used. Further studies that leverage natural or quasi experiments around statin use are needed to replicate our findings.

  View details for DOI 10.1093/gerona/glab220

  View details for PubMedID 34331536

  View details for PubMedCentralID PMC9071443

• Aging Hearts in a Hotter, More Turbulent World: The Impacts of Climate Change on the Cardiovascular Health of Older Adults. Current cardiology reports Chang, A. Y., Tan, A. X., Nadeau, K. C., Odden, M. C. 2022

  Abstract

  PURPOSE OF REVIEW: Climate change has manifested itself in multiple environmental hazards to human health. Older adults and those living with cardiovascular diseases are particularly susceptible to poor outcomes due to unique social, economic, and physiologic vulnerabilities. This review aims to summarize those vulnerabilities and the resultant impacts of climate-mediated disasters on the heart health of the aging population.RECENT FINDINGS: Analyses incorporating a wide variety of environmental data sources have identified increases in cardiovascular risk factors, hospitalizations, and mortality from intensified air pollution, wildfires, heat waves, extreme weather events, rising sea levels, and pandemic disease. Older adults, especially those of low socioeconomic status or belonging to ethnic minority groups, bear a disproportionate health burden from these hazards. The worldwide trends responsible for global warming continue to worsen climate change-mediated natural disasters. As such, additional investigation will be necessary to develop personal and policy-level interventions to protect the cardiovascular wellbeing of our aging population.

  View details for DOI 10.1007/s11886-022-01693-6

  View details for PubMedID 35438387

• Corrigendum to: Quantifying and Classifying Physical Resilience Among Older Adults: The Health, Aging, and Body Composition Study. The journals of gerontology. Series A, Biological sciences and medical sciences Wu, C., Li, Y., Marron, M. M., Odden, M. C., Newman, A. B., Sanders, J. L. 2022

  View details for DOI 10.1093/gerona/glac048

  View details for PubMedID 35435959

• How Low Should You Go in the Presence of Frailty? Hypertension (Dallas, Tex. : 1979) Odden, M. C., Anderson, T. S. 2022; 79 (1): 33-35

  View details for DOI 10.1161/HYPERTENSIONAHA.121.18373

  View details for PubMedID 34878900

• Promoting Health Equity Across the Life Span. The journals of gerontology. Series A, Biological sciences and medical sciences Odden, M. C., Thorpe, R. J. 2022; 77 (2): 297-298

  View details for DOI 10.1093/gerona/glab359

  View details for PubMedID 35134863

• Adolescent individual, school, and neighborhood influences on young adult hypertension risk. PloS one Abdel Magid, H. S., Milliren, C. E., Rice, K., Molanphy, N., Ruiz, K., Gooding, H. C., Richmond, T. K., Odden, M. C., Nagata, J. M. 2022; 17 (4): e0266729

  Abstract

  BACKGROUND: Geographic and contextual socioeconomic risk factors in adolescence may be more strongly associated with young adult hypertension than individual-level risk factors. This study examines the association between individual, neighborhood, and school-level influences during adolescence on young adult blood pressure.METHODS: Data were analyzed from the National Longitudinal Study of Adolescent to Adult Health (1994-1995 aged 11-18 and 2007-2008 aged 24-32). We categorized hypertension as systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg. Secondary outcomes included continuous systolic and diastolic blood pressure. We fit a series of cross-classified multilevel models to estimate the associations between young adulthood hypertension with individual-level, school-level, and neighborhood-level factors during adolescence (i.e., fixed effects) and variance attributable to each level (i.e., random effects). Models were fit using Bayesian estimation procedures. For linear models, intra-class correlations (ICC) are reported for random effects.RESULTS: The final sample included 13,911 participants in 128 schools and 1,917 neighborhoods. Approximately 51% (7,111) young adults were hypertensive. Individual-level characteristics-particularly older ages, Non-Hispanic Black race, Asian race, male sex, BMI, and current smoking-were associated with increased hypertension. Non-Hispanic Black (OR = 1.21; 95% CI: 1.03-1.42) and Asian (OR = 1.28; 95% CI: 1.02-1.62) students had higher odds of hypertension compared to non-Hispanic White students. At the school level, hypertension was associated with the percentage of non-Hispanic White students (OR for 10% higher = 1.06; 95% CI: 1.01-1.09). Adjusting for individual, school, and neighborhood predictors attenuated the ICC for both the school (from 1.4 null to 0.9 fully-adjusted) and neighborhood (from 0.4 to 0.3).CONCLUSION: We find that adolescents' schools and individual-level factors influence young adult hypertension, more than neighborhoods. Unequal conditions in school environments for adolescents may increase the risk of hypertension later in life. Our findings merit further research to better understand the mechanisms through which adolescents' school environments contribute to adult hypertension and disparities in hypertension outcomes later in life.

  View details for DOI 10.1371/journal.pone.0266729

  View details for PubMedID 35482649

• Racial Residential Segregation in Young Adulthood and Brain Integrity in Middle Age: Can We Learn From Small Samples? American journal of epidemiology Al Hazzouri, A. Z., Jawadekar, N., Kezios, K., Caunca, M. R., Elfassy, T., Calonico, S., Kershaw, K. N., Yaffe, K., Launer, L., Elbejjani, M., Grasset, L., Manly, J., Odden, M. C., Glymour, M. M. 2022

  Abstract

  Racial residential segregation is associated with multiple adverse health outcomes in Black individuals. Yet, the influence of structural racism and racial residential segregation on brain aging is less understood. In this study, we investigate the association between cumulative exposure to racial residential segregation over 25 years (1985-2010) of young adulthood, measured by the Getis-Ord Gi*-statistic, and year 25 measures of brain volume in midlife (cerebral, gray matter, white matter, and hippocampal volumes). We studied 290 Black participants with available brain imaging data who were enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) prospective cohort study. CARDIA originally recruited 2637 Black participants aged 18 to 30 years old from 4 field centers across the United States. We conducted analyses using marginal structural models, incorporating inverse probability weighting and inverse censoring weighting. We found that compared to low/medium segregation, greater cumulative exposure to residential segregation throughout young adulthood was associated with smaller brain volumes in general (e.g. β for cerebral volume: -0.08 [95% CI]: [-0.15, -0.02]) and with a more pronounced reduction in hippocampal volume, though results were not statistically significant. Our findings suggest that exposure to segregated neighborhoods may be associated with worse brain aging.

  View details for DOI 10.1093/aje/kwab297

  View details for PubMedID 35020781

• Statin Use and Reduced Hepatocellular Carcinoma Risk in Patients with Non-alcoholic Fatty Liver Disease. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Zou, B., Odden, M. C., Nguyen, M. H. 2022

  Abstract

  Recent evidence suggests potential clinical benefits of statin in cancer chemoprevention and treatment. Non-alcoholic fatty liver disease (NAFLD) is expected to become the leading cause of hepatocellular carcinoma (HCC). We aimed to investigate the association between statin initiation and the risk of HCC among patients with NAFLD.In this study using the Optum de-identified Clinformatics® database, cox proportional-hazards regression model was performed to determine the risk of HCC in statin initiators versus nonusers. We incorporated inverse probability of treatment weighting (IPTW) to minimize potential confounding.Among 272,431 adults with NAFLD diagnosis, IPTW model shows that statin initiators had a 53% less risk of developing HCC compared to nonusers (HR: 0.47, 95% confidence interval: 0.36-0.60). In the sub-cohort with FIB-4 data available, statin initiation was associated with a 56% hazard reduction of developing HCC in NAFLD after adjusting for FIB-4 score (HR: 0.44; 0.30-0.65). The association between statin initiation and lower risk of HCC development was observed for both lipophilic statin (HR: 0.49; 0.37-0.65) and hydrophilic statin (HR: 0.40; 0.21-0.76). Moreover, we observed a greater hazards reduction as the dose and duration of statin use increased. NAFLD patients with more than 600 cDDDs of statin had a 70% reduction in hazards of developing HCC (HR: 0.30; 0.20-0.43).Our study provides strong evidence for the association between statin initiation and reduced risk of HCC development in NAFLD patients. These findings imply that statin can be used as a protective medication for NAFLD patients to reduce the risk of HCC.

  View details for DOI 10.1016/j.cgh.2022.01.057

  View details for PubMedID 35158055

• Association of Antihypertensives and Cognitive Impairment in Long-Term Care Residents. Journal of Alzheimer's disease : JAD Marcum, Z. A., Li, Y., Lee, S. J., Steinman, M. A., Graham, L., Jing, B., Fung, K., Peralta, C. A., Odden, M. C. 2022

  Abstract

  Certain classes of antihypertensive medication may have different associations with cognitive impairment.To examine the association between prevalent use of antihypertensive medications that stimulate (thiazides, dihydropyridine calcium channel blockers, angiotensin type I receptor blockers) versus inhibit (angiotensin-converting enzyme inhibitors, beta-blockers, non-dihydropyridine calcium channel blockers) type 2 and 4 angiotensin II receptors on cognitive impairment among older adults residing in Veterans Affairs (VA) nursing homes for long-term care.Retrospective cohort study. Long-term care residents aged 65 + years admitted to a VA nursing home from 2012 to 2019 using blood pressure medication and without cognitive impairment at admission. Main exposure was prevalent use of angiotensin II receptor type 2 and 4-'stimulating' (N = 589), 'inhibiting' (N = 3,219), or 'mixed' (N = 1,715) antihypertensive medication regimens at admission. Primary outcome was any cognitive impairment (Cognitive Function Scale).Over an average of 5.4 months of follow-up, prevalent use of regimens containing exclusively 'stimulating' antihypertensives was associated with a lower risk of any incident cognitive impairment as compared to prevalent use of regimens containing exclusively 'inhibiting' antihypertensives (HR 0.83, 95% CI 0.74-0.93). Results for the comparison between 'mixed' versus 'inhibiting' regimens were in the same direction but not statistically significant (HR 0.96, 95% CI 0.88-1.06).For residents without cognitive impairment at baseline, prevalent users of regimens containing exclusively antihypertensives that stimulate type 2 and 4 angiotensin II receptors had lower rates of cognitive impairment as compared to prevalent users of regimens containing exclusively antihypertensives that inhibit these receptors. Residual confounding cannot be ruled out.

  View details for DOI 10.3233/JAD-215393

  View details for PubMedID 35147539

• A Call to Action to Enhance Justice, Equity, Diversity, and Inclusion in the Journal of Gerontology Series A: Medical Sciences. The journals of gerontology. Series A, Biological sciences and medical sciences Thorpe, R. J., Odden, M. C., Lipsitz, L. A. 2021

  View details for DOI 10.1093/gerona/glab284

  View details for PubMedID 34791249

• REDUCED HEPATOCELLULAR CARCINOMA RISK IN STATIN USERS WITH NON-ALCOHOLIC FATTY LIVER DISEASE: A NATIONWIDE US STUDY Zou, B., Odden, M. C., Nguyen, M. H. WILEY. 2021: 666A

  View details for Web of Science ID 000707188003167

• Exploring the Dynamics of Week-to-Week Blood Pressure in Nursing Home Residents Before Death. American journal of hypertension Graham, L. A., Lee, S. J., Steinman, M., Peralta, C. A., Rubinsky, A., Jing, B., Fung, K., Odden, M. C. 2021

  Abstract

  BACKGROUND: Aging is accompanied by an overall dysregulation of many dynamic physiologic processes including those related to blood pressure (BP). While year-to-year BP variability is associated with cardiovascular events and mortality, no studies have examined this trend with more frequent BP assessments. Our study objective is to take the next step to examine week-to-week BP dynamics - pattern, variability, and complexity - before death.METHODS: Using a retrospective study design, we assessed BP dynamics in the 6 months before death in long-term nursing home residents between 10/1/2006 and 9/30/2017. Variability was characterized using standard deviation and mean square error after adjusting for diurnal variations. Complexity (i.e., amount of novel information in a trend) was examined using Shannon's entropy (bits). Generalized linear models were used to examine factors associated with overall BP variability.RESULTS: We identified 17,953 nursing home residents (98.0% male, 82.5% White, mean age 80.2 years, and mean BP 125.7/68.6 mmHg). Despite a slight trend of decreasing systolic week-to-week BP over time (delta=7.2mmHg), week-to-week complexity did not change in the six months before death (delta=0.02 bits). Average weekly BP variability was stable until the last 3-4 weeks of life, at which point variability increased by 30% for both systolic and diastolic BP. Factors associated with BP variability include average weekly systolic/diastolic BP, days in the nursing home, days in the hospital, and changes to antihypertensive medications.CONCLUSIONS: Week-to-week BP variability increases substantially in the last month of life, but complexity does not change. Changes in care patterns may drive the increase in BP variability as one approaches death.

  View details for DOI 10.1093/ajh/hpab142

  View details for PubMedID 34505872

• Creation and validation of a polysocial score for mortality among community-dwelling older adults in the USA: the health and retirement study. Age and ageing Ping, Y., Odden, M. C., Stawski, R. S., Abdel Magid, H. S., Wu, C. 2021

  Abstract

  BACKGROUND: the interrelatedness between social determinants of health impedes researchers to identify important social factors for health investment. A new approach is needed to quantify the aggregate effect of social factors and develop person- centred social interventions.METHODS: participants ([n=7,383], 54.5% female) were aged 65years or above who complete an additional psychosocial questionnaire in the health and retirement study in 2006 or 2008. Social determinants of health encompassed five social domains: economic stability, neighbourhood and physical environment, education, community and social context, and healthcare system. We used the forward stepwise logistic regression to derive a polysocial score model for 5-year mortality. Indices of goodness-of-fit, discrimination and reclassification were used to assess model performance. We used logistic regression to identify the association between polysocial score and mortality. Subgroup analyses were conducted to examine sex- and race-specific association.RESULTS: polysocial score was created using 14 social determinants of health. In the training cohort, the C-statistic was 0.71 for the reference model (only age, sex and race/ethnicity) and increased to 0.75 for the continuous and categorical polysocial score. Compared with the reference model, the integrated discrimination index for adding the continuous or categorical polysocial score was both 0.03 (P values < 0.001). Participants with an intermediate (odds ratio [OR]=0.69; 95% confidence interval [CI], 0.51-0.82) or high (OR=0.48; 95% CI, 0.38-0.60) polysocial score had lower odds of death than those in the low category in the fully adjusted model, respectively.CONCLUSIONS: the polysocial approach may offer possible solutions to monitor social environments and suggestions for older people to improve their social status for specific health outcomes.

  View details for DOI 10.1093/ageing/afab174

  View details for PubMedID 34473824

• Intersectional Discrimination and Change in Blood Pressure Control among Older Adults: The Health and Retirement Study. The journals of gerontology. Series A, Biological sciences and medical sciences Sims, K. D., Smit, E., Batty, G. D., Hystad, P. W., Odden, M. C. 2021

  Abstract

  BACKGROUND: Associations between multiple forms of discrimination and blood pressure control in older populations remain unestablished.METHODS: Participants were 14582 non-institutionalized individuals (59% women) in the Health and Retirement Study aged at least 51 years (76% Non-Hispanic White, 15% Non-Hispanic Black, 9% Hispanic/Latino). Primary exposures included the mean frequency of discrimination in everyday life, intersectional discrimination (defined as marginalization ascribed to more than one reason), and the sum of discrimination over the lifespan. We assessed whether discrimination was associated with change in measured hypertension status (N=14582) and concurrent medication use among reported hypertensives (N=9086) over four years (2008-2014).RESULTS: There was no association between the frequency of everyday discrimination and change in measured hypertension. Lifetime discrimination was associated with higher odds of hypertension four years later among men (OR: 1.21, 95% CI: 1.08, 1.36) but not women (OR: 0.98, 95% CI: 0.86, 1.13). Only among men, everyday discrimination due at least two reasons was associated with a 1.44 (95% CI: 1.03, 2.01)-fold odds of hypertension than reporting no everyday discrimination; reporting intersectional discrimination was not associated with developing hypertension among women (OR: 0.91, 95% CI: 0.70, 1.20). All three discriminatory measures were inversely related to time-averaged antihypertensive medication use, without apparent gender differences (e.g., OR for everyday discrimination-antihypertensive use associations: 0.85, 95% CI: 0.77, 0.94)).CONCLUSIONS: Gender differences in marginalization may more acutely elevate hypertensive risk among older men than similarly aged women. Experiences of discrimination appear to decrease the likelihood of antihypertensive medication use among older adults overall.

  View details for DOI 10.1093/gerona/glab234

  View details for PubMedID 34390331

• Deprescribing Blood Pressure Treatment in Long-Term Care Residents. Journal of the American Medical Directors Association Odden, M. C., Lee, S. J., Steinman, M. A., Rubinsky, A. D., Graham, L., Jing, B., Fung, K., Marcum, Z., Peralta, C. A. 2021

  Abstract

  OBJECTIVES: To evaluate the incidence of deprescribing of antihypertensive medication among older adults residing in Veterans Affairs (VA) nursing homes for long-term care and rates of deprescribing after potentially triggering events.DESIGN: Retrospective cohort study.SETTING AND PARTICIPANTS: Long-term care residents aged 65years and older admitted to a VA nursing home from 2006 to 2019 and using blood pressure medication at admission.METHODS: Data were extracted from the VA electronic health record, and Centers for Medicare & Medicaid Services Minimum Data Set and Bar Code Medication Administration. Deprescribing was defined on a rolling basis as a reduction in the number or dose of antihypertensive medications, sustained for ≥2weeks. We examined potentially triggering events for deprescribing, including low blood pressure (<90/60mmHg), acute renal impairment (creatinine increase of 50%), electrolyte imbalance (potassium below 3.5 mEq/L, sodium decrease by 5 mEq/L), and falls.RESULTS: Among 31,499 VA nursing home residents on antihypertensive medication, 70.4% had ≥1 deprescribing event (median length of stay= 6months), and 48.7% had a net reduction in antihypertensive medications over their stay. Deprescribing events were most common in the first 4weeks after admission and the last 4weeks of life. Among potentially triggering events, a 50% increase in serum creatinine was associated with the greatest increase in the likelihood of deprescribing over the subsequent 4weeks: residents with this event had a 41.7% chance of being deprescribed compared with 11.5% in those who did not (risk difference= 30.3%, P < .001). A fall in the past 30days was associated with the smallest magnitude increased risk of deprescribing (risk difference= 3.8%, P < .001) of the events considered.CONCLUSIONS AND IMPLICATIONS: Deprescribing of antihypertensive medications is common among VA nursing home residents, especially after a potential renal adverse event.

  View details for DOI 10.1016/j.jamda.2021.07.009

  View details for PubMedID 34364847

• Cardiovascular Damage Phenotypes and All-Cause and CVD Mortality in Older Adults. Annals of epidemiology Miller, L. M., Wu, C., Hirsch, C. H., Lopez, O. L., Cushman, M., Odden, M. C. 2021

  Abstract

  PURPOSE: The association between CVD risk factors and mortality is well established, however, current tools for addressing subgroups have focused on the overall burden of disease. The identification of risky combinations of characteristics may lead to a better understanding of physiologic pathways that underlie morbidity and mortality in older adults.METHODS: Participants included 5,067 older adults from the Cardiovascular Health Study, followed for up to 6 years. Using latent class analysis (LCA), we created CV damage phenotypes based on probabilities of abnormal brain infarctions, major echocardiogram abnormalities, N-terminal pro-brain natriuretic peptide, troponin T, interleukin-6, c reactive-protein, galectin-3, cystatin C. We assigned class descriptions based on the probability of having an abnormality among risk factors, such that a healthy phenotype would have low probabilities in all risk factors. Participants were assigned to phenotypes based on the maximum probability of membership. We used Cox-proportional hazards regression to evaluate the association between the categorical CV damage phenotype and all-cause and CVD-mortality.RESULTS: The analysis yielded 5 CV damage phenotypes consistent with the following descriptions: healthy (59%), cardio-renal (11%), cardiac (15%), multisystem morbidity (6%), and inflammatory (9%). All four phenotypes were statistically associated with a greater risk of all-cause mortality when compared with the healthy phenotype. The multisystem morbidity phenotype had the greatest risk of all-cause death (HR: 4.02; 95% CI: 3.44, 4.70), and CVD-mortality (HR: 4.90, 95% CI: 3.95, 6.06).CONCLUSION: Five CV damage phenotypes emerged from CVD risk factor measures. CV damage across multiple systems confers a greater mortality risk compared to damage in any single domain.

  View details for DOI 10.1016/j.annepidem.2021.07.012

  View details for PubMedID 34339835

• Association Between Income Inequality and County-Level COVID-19 Cases and Deaths in the US. JAMA network open Tan, A. X., Hinman, J. A., Abdel Magid, H. S., Nelson, L. M., Odden, M. C. 2021; 4 (5): e218799

  Abstract

  Importance: Socioeconomically marginalized communities have been disproportionately affected by the COVID-19 pandemic. Income inequality may be a risk factor for SARS-CoV-2 infection and death from COVID-19.Objective: To evaluate the association between county-level income inequality and COVID-19 cases and deaths from March 2020 through February 2021 in bimonthly time epochs.Design, Setting, and Participants: This ecological cohort study used longitudinal data on county-level COVID-19 cases and deaths from March 1, 2020, through February 28, 2021, in 3220 counties from all 50 states, Puerto Rico, and the District of Columbia.Main Outcomes and Measures: County-level daily COVID-19 case and death data from March 1, 2020, through February 28, 2021, were extracted from the COVID-19 Data Repository by the Center for Systems Science and Engineering at Johns Hopkins University in Baltimore, Maryland.Exposure: The Gini coefficient, a measure of unequal income distribution (presented as a value between 0 and 1, where 0 represents a perfectly equal geographical region where all income is equally shared and 1 represents a perfectly unequal society where all income is earned by 1 individual), and other county-level data were obtained primarily from the 2014 to 2018 American Community Survey 5-year estimates. Covariates included median proportions of poverty, age, race/ethnicity, crowding given by occupancy per room, urbanicity and rurality, educational level, number of physicians per 100 000 individuals, state, and mask use at the county level.Results: As of February 28, 2021, on average, each county recorded a median of 8891 cases of COVID-19 per 100 000 individuals (interquartile range, 6935-10 666 cases per 100 000 individuals) and 156 deaths per 100 000 individuals (interquartile range, 94-228 deaths per 100 000 individuals). The median county-level Gini coefficient was 0.44 (interquartile range, 0.42-0.47). There was a positive correlation between Gini coefficients and county-level COVID-19 cases (Spearman rho=0.052; P<.001) and deaths (Spearman rho=0.134; P<.001) during the study period. This association varied over time; each 0.05-unit increase in Gini coefficient was associated with an adjusted relative risk of COVID-19 deaths: 1.25 (95% CI, 1.17-1.33) in March and April 2020, 1.20 (95% CI, 1.13-1.28) in May and June 2020, 1.46 (95% CI, 1.37-1.55) in July and August 2020, 1.04 (95% CI, 0.98-1.10) in September and October 2020, 0.76 (95% CI, 0.72-0.81) in November and December 2020, and 1.02 (95% CI, 0.96-1.07) in January and February 2021 (P<.001 for interaction). The adjusted association of the Gini coefficient with COVID-19 cases also reached a peak in July and August 2020 (relative risk, 1.28 [95% CI, 1.22-1.33]).Conclusions and Relevance: This study suggests that income inequality within US counties was associated with more cases and deaths due to COVID-19 in the summer months of 2020. The COVID-19 pandemic has highlighted the vast disparities that exist in health outcomes owing to income inequality in the US. Targeted interventions should be focused on areas of income inequality to both flatten the curve and lessen the burden of inequality.

  View details for DOI 10.1001/jamanetworkopen.2021.8799

  View details for PubMedID 33938935

• Association Between Myocardial Strain and Frailty in CHS. Circulation. Cardiovascular imaging Tan, A. X., Shah, S. J., Sanders, J. L., Psaty, B. M., Wu, C., Gardin, J. M., Peralta, C. A., Newman, A. B., Odden, M. C. 2021; 14 (5): e012116

  Abstract

  BACKGROUND: Myocardial strain, measured by speckle-tracking echocardiography, is a novel measure of subclinical cardiovascular disease and may reflect myocardial aging. We evaluated the association between myocardial strain and frailty-a clinical syndrome of lack of physiological reserve.METHODS: Frailty was defined in participants of the CHS (Cardiovascular Health Study) as having ≥3 of the following clinical criteria: weakness, slowness, weight loss, exhaustion, and inactivity. Using speckle-tracking echocardiography data, we examined the cross-sectional (n=3206) and longitudinal (n=1431) associations with frailty among participants who had at least 1 measure of myocardial strain, left ventricular longitudinal strain (LVLS), left ventricular early diastolic strain rate and left atrial reservoir strain, and no history of cardiovascular disease or heart failure at the time of echocardiography.RESULTS: In cross-sectional analyses, lower (worse) LVLS was associated with prevalent frailty; this association was robust to adjustment for left ventricular ejection fraction (adjusted odds ratio, 1.32 [95% CI, 1.07-1.61] per 1-SD lower strain; P=0.007) and left ventricular stroke volume (adjusted OR, 1.32 [95% CI, 1.08-1.61] per 1-SD lower strain; P=0.007). In longitudinal analyses, adjusted associations of LVLS and left ventricular early diastolic strain with incident frailty were 1.35 ([95% CI, 0.96-1.89] P=0.086) and 1.58 ([95% CI, 1.11-2.27] P=0.013, respectively). Participants who were frail and had the worst LVLS had a 2.2-fold increased risk of death (hazard ratio, 2.20 [95% CI, 1.81-2.66]; P<0.0001).CONCLUSIONS: In community-dwelling older adults without prevalent cardiovascular disease, worse LVLS by speckle-tracking echocardiography, reflective of subclinical myocardial dysfunction, was associated with frailty. Frailty and LVLS have an additive effect on mortality risk.

  View details for DOI 10.1161/CIRCIMAGING.120.012116

  View details for PubMedID 33993730

• Associations between 20-year lipid variability throughout young adulthood and midlife cognitive function and brain integrity. The journals of gerontology. Series A, Biological sciences and medical sciences Zeki Al Hazzouri, A., Caunca, M. R., Jawadekar, N., Grasset, L., Elfassy, T., Odden, M. C., Wu, C., Elbejjani, M., Launer, L., Yaffe, K. 2021

  Abstract

  BACKGROUND: Little is known about long-term lipid variability in young adulthood in relation to cognitive function and brain integrity in midlife.METHODS: We studied 3,328 adults from the Coronary Artery Risk Development in Young Adults. We defined low- and high- density lipoprotein (LDL, HDL) variability as the intra-individual standard deviation of lipid measurements over 20 years of young adulthood (1985-2005). Cognitive tests were administered in 2010. Brain scans were performed in 2010 on 714 participants. To facilitate comparison, cognitive tests and brain metrics were z-scored.RESULTS: Mean age at baseline was 25.4 years. Higher 20-year LDL variability was associated with worse verbal memory in midlife (beta=-0.25, 95% CI [-0.42, -0.08]), adjusted for important covariates. Higher 20-year HDL variability was associated with worse processing speed in midlife (beta=-0.80, 95% CI [-1.18, -0.41]) and brain integrity, e.g. smaller total brain volume (beta=-0.58, 95% CI [-0.82, -0.34]) and worse total brain fractional anisotropy (beta=-1.13, 95% CI [-1.87, -0.39]).CONCLUSIONS: Higher long-term lipid variability in adulthood was associated with worse cognition and brain integrity in midlife, in a relatively young cohort.

  View details for DOI 10.1093/gerona/glab108

  View details for PubMedID 33839774

• Characteristics of Populations Excluded From Clinical Trials Supporting Intensive Blood Pressure Control Guidelines. Journal of the American Heart Association Anderson, T. S., Odden, M. C., Penko, J., Kazi, D. S., Bellows, B. K., Bibbins-Domingo, K. 2021: e019707

  Abstract

  Background Only one third of patients recommended intensified treatment by the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline for high blood pressure would have been eligible for the clinical trials on which recommendations were largely based. We sought to identify characteristics of adults who would have been trial-ineligible in order to inform clinical practice and research priorities. Methods and Results We examined the proportion of adults diagnosed with hypertension who met trial inclusion and exclusion criteria, stratified by age, diabetes mellitus status, and guideline recommendations in a cross-sectional study of the National Health and Nutrition Examination Survey, 2013-2016. Of the 107.7million adults (95% CI, 99.3-116.0million) classified as having hypertension by the ACC/AHA guideline, 23.1% (95% CI, 20.8%-25.5%) were below the target blood pressure of 130/80mmHg, 22.2% (95% CI, 20.1%-24.4%) would be recommended nonpharmacologic treatment, and 54.6% (95% CI, 52.5%-56.7%) would be recommended additional pharmacotherapy. Only 20.6% (95% CI, 18.8%-22.4%) of adults with hypertension would be trial-eligible. The majority of adults <50 years were excluded because of low cardiovascular risk and lack of access to primary care. The majority of adults aged ≥70 years were excluded because of multimorbidity and limited life expectancy. Reasons for trial exclusion were similar for patients with and without diabetes mellitus. Conclusions Intensive blood pressure treatment trials were not representative of many younger adults with low cardiovascular risk and older adults with multimorbidity who are now recommended more intensive blood pressure goals.

  View details for DOI 10.1161/JAHA.120.019707

  View details for PubMedID 33754796

• Balance and cognitive decline in older adults in the cardiovascular health study. Age and ageing Meunier, C. C., Smit, E., Fitzpatrick, A. L., Odden, M. C. 2021

  Abstract

  BACKGROUND: Previous studies have demonstrated an association between gait speed and cognitive function. However, the relationship between balance and cognition remains less well explored. This study examined the cross-sectional and longitudinal relationship of balance and cognitive decline in older adults.METHODS: A cohort of 4,811 adults, aged ≥65years, participating in the Cardiovascular Health Study was followed for 6years. Modified Mini-Mental State Examination (3MSE) and Digit Symbol Substitution Test (DSST) were used to measure cognition. Tandem balance measures were used to evaluate balance. Regression models were adjusted for demographics, behavioural and disease factors.RESULTS: Worse balance was independently associated with worse cognition in cross-sectional analysis. Longitudinally, participants aged ≥76years with poorer balance had a faster rate of decline after adjustment for co-variates: -0.97 points faster decline in 3MSE per year (95% confidence interval (CI): -1.32, -0.63) compared to the participants with good balance. There was no association of balance and change in 3MSE among adults aged <76years (P value for balance and age interaction < 0.0001). DSST scores reflected -0.21 (95% CI: -0.37, -0.05) points greater decline when adjusted for co-variates. In Cox proportional hazard models, participants with worse balance had a higher risk of being cognitively impaired over the 6 years of follow-up visits (adjusted HR:1.72, 95% CI: 1.30, 2.29).CONCLUSIONS: Future studies should evaluate standing balance as a potential screening technique to identify individuals at risk of cognitive decline. Furthermore, a better understanding of the pathophysiological link between balance and cognition may inform strategies to prevent cognitive decline.

  View details for DOI 10.1093/ageing/afab038

  View details for PubMedID 33693525

• Aging-Related Changes in the Association between Negative Affect and Response Time Inconsistency in Older Adulthood. International journal of behavioral development Cerino, E. S., Stawski, R. S., Settersten, R. A., Odden, M. C., Hooker, K. 2021; 45 (2): 109-121

  Abstract

  Negative affect (NA) and positive affect (PA) are established modifiable psychosocial correlates of cognitive health and have demonstrated capacity for meaningful within-person fluctuations based on person-environment interactions, age, and measurement approach. Previous research has shown NA is associated with increased response time inconsistency (RTI), an early performance-based indicator of cognitive health and aging. It is unclear, however, whether PA is associated with RTI, and whether affect-RTI associations exist within persons over time or change as individuals get older. We utilized data from a measurement burst study (Cognition, Health and Aging Project) to explore within- and between-person associations between affect and RTI in community-dwelling older adults (N=111, M=80.04 years, SD=6.30). Affect and RTI were assessed on six days over a two-week period, every six months for two years. Results revealed a significant association between NA-low arousal and RTI within persons over time. RTI was higher on sessions when NA-low arousal was higher than usual (b=0.21, 95%CI=0.08 to 0.35, p<.01). This association decreased in magnitude over time (b=-0.09, 95%CI=-0.14 to - 0.03, p<.001), ultimately resulting in increased NA-low arousal being associated with decreased RTI two years later (b=-.14, 95%CI=-0.27 to -0.01, p<.05). No PA-RTI associations emerged. The results suggest efforts focused on maximizing resource allocation and personalizing cognitive health efforts should consider for whom and when mitigating NA may be maximally beneficial to daily cognition, whereas additional work is needed to determine influences from PA.

  View details for DOI 10.1177/0165025420937081

  View details for PubMedID 33758448

  View details for PubMedCentralID PMC7984415

• Subclinical Vascular Disease Burden and Premature Mortality Among Middle-aged Adults: the Atherosclerosis Risk in Communities Study. Journal of general internal medicine Wu, C. n., Zhang, K. n., Odden, M. C., Kucharska-Newton, A. M., Palta, P. n., Matsushita, K. n., Gottesman, R. F., Windham, B. G. 2021

  Abstract

  Whether high burden of subclinical vascular disease (SVD) is associated with increased premature mortality among middle-aged adults is not adequately understood. The association of midlife SVD burden with premature mortality among middle-aged adults free of clinical cardiovascular disease (CVD) could provide further insights into stratifying premature death beyond clinical CVD.To determine whether high burden of subclinical vascular disease is associated with increased premature mortality among middle-aged adults.We leveraged data from the Atherosclerosis Risk in Communities Study.Thirteen thousand eight hundred seventy-six community-dwelling blacks and whites aged 45-64 years from the Atherosclerosis Risk in Communities Study.Each SVD measure-ankle-brachial index, carotid intima-media thickness, and electrocardiogram-was scored 0 (no abnormalities), 1 (minor abnormalities), or 2 (major abnormalities). An index was constructed as the sum of three measures, ranging from 0 (lowest burden) to 6 (highest burden). We used the Cox proportional-hazards model to determine the association of SVD burden with premature mortality (death before age 70) among persons free of clinical CVD. We then tested the difference in point estimates between SVD and clinical CVD.Among persons without CVD, the premature death was 1.7, 2.1, 2.5, and 3.8 per 1000 person-years among those with an SVD score of 0 (lowest burden), 1, 2, and 3-6 (highest burden), respectively. After multivariable-adjustment, highest SVD burden (score = 3-6; HR = 1.47) was significantly associated with premature death among persons initially without CVD. In the model where persons with and without CVD were included, high SVD burden (score: 3-6 vs. 0) and CVD did not have hugely different association with premature death (HR = 1.49 vs. 1.68; P = 0.32 for comparison).Midlife SVD burden was associated with premature mortality and it could stratify premature death beyond clinical CVD. It is important to take SVD into account when designing interventions for reducing premature mortality.

  View details for DOI 10.1007/s11606-020-06398-6

  View details for PubMedID 33469773

• The timed 25-foot walk in a large cohort of multiple sclerosis patients. Multiple sclerosis (Houndmills, Basingstoke, England) Kalinowski, A., Cutter, G., Bozinov, N., Hinman, J. A., Hittle, M., Motl, R., Odden, M., Nelson, L. M. 2021: 13524585211017013

  Abstract

  The timed 25-foot walk (T25FW) is a key clinical outcome measure in multiple sclerosis patient management and clinical research.To evaluate T25FW performance and factors associated with its change in the Multiple Sclerosis Outcome Assessments Consortium (MSOAC) Placebo Database (n = 2465).We created confirmed disability progression (CDP) variables for T25FW and Expanded Disability Status Scale (EDSS) outcomes. We used intraclass correlation coefficients (ICCs) and Bland Altman plots to evaluate reliability. We evaluated T25FW changes and predictive validity using a mixed-effects model, survival analysis, and nested case-control analysis.The mean baseline score for the T25FW in this study population was 9.2 seconds, median = 6.1 (standard deviation = 11.0, interquartile range (IQR) = 4.8, 9.0). The T25FW measure demonstrated excellent test-retest reliability (ICC = 0.98). Walk times increased with age, disability, disease type, and disease duration; relapses were not associated with an increase. Patients with T25FW progression had a faster time to EDSS-CDP compared to those without (hazards ratio (HR): 2.6; confidence interval (CI): 2.2, 3.1). Changes in the T25FW were more likely to precede changes in EDSS.This research confirms the association of the T25FW with disability and provides some evidence of predictive validity. Our findings support the continued use of the T25FW in clinical practice and clinical trials.

  View details for DOI 10.1177/13524585211017013

  View details for PubMedID 34100297

• UNBIASED PROTEOMICS AND TARGETED BIOMARKERS ASSOCIATED WITH EXCEPTIONAL LONGEVITY AND MULTIMORBIDITY IN HUMANS Odden, M. OXFORD UNIV PRESS. 2021: 346

  View details for Web of Science ID 000842009901595

• CREATION AND VALIDATION OF A POLYSOCIAL SCORE FOR MORTALITY AMONG COMMUNITY-DWELLING OLDER ADULTS IN THE UNITED STATES Wu, C., Odden, M., Stawski, R., Magid, H. OXFORD UNIV PRESS. 2021: 162

  View details for Web of Science ID 000842009900626

• BLOOD PRESSURE CONTROL AND CARDIOVASCULAR AND MORTALITY RISK IN VA NURSING HOME RESIDENTS Liu, X., Lee, S., Steinman, M., Graham, L., Li, Y., Jing, B., Odden, M. OXFORD UNIV PRESS. 2021: 605

  View details for Web of Science ID 000842009903012

• BLOOD PRESSURE VARIABILITY AND COMPLEXITY IN NURSING HOME RESIDENTS BEFORE DEATH Graham, L., Lee, S., Steinman, M., Peralta, C., Rubinsky, A., Jing, B., Fung, K., Odden, M. OXFORD UNIV PRESS. 2021: 137

  View details for Web of Science ID 000842009900534

• DEPRESCRIBING BLOOD PRESSURE TREATMENT IN VA LONG-TERM CARE RESIDENTS Odden, M., Lee, S., Steinman, M., Rubinsky, A., Jing, B., Fung, K., Graham, L., Peralta, C. OXFORD UNIV PRESS. 2021: 333

  View details for Web of Science ID 000842009901547

• Association of Retail Environment and Neighborhood Socioeconomic Status with Mortality among Community-dwelling Older Adults in the US: Cardiovascular Health Study. The journals of gerontology. Series A, Biological sciences and medical sciences Zhang, K., Lovasi, G. S., Odden, M. C., Michael, Y. L., Newman, A. B., Arnold, A. M., Kim, D. H., Wu, C. 2021

  Abstract

  Few studies have examined the association of neighborhood environment and mortality among community-dwelling older populations. Geographic Information Systems (GIS)-based measures of neighborhood physical environment may provide new insights on the health effects of the social and built environment.We studied 4,379 community-dwelling older adults in the US aged ≥65 years from the Cardiovascular Health Study. Principal component analysis was used to identify neighborhood components from 48 variables assessing facilities and establishments, demographic composition, socio-economic status, and economic prosperity. We used a Cox model to evaluate the association of neighborhood components with five-year mortality. Age, sex, race, education, income, marital status, body mass index, smoking status, disability, coronary heart disease, and diabetes were included as covariates. We also examined the interactions between neighborhood components and sex and race (Black vs. white or other).We identified five neighborhood components, representing facilities and resources, immigrant communities, community-level economic deprivation, resident-level socio-economic status and residents' age. Communities' economic deprivation and residents' socio-economic status were significantly associated with five-year mortality. We did not find interactions between sex or race and any of the five neighborhood components. The results were similar in a sensitivity analysis where we used ten-year mortality as the outcome.We found that communities' economic status but not facilities in communities was associated with mortality among older adults. These findings revealed the importance and benefits living in a socio-economically advantaged neighborhood could have on health among older residents with different demographic backgrounds.

  View details for DOI 10.1093/gerona/glab319

  View details for PubMedID 34669918

• Genome-wide meta-analysis of muscle weakness identifies 15 susceptibility loci in older men and women. Nature communications Jones, G., Trajanoska, K., Santanasto, A. J., Stringa, N., Kuo, C., Atkins, J. L., Lewis, J. R., Duong, T., Hong, S., Biggs, M. L., Luan, J., Sarnowski, C., Lunetta, K. L., Tanaka, T., Wojczynski, M. K., Cvejkus, R., Nethander, M., Ghasemi, S., Yang, J., Zillikens, M. C., Walter, S., Sicinski, K., Kague, E., Ackert-Bicknell, C. L., Arking, D. E., Windham, B. G., Boerwinkle, E., Grove, M. L., Graff, M., Spira, D., Demuth, I., van der Velde, N., de Groot, L. C., Psaty, B. M., Odden, M. C., Fohner, A. E., Langenberg, C., Wareham, N. J., Bandinelli, S., van Schoor, N. M., Huisman, M., Tan, Q., Zmuda, J., Mellstrom, D., Karlsson, M., Bennett, D. A., Buchman, A. S., De Jager, P. L., Uitterlinden, A. G., Volker, U., Kocher, T., Teumer, A., Rodriguez-Manas, L., Garcia, F. J., Carnicero, J. A., Herd, P., Bertram, L., Ohlsson, C., Murabito, J. M., Melzer, D., Kuchel, G. A., Ferrucci, L., Karasik, D., Rivadeneira, F., Kiel, D. P., Pilling, L. C. 2021; 12 (1): 654

  Abstract

  Low muscle strength is an important heritable indicator of poor health linked to morbidity and mortality in older people. In a genome-wide association study meta-analysis of 256,523 Europeans aged 60 years and over from 22 cohorts we identify 15 loci associated with muscle weakness (European Working Group on Sarcopenia in Older People definition: n=48,596 cases, 18.9% of total), including 12 loci not implicated in previous analyses of continuous measures of grip strength. Loci include genes reportedly involved in autoimmune disease (HLA-DQA1 p=4*10-17), arthritis (GDF5 p=4*10-13), cell cycle control and cancer protection, regulation of transcription, and others involved in the development and maintenance of the musculoskeletal system. Using Mendelian randomization we report possible overlapping causal pathways, including diabetes susceptibility, haematological parameters, and the immune system. We conclude that muscle weakness in older adults has distinct mechanisms from continuous strength, including several pathways considered to be hallmarks of ageing.

  View details for DOI 10.1038/s41467-021-20918-w

  View details for PubMedID 33510174

• Recovery from Mobility Limitation in Middle Aged African Americans: the Jackson Heart Study. The journals of gerontology. Series A, Biological sciences and medical sciences Odden, M. C., Sims, K. D., Thorpe, R. J., Sims, M., Dhamoon, M., Min, Y., Correa, A. 2020

  Abstract

  BACKGROUND: Despite evidence that African Americans shoulder a high burden of mobility limitation, little is known about factors associated with recovery.METHODS: Participants from the Jackson Heart Study underwent three in-person exams from 2000-2013. Mobility limitations were assessed over this period by self-reported limitations in walking half a mile or climbing stairs during annual phone calls. The outcome of interest, recovery from mobility limitation, was defined as no mobility limitation the year following an incident event. Candidate predictor variables were assessed in logistic regression models, including sociodemographic, psychosocial, and health measures. Inverse probability weights were used to address missing data in the outcome.RESULTS: Among 4,526 participants [mean (SD) age = 54.5 (12.8) years] without a mobility limitation at baseline, 1,445 (32%) had an incident mobility limitation over 12 years of follow-up, and 709 (49%) reported recovery from mobility limitation by one year later. Low income and daily discrimination were associated with a lower likelihood of recovery even after adjustment for covariates. In adjusted models, greater comorbidity was associated with a lower likelihood of recovering (p-value for trend = 0.05). History of heart failure and cancer were associated with a lower likelihood of recovering from mobility limitation (OR: 0.52, 95% CI: 0.29, 0.94 and 0.74, 95% CI: 0.55, 1.00). Adiposity, smoking status, and physical activity were not associated with recovery from mobility limitation.CONCLUSION: Half of incident mobility limitations in this population of middle-aged African Americans were transient. Adverse sociodemographic factors and comorbidities were associated with lower likelihood of recovery.

  View details for DOI 10.1093/gerona/glaa272

  View details for PubMedID 33075819

• Predicting Risk of Atherosclerotic Cardiovascular Disease Using Pooled Cohort Equations in Older Adults With Frailty, Multimorbidity, and Competing Risks. Journal of the American Heart Association Nguyen, Q. D., Odden, M. C., Peralta, C. A., Kim, D. H. 2020: e016003

  Abstract

  Background Assessment of atherosclerotic cardiovascular disease (ASCVD) risk is crucial for prevention and management, but the performance of the pooled cohort equations in older adults with frailty and multimorbidity is unknown. We evaluated the pooled cohort equations in these subgroups and the impact of competing risks. Methods and Results In 4249 community-dwelling adults, aged ≥65years, from the CHS (Cardiovascular Health Study), we calculated 10-year risk of hard ASCVD. Frailty was determined using the Fried phenotype. Latent class analysis was used to identify individuals with multimorbidity patterns using chronic conditions. We assessed discrimination using the C-statistic and calibration by comparing predicted ASCVD risks with estimated risk using cause-specific and cumulative incidence models, by multimorbidity patterns and frailty status. A total of 917 (21.6%) participants had an ASCVD event, and 706 (16.6%) had a competing event of death. C-statistic was 0.68 in men and 0.69 in women; calibration was good when compared with cause-specific and cumulative incidence estimated risks (males, -0.1% and 3.3%; females, 0.6% and 1.4%). Latent class analysis identified 4 patterns: minimal disease, cardiometabolic, low cognition, musculoskeletal-lung depression. In the cardiometabolic pattern, ASCVD risk was overpredicted compared with cumulative incidence risk in men (7.4%) and women (6.8%). Risk was underpredicted in men (-10.7%) and women (-8.2%) with frailty compared with cause-specific risk. Miscalibration occurred mostly at high predicted risk ranges. Conclusions ASCVD prediction was good in this cohort of adults aged ≥65years. Although calibration varied by multimorbidity patterns, frailty, and competing risks, miscalibration was mostly present at high predicted risk ranges and thus less likely to alter decision making for primary prevention therapy.

  View details for DOI 10.1161/JAHA.119.016003

  View details for PubMedID 32875939

• Conceiving of Questions Before Delivering Analyses: Relevant Question Formulation in Reproductive and Perinatal Epidemiology. Epidemiology (Cambridge, Mass.) Snowden, J. M., Reavis, K. M., Odden, M. C. 2020; 31 (5): 644–48

  View details for DOI 10.1097/EDE.0000000000001223

  View details for PubMedID 32501813

• Aging-related changes in the association between negative affect and response time inconsistency in older adulthood INTERNATIONAL JOURNAL OF BEHAVIORAL DEVELOPMENT Cerino, E. S., Stawski, R. S., Settersten, R. A., Odden, M. C., Hooker, K. 2020

  View details for DOI 10.1177/0165025420937081

  View details for Web of Science ID 000546373700001

• Results of the CARDIA study suggest that higher dietary potassium may be kidney protective KIDNEY INTERNATIONAL Elfassy, T., Zhang, L., Raij, L., Bibbins-Domingo, K., Lewis, C. E., Allen, N., Liu, K. J., Peralta, C. A., Odden, M. C., Al Hazzouri, A. 2020; 98 (1): 187–94

  View details for Web of Science ID 000542929400025

• Brachial Flow-mediated Dilation and Risk of Dementia: The Cardiovascular Health Study. Alzheimer disease and associated disorders Garg, P. K., Tan, A. X., Odden, M. C., Gardin, J. M., Lopez, O. L., Newman, A. B., Rawlings, A. M., Mukamal, K. J. 2020

  Abstract

  INTRODUCTION: Brachial flow-mediated dilation (FMD) is a physiologic measure of endothelial function. We determined the prospective association of brachial FMD with incident dementia among older adults.METHODS: We included 2777 Cardiovascular Health Study participants who underwent brachial FMD measurement. Incident dementia was ascertained by medication use, International Classification of Diseases-9 codes, requirement for a proxy, and death certificates and calibrated to gold-standard assessments performed in a subset of the cohort.RESULTS: Mean participant age at time of brachial FMD measurement was 77.9 years. We identified 1650 incident dementia cases (median follow-up=10.5y). After adjusting for age, race, sex, education, clinic site, and baseline arterial diameter, risk of dementia for participants in the highest quartile of percent brachial FMD did not differ from those in lowest quartile (hazard ratio=0.89, 95% confidence interval: 0.77, 1.03).CONCLUSIONS: Brachial FMD, measured late in life, is not associated with an increased risk of incident dementia.

  View details for DOI 10.1097/WAD.0000000000000394

  View details for PubMedID 32483019

• Association of High-Density Lipoprotein Cholesterol With Cognitive Function: Findings From the PROspective Study of Pravastatin in the Elderly at Risk. Journal of aging and health Grasset, L., Smit, R. A., Caunca, M. R., Elfassy, T., Odden, M. C., van der Grond, J., van Buchem, M. A., Stott, D. J., Sattar, N., Trompet, S., Jukema, J. W., Zeki Al Hazzouri, A. 2020: 898264320916959

  Abstract

  Objective: We aimed to examine whether variability in high-density lipoprotein cholesterol (HDL-c) over time was associated with cognitive function. Method: We conducted a post hoc analysis of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) trial. Our sample included 4,428 participants with at least two repeated HDL-c measures between Months 3 and 24 postbaseline and with cognitive assessments at Month 30. HDL-c variability was defined as the intraindividual standard deviation over each person's repeated measurements. Results: Higher HDL-c variability was associated with worse performance on the Letter-Digit Coding Test (beta [95% confidence interval] [CI] = -4.39 [-7.36, -1.43], p = .004), immediate recall on the 15-Picture Learning Test (beta [95% CI] = -0.98 [-1.86, -0.11], p = .027), and delayed recall on the 15-Picture Learning Test (beta [95% CI] = -1.90 [-3.14, -0.67], p = .002). The associations did not vary by treatment group. Discussion: Our findings suggest that variability in HDL-c may be associated with poor cognitive function among older adults.

  View details for DOI 10.1177/0898264320916959

  View details for PubMedID 32456512

• Level and change in N-terminal pro B-type Natriuretic Peptide and kidney function and survival to age 90. The journals of gerontology. Series A, Biological sciences and medical sciences Haberle, A. D., Biggs, M. L., Cushman, M., Psaty, B. M., Newman, A. B., Shlipak, M. G., Gottdiener, J., Wu, C., Gardin, J. M., Bansal, N., Odden, M. C. 2020

  Abstract

  BACKGROUND: Many traditional cardiovascular risk factors do not predict survival to very old age. Studies have shown associations of estimated glomerular filtration rate (eGFR) and N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) with cardiovascular disease and mortality in older populations. This study aimed to evaluate the associations of the level and change in eGFR and NT-pro-BNP with longevity to age 90 years.METHODS: The population included participants (n=3,645) in the Cardiovascular Health Study, aged between 67-75 at baseline. The main exposures were eGFR, calculated with the Berlin Initiative Study equation (BIS2), and NT-pro-BNP, and the main outcome was survival to age 90. Mixed models were used to estimate level and change of the main exposures.RESULTS: There was an association between baseline level and change of both eGFR and NT-pro-BNP and survival to 90, and this association persisted after adjustment for covariates. Each 10 ml/min per 1.73 m2 higher eGFR level was associated with an adjusted odds ratio (OR) of 1.23 (95% CI: 1.13, 1.34) of survival to 90, and a 0.5 ml/min/ 1.73 m2 slower decline in eGFR was associated with an OR of 1.51 (95% CI: 1.31, 1.74). A 2-fold higher level of NT-pro-BNP level had an adjusted OR of 0.67 (95% CI: 0.61, 0.73), and a 1.05-fold increase per year in NT-pro-BNP had an OR of 0.53 (95% CI: 0.43, 0.65) for survival to age 90.CONCLUSION: eGFR and NT-pro-BNP appear to be important risk factors for longevity to age 90.

  View details for DOI 10.1093/gerona/glaa124

  View details for PubMedID 32417919

• Functional health and white matter hyperintensities as effect modifiers of blood pressure-lowering on cognitive function and vascular events in older Secondary Prevention of Small Subcortical Strokes trial participants. Journal of hypertension Blum, M. R., Scherzer, R., Ikeme, J. C., Benavente, O. R., McClure, L. A., Peralta, C. A., Odden, M. C. 2020

  Abstract

  OBJECTIVE: To determine whether cerebral small vessel disease or disability modify the effect of SBP treatment on cognitive and vascular outcomes in older patients with recent lacunar stroke.METHODS: Participants aged at least 65 years of the Secondary Prevention of Small Subcortical Strokes Trial were randomized to a higher (130-149 mmHg) or lower (<130 mmHg) SBP target. The primary outcome was change in cognitive function (Cognitive Abilities Screening Instrument); secondary outcomes were incident mild cognitive impairment, stroke, major vascular events (all-stroke, myocardial infarction), and all-cause death. Results were stratified by severity of white matter hyperintensities (WMH; none/mild, moderate, severe) on baseline MRI, and by disability (no vs. at least one limitation in activities of daily living).RESULTS: One thousand, two hundred and sixty-three participants (mean age 73.8 ± 5.9 years, 40% women) were included. Participants with severe WMH or disability had worse cognitive function at baseline and after a mean follow-up of 3.9 years. No significant interactions existed between treatment group and effect modifiers (WMH, disability) for change in cognitive function (P for interaction 0.42 and 0.66, respectively). A lower SBP target appeared more beneficial among those with worse WMH burden for vascular outcomes (P for interaction = 0.01 for stroke and 0.03 for major vascular events).CONCLUSION: There was no difference in the effect of lowering SBP to less than 130 mmHg on cognitive function by cerebral small vessel disease or disability among older adults with a history of lacunar stroke. Those with evidence of small vessel disease may derive greater benefit from lower SBP on prevention of subsequent vascular events.TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00059306.

  View details for DOI 10.1097/HJH.0000000000002440

  View details for PubMedID 32371759

• Association of Racial Residential Segregation Throughout Young Adulthood and Cognitive Performance in Middle-aged Participants in the CARDIA Study. JAMA neurology Caunca, M. R., Odden, M. C., Glymour, M. M., Elfassy, T., Kershaw, K. N., Sidney, S., Yaffe, K., Launer, L., Zeki Al Hazzouri, A. 2020

  Abstract

  Importance: Neighborhood-level residential segregation is implicated as a determinant for poor health outcomes in black individuals, but it is unclear whether this association extends to cognitive aging, especially in midlife.Objective: To examine the association between cumulative exposure to residential segregation during 25 years of young adulthood among black individuals and cognitive performance in midlife.Design, Setting, and Participants: The ongoing prospective cohort Coronary Artery Risk Development in Young Adults (CARDIA) Study recruited 5115 black and white participants aged 18 to 30 years from 4 field centers at the University of Alabama, Birmingham; University of Minnesota, Minneapolis; Northwestern University, Chicago, Illinois; and Kaiser Permanente, Oakland, California. Data were acquired from February 1985 to May 2011. Among the surviving CARDIA cohort, 3671 (71.8%) attended examination year 25 of the study in 2010, when cognition was measured, and 3008 (81.9%) of those completed the cognitive assessments. To account for time-varying confounding and differential censoring, marginal structural models using inverse probability weighting were applied. Data were analyzed from April 16 to July 20, 2019.Main Outcomes and Measures: Racial residential segregation was measured using the Getis-Ord Gi* statistic, and the mean cumulative exposure to segregation was calculated across 6 follow-up visits from baseline to year 25 of the study, then categorized into high, medium, and low segregation. Cognitive function was measured at year 25 of the study, using the Digit Symbol Substitution Test (DSST), Stroop color test (reverse coded), and Rey Auditory Verbal Learning Test. To facilitate comparison of estimates, z scores were calculated for all cognitive tests.Results: A total of 1568 black participants with available cognition data were included in the analysis. At baseline, participants had a mean (SD) age of 25 (4) years and consisted of 936 women (59.7%). Greater cumulative exposure to segregated neighborhoods was associated with a worse DSST z score (for high segregation, beta=-0.37 [95% CI, -0.61 to -0.13]; for medium segregation, beta=-0.25 [95% CI, -0.51 to 0.0002]) relative to exposure to low segregation.Conclusions and Relevance: In this cohort study, exposure to residential segregation throughout young adulthood was associated with worse processing speed among black participants as early as in midlife. This association may potentially explain black-white disparities in dementia risk at older age.

  View details for DOI 10.1001/jamaneurol.2020.0860

  View details for PubMedID 32364578

• Patterns of Cardiovascular Risk Factors in Old Age and Survival and Health Status at 90. The journals of gerontology. Series A, Biological sciences and medical sciences Odden, M. C., Rawlings, A. M., Arnold, A. M., Cushman, M., Biggs, M. L., Psaty, B. M., Newman, A. B. 2020

  Abstract

  BACKGROUND: The population age 90 years and older is the fastest growing segment of the U.S. population. Only recently is it possible to study the factors that portend survival to this age.METHODS: Among participants of the Cardiovascular Health Study, we studied the association of repeated measures of cardiovascular risk factors measured over 15-23 years of follow-up and not only survival to 90 years of age, but also healthy aging outcomes among the population who reached age 90. We included participants aged 67-75 years at baseline (n = 3,613/5,888) to control for birth cohort effects, and followed participants until death or age 90 (median follow-up = 14.7 years).RESULTS: Higher systolic blood pressure was associated with a lower likelihood of survival to age 90, although this association was attenuated at older ages (p-value for interaction <.001) and crossed the null for measurements taken in participants' 80's. Higher levels of high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and body mass index (BMI) were associated with greater longevity. Among the survivors to age 90, those with worse cardiovascular profile (high blood pressure, LDL cholesterol, glucose, and BMI; low HDL cholesterol) had lower likelihood of remaining free of cardiovascular disease, cognitive impairment, and disability.CONCLUSION: In summary, we observed paradoxical associations between some cardiovascular risk factors and survival to old age; whereas, among those who survive to very old age, these risk factors were associated with higher risk of adverse health outcomes.

  View details for DOI 10.1093/gerona/glaa043

  View details for PubMedID 32267489

• A prospective cohort study of in utero and early childhood arsenic exposure and infectious disease in 4- to 5-year-old Bangladeshi children. Environmental epidemiology (Philadelphia, Pa.) Ahmed, S. M., Branscum, A., Welch, B. M., Megowan, M., Bethel, J. W., Odden, M. C., Joya, S. A., Ibn Hasan, M. O., Lin, P., Mostofa, G., Quamruzzaman, Q., Rahman, M., Christiani, D. C., Kile, M. L. 2020; 4 (2): e086

  Abstract

  Background: Previous research found that infants who were exposed to high levels of arsenic in utero had an increased risk of infectious disease in the first year of life. This prospective study examined the association between arsenic exposures during gestation, and respiratory, diarrheal, and febrile morbidity in children 4-5 years of age.Methods: A cohort of pregnant women was recruited in 2008-2011 in Bangladesh. Their children (N = 989) were followed, and household drinking water samples were collected during pregnancy, toddlerhood (12-40 months of age), and childhood (4-5 years of age). We actively surveyed mothers every 2 weeks regarding their children's infectious diseases symptoms from 4 to 5 years of age. Poisson regression models were used to estimate the association between arsenic exposure and respiratory and febrile illness.Results: Median drinking water arsenic was 4.6, 8.8, and 4.2 g/L in pregnancy, toddlerhood, and childhood, respectively. We observed 0.01, 1.2, and 1.0 cases per 100 person-days of diarrhea, respiratory, and febrile illness, respectively. The incident rate ratios (IRRs) for each doubling of drinking water arsenic during pregnancy were 1.10 (95% confidence interval [CI] = 1.00, 1.22) and 0.93 (95% CI = 0.82, 1.05) for respiratory and febrile illness, respectively, after adjusting for covariates. The association between arsenic exposure measured during toddlerhood and childhood was attenuated and not significantly associated with either outcome. Diarrheal disease was too infrequent to assess.Conclusions: Drinking water arsenic exposure during pregnancy was associated with a higher risk of acute respiratory infections in children 4-5 years old in Bangladesh.

  View details for DOI 10.1097/EE9.0000000000000086

  View details for PubMedID 32656486

• Generalizability of Clinical Trials Supporting the 2017 American College of Cardiology/American Heart Association Blood Pressure Guideline. JAMA internal medicine Anderson, T. S., Odden, M., Penko, J., Kazi, D. S., Bellows, B. K., Bibbins-Domingo, K. 2020

  View details for DOI 10.1001/jamainternmed.2020.0051

  View details for PubMedID 32176252

• Linking early life risk factors to frailty in old age: evidence from the China Health and Retirement Longitudinal Study. Age and ageing Li, Y., Xue, Q., Odden, M. C., Chen, X., Wu, C. 2020

  Abstract

  BACKGROUND: exposures in childhood and adolescence may impact the development of diseases and symptoms in late life. However, evidence from low- and middle-income countries is scarce. In this cross-sectional study, we examined the association of early life risk factors with frailty amongst older adults using a large, nationally representative cohort of community-dwelling Chinese sample.METHODS: we included 6,806 participants aged $\ge$60years from the China Health and Retirement Longitudinal Study. We measured 13 risk factors in childhood or adolescence through self-reports, encompassing six dimensions (education, family economic status, nutritional status, domestic violence, neighbourhood and health). We used multinomial regression models to examine the association between risk factors and frailty. We further calculated the absolute risk difference for the statistically significant factors.RESULTS: persons with higher personal and paternal education attainment, better childhood neighbourhood quality and better childhood health status had lower risk of being frail in old age. Severe starvation in childhood was associated with higher risk of prefrailty. The risk differences of being frail were 5.6% lower for persons with a high school or above education, 1.5% lower for those whose fathers were literate, 4.8% lower for the highest neighbourhood quality and 2.9% higher for worse childhood health status compared to their counterparts.CONCLUSIONS: unfavorable socioeconomic status and worse health condition in childhood and adolescence may increase the risk of late-life frailty amongst Chinese older adults.

  View details for DOI 10.1093/ageing/afz160

  View details for PubMedID 31957780

• Daily linkages among high and low arousal affect and subjective cognitive complaints. Aging & mental health Cerino, E. S., Hooker, K., Settersten, R. A., Odden, M. C., Stawski, R. S. 2020: 1–12

  Abstract

  Objectives: Subjective cognitive complaints may be an early indicator of Alzheimer's disease pathology and related dementias that can be detectable prior to objective, performance-based decline. Negative and positive affective states (NA and PA, respectively) are established psychosocial correlates of cognition in older adulthood and have demonstrated capacity for meaningful within-person fluctuations based on person-environment interactions, age, and measurement approach.Method: We utilized data from a 100-day, microlongitudinal study of 105 community-dwelling older adults (Mage = 63.19, SD = 7.80, Range = 52-88) to explore within- and between-person associations between high and low arousal NA and PA, and memory- and attention-related complaints.Results: For memory-related complaints, those who reported experiencing greater NA-high arousal had increased forgetfulness (OR = 2.23, 95%CI: 1.11-4.49, p < .05). Within persons, reporting more NA-high arousal than usual was associated with increased forgetfulness (OR = 1.01, 95%CI: 1.004-1.018, p < .01). For attention-related complaints, those who reported experiencing greater NA-low arousal had increased trouble staying focused (OR = 2.34, 95%CI: 1.17-4.66, p < .05). Within persons, reporting more NA-low arousal (OR = 1.02, 95%CI: 1.01-1.03, p < .001) and less PA-high arousal (OR = 0.96, 95%CI: 0.95-0.97, p < .001) than usual was associated with increased trouble staying focused. Additionally, reporting more PA-low arousal than usual was associated with decreased trouble staying focused among those with higher levels of conscientiousness (OR = 0.72, 95%CI: 0.57-0.92, p < .01).Conclusion: Results from this study offer a means to maximize resource allocation and personalized cognitive health efforts by pinpointing for whom and on which days boosting PA and/or reducing NA may both serve as pathways to benefit daily subjective cognition.

  View details for DOI 10.1080/13607863.2020.1711863

  View details for PubMedID 31933378

• The association of prediagnosis social support with survival after heart failure in the Cardiovascular Health Study. Annals of epidemiology Kaiser, P., Allen, N., Delaney, J. A., Hirsch, C. H., Carnethon, M., Arnold, A. M., Odden, M. C. 2020

  Abstract

  PURPOSE: Although social support has been shown to be associated with survival among persons with cardiovascular disease, little research has focused on whether social support, measured before the onset of heart failure, can enhance survival after diagnosis. The objective of this study was to assess the association between prediagnosis social support and postdiagnosis survival among older adults with heart failure.METHODS: We obtained the data from the Cardiovascular Health Study, which included noninstitutionalized adults aged 65 years or older from four sites in the United States with primary enrollment in 1989-1990. We used two measures of social support, the Lubben Social Network Scale and the Interpersonal Support Evaluation List. The analytic data set included 529 participants with a social support measure within two years before diagnosis of heart failure.RESULTS: After adjustment for demographic covariates, cardiovascular risk factors, and general health status, mortality rates were lower among participants in the highest tertile of social network scores (HR 0.74, 95% CI: 0.59, 0.93) and the middle tertile (HR 0.73 [0.58, 0.90]), compared with the lowest tertile. Results with interpersonal support were null.CONCLUSIONS: These findings suggest that prediagnosis structural social support may modestly buffer heart failure patients from mortality.

  View details for DOI 10.1016/j.annepidem.2019.12.013

  View details for PubMedID 31992494

• Results of the CARDIA study suggest that higher dietary potassium may be kidney protective. Kidney international Elfassy, T. n., Zhang, L. n., Raij, L. n., Bibbins-Domingo, K. n., Lewis, C. E., Allen, N. B., Liu, K. J., Peralta, C. A., Odden, M. C., Zeki Al Hazzouri, A. n. 2020

  Abstract

  The association between dietary sodium and potassium intake with the development of kidney disease remains unclear, particularly among younger individuals. Here, we determined whether dietary sodium and potassium intake are associated with incident chronic kidney disease (CKD) using data from 1,030 adults (age 23-35 in 1990-1991) from the Coronary Artery Risk Development In Young Adults study, based on repeated measurements of estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (ACR) from 1995 through 2015. Urinary sodium and potassium excretion (mg/day), calculated from three 24-hour urine collections in 1990-1991, were averaged to measure sodium and potassium intake. Serum creatinine was used to calculate eGFR using the CKD EPI equation; spot urine albumin and creatinine were used to calculate ACR, each at five visits from 1995-1996 through 2015-2016. CKD was defined as decreased eGFR (under 60 ml/min/1.73m2) or the development of albuminuria (ACR over 30 mg/g). We used log binomial regression models adjusted for socio-demographic, behavioral, and clinical factors to determine whether sodium and potassium intake were associated with incident CKD (decreased eGFR or developed albuminuria) among those free of CKD in 1995. Dietary sodium intake was not significantly associated with incident CKD. However, every 1,000 mg/day increment of potassium intake in 1990 was significantly associated with a 29% lower risk of incident albuminuria (relative risk 0.71, 95% confidence interval 0.53, 0.95), but not eGFR. Thus, higher dietary potassium intake may protect against the development of kidney damage, particularly albuminuria.

  View details for DOI 10.1016/j.kint.2020.02.037

  View details for PubMedID 32471640

• The Difference Between Cystatin C and Creatinine-Based Estimated GFR and Incident Frailty: An Analysis of the Cardiovascular Health Study (CHS). American journal of kidney diseases : the official journal of the National Kidney Foundation Potok, O. A., Phil, R. K., Bansal, N. n., Siscovick, D. S., Odden, M. n., Ix, J. H., Shlipak, M. G., Rifkin, D. E. 2020

  View details for DOI 10.1053/j.ajkd.2020.05.018

  View details for PubMedID 32682698

• Perceived Discrimination and Trajectories of C-Reactive Protein: The Jackson Heart Study. American journal of preventive medicine Sims, K. D., Sims, M., Glover, L. M., Smit, E., Odden, M. C. 2019

  Abstract

  INTRODUCTION: Perceiving discriminatory treatment may contribute to systemic inflammation, a risk factor of cardiovascular pathophysiology. This study evaluated the association of self-reported discrimination with changes in high-sensitivity C-reactive protein and the mediating role of adiposity.METHODS: The sample included 5,145 African-Americans, aged 21-92 years, in the Jackson Heart Study. Everyday, lifetime, and burden from perceived discrimination comprised primary predictors in 3 sets of multivariable linear regression models of baseline (2000-2004) discrimination and natural logarithm of high-sensitivity C-reactive protein. Multivariable linear mixed models assessed mean changes in natural logarithm of high-sensitivity C-reactive protein over the study period (2000-2013). Mediation was quantified by percentage changes in estimates adjusted for BMI, waist circumference, and waist-to-height ratio. Multiple imputation addressed missingness in baseline covariates and in high-sensitivity C-reactive protein taken at all 3 study examinations. Analyses were conducted in 2018.RESULTS: In cross-sectional analyses, male participants in the middle and highest tertiles of lifetime discrimination had natural logarithm of high-sensitivity C-reactive protein levels that were 0.13 (95% CI= -0.24, -0.01) and 0.15 (95% CI= -0.27, -0.02) natural logarithm(mg/dL) lower than those in the lowest tertile. In longitudinal analyses, all participants reporting more frequent everyday discrimination had a 0.07 natural logarithm(mg/dL) greater increase in natural logarithm of high-sensitivity C-reactive protein per examination than those reporting none (95% CI=0.01, 0.12). A similar trend emerged for lifetime discrimination and changes in natural logarithm of high-sensitivity C-reactive protein (adjusted mean increase per visit: 0.04 natural logarithm[mg/dL], 95% CI=0.01, 0.08). Adiposity did not mediate the longitudinal associations.CONCLUSIONS: Everyday and lifetime discrimination were associated with significant high-sensitivity C-reactive protein increases over 13 years. The physiologic response to discrimination may lead to systemic inflammation.

  View details for DOI 10.1016/j.amepre.2019.09.019

  View details for PubMedID 31831294

• Reply. Journal of hypertension Miller, L. M., Odden, M. C. 2019; 37 (12): 2501

  View details for DOI 10.1097/HJH.0000000000002260

  View details for PubMedID 31688296

• Machine Learning in Aging Research JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Odden, M. C., Melzer, D. 2019; 74 (12): 1901–2

  View details for DOI 10.1093/gerona/glz074

  View details for Web of Science ID 000501737700008

• Quantifying and Classifying Physical Resilience among Older Adults: The Health, Aging, and Body Composition Study. The journals of gerontology. Series A, Biological sciences and medical sciences Wu, C., Li, Y., Marron, M. M., Odden, M. C., Newman, A. B., Sanders, J. L. 2019

  Abstract

  BACKGROUND: The concept of resilience has gained increasing attention in aging research; however, current literature lacks consensus on how to measure resilience. We constructed a novel resilience measure based on the degree of mismatch between persons' frailty level and disease burden and examined its predictive validity. We also sought to explore the physiological correlates of resilience.METHODS: Participants were 2,457 older adults from the Health, Aging, and Body Composition Study. We constructed the resilience measure as the residual taken from the linear model regressing frailty on age, sex, race/ethnicity, 14 diseases, self-reported health, and number of medications. Participants were classified into three groups-adapters, expected agers, and premature frailers-based on residuals (less than, within, or above one standard deviation of the mean). Validation outcomes included years of able life (YAL), years of healthy life (YHL), years of healthy and able life (YHAL), disability, hospitalization, and survival.RESULTS: The average YHAL was 5.1, 7.7, and 9.1 years among premature frailers, expected agers, and adapters, respectively. Compared with premature frailers and expected agers, adapters had significantly lower rates of disability, hospitalization, and mortality and higher proportion surviving to 90 years. The likelihood of surviving to 90 years was 20.4%, 30.6%, and 39.7% among premature frailers, expected agers, and adapters.CONCLUSIONS: We developed and validated a novel approach for quantifying and classifying physical resilience in a cohort of well-functioning white and black older adults. Persons with high physical resilience level had longer healthy life span and lower rates of adverse outcomes.

  View details for DOI 10.1093/gerona/glz247

  View details for PubMedID 31628840

• Heterogeneous Exposure Associations in Observational Cohort Studies: The Example of Blood Pressure in Older Adults. American journal of epidemiology Odden, M. C., Rawlings, A. M., Khodadadi, A., Fern, X., Shlipak, M. G., Bibbins-Domingo, K., Covinsky, K., Kanaya, A. M., Lee, A., Haan, M. N., Newman, A. B., Psaty, B. M., Peralta, C. A. 2019

  Abstract

  Heterogeneous exposure associations (HEAs) can be defined as differences in the association of a exposure with an outcome among subgroups that differ by a set of characteristics. This manuscript intends to foster discussion of HEAs in the epidemiological literature, and present a variant of the random forest algorithm that can be used to identify HEAs. We demonstrate the use of this algorithm in the setting of the association of systolic blood pressure and death in older adults. The training set included pooled data from the baseline examination of the Cardiovascular Health Study (1989-1993), the Health, Aging, and Body Composition study (1997-1998), and the Sacramento Area Latino Study on Aging (1998-1999). The test set included data from the National Health and Nutrition Examination Survey (1999-2002). The hazard ratios ranged from 1.25 (95% CI: 1.13, 1.37) per 10 mmHg higher systolic blood pressure in men aged ≤67 years with diastolic blood pressure >80 mmHg, to 1.00 (0.96, 1.03) in women with creatinine <0.7 mg/dL and a history of hypertension. HEAs have the potential to improve our understanding of disease mechanisms in diverse populations, and guide the design of randomized controlled trials to control exposures in heterogeneous populations.

  View details for DOI 10.1093/aje/kwz218

  View details for PubMedID 31595960

• Development and validation of a novel measure of resilience in older adults: a longitudinal cohort study Wu, C., Li, Y., Marron, M. M., Odden, M. C., Newman, A. B., Sanders, J. L. ELSEVIER SCIENCE INC. 2019: 10

  View details for Web of Science ID 000490981600011

• The role of functional status on the relationship between blood pressure and cognitive decline: the Cardiovascular Health Study JOURNAL OF HYPERTENSION Miller, L. M., Peralta, C. A., Fitzpatrick, A. L., Wu, C., Psaty, B. M., Newman, A. B., Odden, M. C. 2019; 37 (9): 1790–96

  View details for DOI 10.1097/HJH.0000000000002102

  View details for Web of Science ID 000501621900008

• Machine Learning in Aging Research. The journals of gerontology. Series A, Biological sciences and medical sciences Odden, M. C., Melzer, D. 2019

  View details for PubMedID 30903146

• Trajectories of Nonagenarian Health: Sex, Age, and Period Effects AMERICAN JOURNAL OF EPIDEMIOLOGY Odden, M. C., Koh, W., Arnold, A. M., Rawlings, A. M., Psaty, B. M., Newman, A. B. 2019; 188 (2): 382–88

  View details for DOI 10.1093/aje/kwy241

  View details for Web of Science ID 000460620100014

• The role of functional status on the relationship between blood pressure and cognitive decline: the Cardiovascular Health Study. Journal of hypertension Miller, L. M., Peralta, C. A., Fitzpatrick, A. L., Wu, C. n., Psaty, B. M., Newman, A. B., Odden, M. C. 2019

  Abstract

  To examine whether self-reported functional status modified the association between blood pressure (BP) and cognitive decline among older adults.The study included 2097 US adults aged 75 years and older from the Cardiovascular Health Study, followed for up to 6 years. Functional status was ascertained by self-reported limitation in activities of daily living (ADL; none vs. any). Cognitive function was assessed by the Modified Mini Mental State Exam (3MSE). We used linear mixed models to examine whether the presence of at least one ADL limitation modified the association between BP and cognitive decline. Potential confounders included demographics, physiologic measures, antihypertensive medication use and apolipoprotein E ε4 allele. We conducted stratified analyses for significant interactions between BP and ADL.The association between BP and change in 3MSE differed by baseline ADL limitation. Among participants without ADL limitation, elevated systolic BP (≥140 mmHg) was associated with a 0.15 decrease (95% CI -0.24 to -0.07); P value for interaction less than 0.001, whereas in those with an ADL limitation, elevated systolic BP was independently associated with a 0.30 increase in 3MSE scores per year (95% CI 0.06-0.55). Elevated diastolic BP (≥80 mmHg) was associated with an increase in cognitive function in both groups, although the increase was greater in those with ADL limitation (0.47 points per year vs. 0.18 points per year, P value for interaction = 0.01).Elevated BP appears to be associated with a decrease in cognitive scores among functioning older adults, and modest improvements in cognitive function among poorly functioning elders.

  View details for PubMedID 31058794

• Sex Differences in the Association Between Pentraxin 3 and Cognitive Decline: The Cardiovascular Health Study. The journals of gerontology. Series A, Biological sciences and medical sciences Miller, L. M., Jenny, N. S., Rawlings, A. M., Arnold, A. M., Fitzpatrick, A. L., Lopez, O. L., Odden, M. C. 2019

  Abstract

  The importance of systemic inflammation, measured by C-reactive protein, in cognitive decline has been demonstrated; however, the role of vascular inflammation is less understood. Pentraxin 3 (PTX3) is a novel marker of vascular inflammation.We followed adults 65 and older, free of cardiovascular disease (CVD) for up to 9 years (n = 1,547) in the Cardiovascular Health Study. We evaluated the relationship between PTX3 and change in cognitive function, measured using the Modified Mini-Mental State Examination (3MSE), and incident cognitive impairment (3MSE < 80). Mediation by CVD events, and effect modification by sex and apolipoprotein E ɛ4 allele (APOE4) were also examined.The average decline in 3MSE was 0.77 points per year. The association between PTX3 and change in 3MSE differed between women and men (p = .02). In the adjusted model, each standard deviation higher in PTX3 was associated with a 0.20 greater decline in 3MSE score per year in women over follow-up (95% CI: -0. 37, -0.03; p = .02), compared to no change in men (β = 0.07; 95% CI: -0.08, 0.22). CVD events had a minor effect on the associations. No effect modification by APOE4 was found, although we observed the association of PTX3 and cognitive impairment in women was attenuated and nonsignificant after adjustment for APOE4. There was a paradoxical protective association between PTX3 and reduced cognitive impairment in men, even after adjustment for APOE4.We found that vascular inflammation was significantly associated with cognitive decline in older women, but not men.

  View details for DOI 10.1093/gerona/glz217

  View details for PubMedID 31808814

• Perceived Discrimination and Trajectory of High-Sensitivity C-Reactive Protein: The Jackson Heart Study Sims, K. D., Sims, M., Glover, L., Smit, E., Odden, M. C. LIPPINCOTT WILLIAMS & WILKINS. 2019

  View details for DOI 10.1161/circ.139.suppl_1.P027

  View details for Web of Science ID 000478079000460

• Validation of the REGARDS Severe Sepsis Risk Score. Journal of clinical medicine Wang, H. E., Donnelly, J. P., Yende, S., Levitan, E. B., Shapiro, N. I., Dai, Y., Zhao, H., Heiss, G., Odden, M., Newman, A., Safford, M. 2018; 7 (12)

  Abstract

  There are no validated systems for characterizing long-term risk of severe sepsis in community-dwelling adults. We tested the ability of the REasons for Geographic and Racial Differences in Stroke-Severe Sepsis Risk Score (REGARDS-SSRS) to predict 10-year severe sepsis risk in separate cohorts of community-dwelling adults. We internally tested the REGARDS-SSRS on the REGARDS-Medicare subcohort. We then externally validated the REGARDS-SSRS using (1) the Cardiovascular Health Study (CHS) and (2) the Atherosclerosis Risk in Communities (ARIC) cohorts. Participants included community-dwelling adults: REGARDS-Medicare, age ≥65 years, n = 9522; CHS, age ≥65 years, n = 5888; ARIC, age 45⁻64 years, n = 11,584. The primary exposure was 10-year severe sepsis risk, predicted by the REGARDS-SSRS from participant sociodemographics, health behaviors, chronic medical conditions and select biomarkers. The primary outcome was first severe sepsis hospitalizations, defined as the concurrent presence of ICD-9 discharge diagnoses for a serious infection and organ dysfunction. Median SSRS in the cohorts were: REGARDS-Medicare 11 points (IQR 7⁻16), CHS 10 (IQR 6⁻15), ARIC 7 (IQR 5⁻10). Severe sepsis incidence rates were: REGARDS-Medicare 30.7 per 1000 person-years (95% CI: 29.2⁻32.2); CHS 11.9 (10.9⁻12.9); ARIC 6.8 (6.3⁻7.3). SSRS discrimination for first severe sepsis events were: REGARDS-Medicare C-statistic 0.704 (95% CI: 0.691⁻0.718), CHS 0.696 (0.675⁻0.716), ARIC 0.697 (0.677⁻0.716). The REGARDS-SRSS may potentially play a role in identifying community-dwelling adults at high severe sepsis risk.

  View details for PubMedID 30544923

• Potential Cardiovascular Disease Events Prevented with Adoption of the 2017 American College of Cardiology/American Heart Association Blood Pressure Guideline. Circulation Bress, A. P., Colantonio, L. D., Cooper, R., Kramer, H., Booth Iii, J. N., Odden, M. C., Bibbins-Domingo, K., Shimbo, D., Whelton, P. K., Levitan, E. B., Howard, G., Bellows, B. K., Kleindorfer, D., Safford, M. M., Muntner, P., Moran, A. E. 2018

  Abstract

  BACKGROUND: Over 10 years, achieving and maintaining 2017 ACC/AHA guideline goals could prevent 3.0 million (UR, 1.1-5.1 million), 0.5 million (UR, 0.2-0.7 million), and 1.4 million (UR, 0.6-2.0 million) cardiovascular disease (CVD) events compared with maintaining current blood pressure (BP) levels, achieving 2003 Seventh Joint National Committee Report goals, and achieving 2014 Eighth Joint National Committee goals, respectively. We estimated the number of cardiovascular disease events prevented and treatment-related serious adverse events incurred over 10 years among US adults with hypertension by achieving 2017 ACC/AHA guideline-recommended BP goals compared with (1) current BP levels, (2) achieving 2003 Seventh Joint National Committee Report BP goals, and (3) achieving 2014 Eighth Joint National Committee panel member report BP goals.METHODS: US adults aged ≥45 years with an indication for BP treatment were grouped according to recommendations for antihypertensive drug therapy in the 2017 ACC/AHA guideline, 2003 Seventh Joint National Committee Report, and 2014 Eighth Joint National Committee. Population sizes were estimated from the 2011 to 2014 National Health and Nutrition Examination Surveys. Rates for fatal and nonfatal CVD events (stroke, coronary heart disease, or heart failure) were estimated from the REGARDS (REasons for Geographic And Racial Differences in Stroke) study, weighted to the US population. CVD risk reductions with treatment to BP goals and risk for serious adverse events were obtained from meta-analyses of BP-lowering trials. CVD events prevented and treatment-related nonfatal serious adverse events over 10 years were calculated. Uncertainty surrounding main data inputs was expressed in uncertainty ranges (UR).RESULTS: Over ten years, achieving and maintaining 2017 ACC/AHA guideline goals compared with current BP levels, achieving 2003 Seventh Joint National Committee Report goals, or achieving 2014 Eighth Joint National Committee goals could prevent 3.0 million (UR, 1.1-5.1 million), 0.5 million (UR, 0.2-0.7 million), or 1.4 million (UR, 0.6-2.0 million) CVD events, respectively. Compared with current BP levels, achieving and maintaining 2017 goals could prevent 71.9 (UR, 26.6-122.3) CVD events per 1000 treated. Achieving 2017 guideline BP goals compared with current BP levels could also lead to nearly 3.3 million more serious adverse events over 10 years (UR, 2.2-4.4 million).CONCLUSIONS: Achieving and maintaining 2017 ACC/AHA BP goals could prevent a greater number of CVD events than achieving 2003 Seventh Joint National Committee Report or 2014 Eighth Joint National Committee BP goals but could also lead to more serious adverse events.

  View details for PubMedID 30586736

• Trajectories of Nonagenarian Health: Gender, Age, and Period Effects. American journal of epidemiology Odden, M. C., Koh, W. J., Arnold, A. M., Rawlings, A. M., Psaty, B. M., Newman, A. B. 2018

  Abstract

  The US population aged 90 years and older is growing rapidly and there are limited data on their health. The Cardiovascular Health Study is a prospective study of black and white adults ≥65 years recruited in two waves (1989-90 and 1992-93) from Medicare eligibility lists in Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Pittsburgh, Pennsylvania. We created a synthetic cohort of the 1,889 participants who had reached age 90 at baseline or during follow-up through July 16th, 2015. Participants entered the cohort at 90 years and we evaluated their changes in health after age 90 (median [IQR] follow-up: 3 [1.3-5] years). Measures of health included cardiovascular events, cognitive function, depressive symptoms, prescription medications, self-rated health, and measures of functional status. The mortality rate was high: 19.0 (95% CI: 17.8, 20.3) per 100 person-years in women and 20.9 (95% CI: 19.2, 22.8) in men. Cognitive function and all measures of functional status declined with age; these changes were similar by gender. When we isolated period effects, we found that medications use increased over time. These estimates can help inform future research and health care systems to meet the needs of this growing population.

  View details for PubMedID 30407481

• Formulating and Answering High-Impact Causal Questions in Physiologic Childbirth Science: Concepts and Assumptions JOURNAL OF MIDWIFERY & WOMENS HEALTH Snowden, J. M., Tilden, E. L., Odden, M. C. 2018; 63 (6): 721–30

  Abstract

  In this article, we conclude our 3-part series by focusing on several concepts that have proven useful for formulating causal questions and inferring causal effects. The process of causal inference is of key importance for physiologic childbirth science, so each concept is grounded in content related to women at low risk for perinatal complications. A prerequisite to causal inference is determining that the question of interest is causal rather than descriptive or predictive. Another critical step in defining a high-impact causal question is assessing the state of existing research for evidence of causality. We introduce 2 causal frameworks that are useful for this undertaking, Hill's causal considerations and the sufficient-component cause model. We then provide 3 steps to aid perinatal researchers in inferring causal effects in a given study. First, the researcher should formulate a rigorous and clear causal question. We introduce an example of epidural analgesia and labor progression to demonstrate this process, including the central role of temporality. Next, the researcher should assess the suitability of the given data set to answer this causal question. In randomized controlled trials, data are collected with the express purpose of answering the causal question. Investigators using observational data should also ensure that their chosen causal question is answerable with the available data. Finally, investigators should design an analysis plan that targets the causal question of interest. Some data structures (eg, time-dependent confounding by labor progress when estimating the effect of epidural analgesia on postpartum hemorrhage) require specific analytical tools to control for bias and estimate causal effects. The assumptions of consistency, exchangeability, and positivity may be especially useful in carrying out these steps. Drawing on appropriate causal concepts and considering relevant assumptions strengthens our confidence that research has reduced the likelihood of alternative explanations (eg bias, chance) and estimated a causal effect.

  View details for DOI 10.1111/jmwh.12868

  View details for Web of Science ID 000450030100011

  View details for PubMedID 29883521

• Serial circulating omega 3 polyunsaturated fatty acids and healthy ageing among older adults in the Cardiovascular Health Study: prospective cohort study BMJ-BRITISH MEDICAL JOURNAL Lai, H. M., Otto, M., Lemaitre, R. N., McKnight, B., Song, X., King, I. B., Chaves, P. M., Odden, M. C., Newman, A. B., Siscovick, D. S., Mozaffarian, D. 2018; 363: k4067

  Abstract

  To determine the longitudinal association between serial biomarker measures of circulating omega 3 polyunsaturated fatty acid (n3-PUFA) levels and healthy ageing.Prospective cohort study.Four communities in the United States (Cardiovascular Health Study) from 1992 to 2015.2622 adults with a mean (SD) age of 74.4 (4.8) and with successful healthy ageing at baseline in 1992-93.Cumulative levels of plasma phospholipid n3-PUFAs were measured using gas chromatography in 1992-93, 1998-99, and 2005-06, expressed as percentage of total fatty acids, including α-linolenic acid from plants and eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid from seafoood.Healthy ageing defined as survival without chronic diseases (ie, cardiovascular disease, cancer, lung disease, and severe chronic kidney disease), the absence of cognitive and physical dysfunction, or death from other causes not part of the healthy ageing outcome after age 65. Events were centrally adjudicated or determined from medical records and diagnostic tests.Higher levels of long chain n3-PUFAs were associated with an 18% lower risk (95% confidence interval 7% to 28%) of unhealthy ageing per interquintile range after multivariable adjustments with time-varying exposure and covariates. Individually, higher eicosapentaenoic acid and docosapentaenoic acid (but not docosahexaenoic acid) levels were associated with a lower risk: 15% (6% to 23%) and 16% (6% to 25%), respectively. α-linolenic acid from plants was not noticeably associated with unhealthy ageing (hazard ratio 0.92, 95% confidence interval 0.83 to 1.02).In older adults, a higher cumulative level of serially measured circulating n3-PUFAs from seafood (eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid), eicosapentaenoic acid, and docosapentaenoic acid (but not docosahexaenoic acid from seafood or α-linolenic acid from plants) was associated with a higher likelihood of healthy ageing. These findings support guidelines for increased dietary consumption of n3-PUFAs in older adults.

  View details for PubMedID 30333104

• Development, Construct Validity, and Predictive Validity of a Continuous Frailty Scale: Results From 2 Large US Cohorts AMERICAN JOURNAL OF EPIDEMIOLOGY Wu, C., Geldhof, G., Xue, Q., Kim, D. H., Newman, A. B., Odden, M. C. 2018; 187 (8): 1752–62

  Abstract

  Frailty is an age-related clinical syndrome of decreased resilience to stressors. Among numerous assessments of frailty, the frailty phenotype (FP) scale, proposed by Fried and colleagues has been the most widely used one. We aimed to develop a continuous frailty scale that may overcome limitations facing the categorical FP scale and to evaluate its construct validity, predictive validity, and measurement properties. Data were from the Cardiovascular Health Study (N = 4243) and Health and Retirement Study (N = 7600). Frailty was conceptualized as a continuous construct, measured by five measures used in FP scale: gait speed, grip strength, exhaustion, physical activity, and weight loss. We used confirmatory factor analysis to investigate the relationship between five indicators and the latent frailty construct. We examined the association of the continuous frailty scale with mortality and disability. The unidimensional model fit the data satisfactorily; similar factor structure was observed across two cohorts. Gait speed and weight loss were the strongest and weakest indicators, respectively; grip strength, exhaustion, and physical activity had similar strength in measuring frailty. In each cohort, the continuous frailty scale was strongly associated with mortality and disability and persisted to be associated with outcomes among robust and prefrail persons classified by the FP scale.

  View details for PubMedID 29688247

• Index of Healthy Aging in Chinese Older Adults: China Health and Retirement Longitudinal Study JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Wu, C., Newman, A. B., Dong, B., Odden, M. C. 2018; 66 (7): 1303–10

  Abstract

  To characterize the distribution of an index of healthy aging-the Chinese Healthy Aging Index (CHAI)-in Chinese adults aged 60 and older according to sociodemographic characteristics and geographic region and to examine the association between the CHAI and mortality, disability, and functional limitation over 4 years.Nationally representative cohort study.China Health and Retirement Longitudinal Study.Chinese adults aged 60 and older (N=3,740).Six CHAI components (systolic blood pressure, peak expiratory flow, Telephone Interview for Cognitive Status, estimated glomerular filtration rate, fasting glucose, C-reactive protein) were scored 0 (healthiest), 1, and 2 (unhealthiest) according to sex-specific tertiles or clinically relevant cut-points and summed to construct the CHAI (range 0-12).Mean CHAI score was 5.6; 5.7% had a score of 0 to 2 (healthiest), 23.0% a score of 3 or 4, 37.5% a score of 5 or 6, and 33.8% a score of 7 to 12 (unhealthiest). Participants who were younger, more educated, and married were much more likely to have an ideal CHAI profile (score 0-2). Age-adjusted prevalence of an ideal CHAI profile ranged from 1.7% in the south to 8.1% in the north. After multivariable adjustment, persons with a CHAI score of 3 to 12 had substantially higher odds of mortality, disability, and functional limitation than those with a score of 0 to 2. The CHAI further stratified outcomes for persons with no clinically recognizable comorbidities.Substantial variation exists in the CHAI according to sociodemographic characteristics and geographic regions. The CHAI could identify Chinese elderly adults with low risk of adverse outcomes and provide incremental value for risk prediction beyond clinically diagnosed comorbidities.

  View details for PubMedID 29684252

• Longitudinal Blood Pressure Changes and Kidney Function Decline in Persons Without Chronic Kidney Disease: Findings From the MESA Study AMERICAN JOURNAL OF HYPERTENSION Judson, G. L., Rubinsky, A. D., Shlipak, M. G., Katz, R., Kramer, H., Jacobs, D. R., Odden, M. C., Peralta, C. A. 2018; 31 (5): 600–608

  Abstract

  While changes in blood pressure (BP) are independently associated with cardiovascular events, less is known about the association between changes in BP and subsequent changes in renal function in adults with an estimated glomerular filtration rate (eGFR) of >60 ml/min/1.73 m2.The present study included 3,920 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) study who had ≥2 BP measurements during the first 5 years of MESA and had eGFR measurements at both year 5 and 10. Change in BP was estimated as the annualized slope of BP between year 0 and 5 based on linear mixed models (mean number of measurements = 4.0). Participants were then grouped into 1 of 3 categories based on the distribution of systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) change (top 20%, middle 21-79%, bottom 20%). We calculated eGFR from cystatin C (ml/min/1.73 m2), estimated annual change in eGFR (ml/min/1.73 m2/year), and defined rapid kidney function decline as a >30% decrease in eGFR from year 5 to 10. We used multivariable logistic regression adjusting for year 0 demographic and clinical characteristics, including eGFR and BP, to determine associations of BP change with rapid kidney function decline.Median age was 59 [interquartile range (IQR): 52, 67] and median eGFR at year 0 was 95.5 (IQR: 81.7, 105.9) ml/min/1.73 m2. Median SBP at year 0 was 111, 121, and 147 mm Hg for increasing, stable, and decreasing SBP change, respectively. Increasing SBP and widening PP change were each associated with higher odds of rapid kidney function decline compared with stable SBP and PP groups, respectively [odds ratio, OR 1.7 (95% confidence interval, CI 1.3, 2.4) for SBP; OR 1.4 (95% CI 1.1, 1.9) for PP]. Decreasing SBP was associated with rapid kidney function decline after adjusting for all covariates except for year 0 BP [OR 1.4 (95% CI 1.0, 1.8)], but this association was no longer statistically significant after adjustment for year 0 BP. There were no significant associations between DBP change and rapid decline in the fully adjusted models. Similar findings were seen with annual change in eGFR.Increasing SBP and widening PP over time were associated with greater risk for accelerated kidney function decline even at BP levels below established hypertension thresholds.

  View details for PubMedID 29036269

• Racial/ethnic heterogeneity in associations of blood pressure and incident cardiovascular disease by functional status in a prospective cohort: the Multi-Ethnic Study of Atherosclerosis BMJ OPEN Kaiser, P., Peralta, C. A., Kronmal, R., Shlipak, M. G., Psaty, B. M., Odden, M. C. 2018; 8 (2): e017746

  Abstract

  Research has demonstrated that the association between high blood pressure and outcomes is attenuated among older adults with functional limitations, compared with healthier elders. However, it is not known whether these patterns vary by racial/ethnic group. We evaluated race/ethnicity-specific patterns of effect modification in the association between blood pressure and incident cardiovascular disease (CVD) by functional status.We used data from the Multi-Ethnic Study of Atherosclerosis (2002-2004, with an average of 8.8 years of follow-up for incident CVD). We assessed effect modification of systolic blood pressure and cardiovascular outcomes by self-reported physical limitations and by age.The study included 6117 participants (aged 46 to 87; 40% white, 27% black, 22% Hispanic and 12% Chinese) who did not have CVD at the second study examination (when self-reported physical limitations were assessed).Incident CVD was defined as an incident myocardial infarction, coronary revascularisation, resuscitated cardiac arrest, angina, stroke (fatal or non-fatal) or death from CVD.We observed weaker associations between systolic blood pressure (SBP) and CVD among white adults with physical limitations (incident rate ratio (IRR) per 10 mm Hg higher SBP: 1.09 (95% CI 0.99 to 1.20)) than those without physical limitations (IRR 1.29 (1.19, 1.40); P value for interaction <0.01). We found a similar pattern among black adults. Poor precision among the estimates for Hispanic or Chinese participants limited the findings in these groups. The attenuated associations were consistent across both multiplicative and additive scales, though physical limitations showed clearer patterns than age on an additive scale.Attenuated associations between high blood pressure and incident CVD were observed for blacks and whites with poor function, though small sample sizes remain a limitation for identifying differences among Hispanic or Chinese participants. Identifying the characteristics that distinguish those in whom higher SBP is associated with less risk of morbidity or mortality may inform our understanding of the consequences of hypertension among older adults.

  View details for PubMedID 29476026

• Comparing methods to address bias in observational data: statin use and cardiovascular events in a US cohort INTERNATIONAL JOURNAL OF EPIDEMIOLOGY Kaiser, P., Arnold, A. M., Benkeser, D., Al Hazzouri, A., Hirsch, C. H., Psaty, B. M., Odden, M. C. 2018; 47 (1): 246–54

  Abstract

  The theoretical conditions under which causal estimates can be derived from observational data are challenging to achieve in the real world. Applied examples can help elucidate the practical limitations of methods to estimate randomized-controlled trial effects from observational data.We used six methods with varying design and analytic features to compare the 5-year risk of incident myocardial infarction among statin users and non-users, and used non-cardiovascular mortality as a negative control outcome. Design features included restriction to a statin-eligible population and new users only; analytic features included multivariable adjustment and propensity score matching.We used data from 5294 participants in the Cardiovascular Health Study from 1989 to 2004. For non-cardiovascular mortality, most methods produced protective estimates with confidence intervals that crossed the null. The hazard ratio (HR) was 0.92, 95% confidence interval: 0.58, 1.46 using propensity score matching among eligible new users. For myocardial infarction, all estimates were strongly protective; the propensity score-matched analysis among eligible new users resulted in a HR of 0.55 (0.29, 1.05)-a much stronger association than observed in randomized controlled trials.In designs that compare active treatment with non-treated participants to evaluate effectiveness, methods to address bias in observational data may be limited in real-world settings by residual bias.

  View details for PubMedID 29024975

• Age, Race, and Gender Factors in Incident Disability JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Jacob, M. E., Marron, M. M., Boudreau, R. M., Odden, M. C., Arnold, A. M., Newman, A. B. 2018; 73 (2): 194–97

  Abstract

  Incident disability rates enable the comparison of risk across populations. Understanding these by age, sex, and race is important for planning for the care of older adults and targeting prevention.We calculated incident disability rates among older adults in the Cardiovascular Health Study, a study of 5,888 older adults aged ≥ 65 years over 6 years of follow-up. Disability was defined in the following two ways: (i) self-report of disability (severe difficulty or inability) in any of six Activities of Daily Living (ADL), and (ii) mobility difficulty (any difficulty walking half a mile or climbing 10 steps). Incident disability rates were calculated as events per 100 person years for age, gender, and race groups.The incidence of ADL disability, and mobility difficulty were 2.7 (2.5-2.8), and 9.8 (9.4-10.3) events per 100 person years. Women, older participants, and blacks had higher rates in both domains.Incidence rates are considerably different based on the domain examined as well as age, race, and gender composition of the population. Prevention efforts should focus on high risk populations and attempt to ameliorate factors that increase risk in these groups.

  View details for PubMedID 29045556

• Outdoor air pollution and mosaic loss of chromosome Y in older men from the Cardiovascular Health Study. Environment international Wong, J. Y., Margolis, H. G., Machiela, M. n., Zhou, W. n., Odden, M. C., Psaty, B. M., Robbins, J. n., Jones, R. R., Rotter, J. I., Chanock, S. J., Rothman, N. n., Lan, Q. n., Lee, J. S. 2018; 116: 239–47

  Abstract

  Mosaic loss of chromosome Y (mLOY) can occur in a fraction of cells as men age, which is potentially linked to increased mortality risk. Smoking is related to mLOY; however, the contribution of air pollution is unclear.We investigated whether exposure to outdoor air pollution, age, and smoking were associated with mLOY.We analyzed baseline (1989-1993) blood samples from 933 men ≥65 years of age from the prospective Cardiovascular Health Study. Particulate matter ≤10 μm (PM10), carbon monoxide, nitrogen dioxide, sulfur dioxide, and ozone data were obtained from the U.S. EPA Aerometric Information Retrieval System for the year prior to baseline. Inverse-distance weighted air monitor data were used to estimate each participants' monthly residential exposure. mLOY was detected with standard methods using signal intensity (median log-R ratio (mLRR)) of the male-specific chromosome Y regions from Illumina array data. Linear regression models were used to evaluate relations between mean exposure in the prior year, age, smoking and continuous mLRR.Increased PM10 was associated with mLOY, namely decreased mLRR (p-trend = 0.03). Compared with the lowest tertile (≤28.5 μg/m3), the middle (28.5-31.0 μg/m3; β = -0.0044, p = 0.09) and highest (≥31 μg/m3; β = -0.0054, p = 0.04) tertiles had decreased mLRR, adjusted for age, clinic, race/cohort, smoking status and pack-years. Additionally, increasing age (β = -0.00035, p = 0.06) and smoking pack-years (β = -0.00011, p = 1.4E-3) were associated with decreased mLRR, adjusted for each other and race/cohort. No significant associations were found for other pollutants.PM10 may increase leukocyte mLOY, a marker of genomic instability. The sample size was modest and replication is warranted.

  View details for PubMedID 29698900

• Limited access to special education services for school-aged children with developmental delay RESEARCH IN DEVELOPMENTAL DISABILITIES Twardzik, E., Smit, E., Hatfield, B., Odden, M. C., Dixon-Ibarra, A., MacDonald, M. 2018; 72: 257–64

  Abstract

  Current policy in Oregon limits eligibility of children diagnosed with developmental delay for school-based services. Due to eligibility definitions, children with developmental delay may face additional barriers transitioning from early intervention/early childhood special education into school-based special education services.Examine the relationship between enrollment in school-based special education programs given a change in primary disability diagnosis.Logistic regression models were fit for children who enrolled in early intervention/early childhood special education services with a primary disability diagnosis of developmental delay and changed primary disability diagnosis before third grade (n=5076).Odds of enrollment in future special education were greater in children with a change in primary disability diagnosis after the age of five in comparison to children that had a change in primary disability diagnosis before the age of five, while adjusting for demographic characteristics (adjusted odds ratio: 2.37, 95% CI 1.92, 2.92).Results suggest that children who are diagnosed with a developmental delay and exit early childhood special education due to maximum age of eligibility are more likely to enroll in special education compared to children without a gap in service access.Gaps in service access during early development are associated with the need for supportive services later on in life.

  View details for PubMedID 29227958

• Prevalence and Correlates of Frailty Among Community-Dwelling Chinese Older Adults: The China Health and Retirement Longitudinal Study JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Wu, C., Smit, E., Xue, Q., Odden, M. C. 2018; 73 (1): 102–8

  Abstract

  Frailty is an age-related clinical syndrome of decreased resilience to stressors and is associated with numerous adverse outcomes. Although there is preponderance of literature on frailty in developed countries, limited investigations have been conducted in less developed regions including China-a country that has the world's largest aging population. We examined frailty prevalence in China by sociodemographics and geographic region, and investigated correlates of frailty.Participants were 5,301 adults aged ≥60 years from the China Health and Retirement Longitudinal Study. Frailty was identified by the validated physical frailty phenotype (PFP) scale. We estimated frailty prevalence in the overall sample and by sociodemographics. We identified age-adjusted frailty prevalence by geographical region. Bivariate associations of frailty with health and function measures were evaluated by chi-squared test and analysis of variance.We found 7.0% of adults aged 60 years or older were frail. Frailty is more prevalent at advanced ages, among women, and persons with low education. Age-adjusted frailty prevalence ranged from 3.3% in the Southeast and the Northeast to 9.1% in the Northwest, and was more than 1.5 times higher in rural versus urban areas. Frail versus nonfrail persons had higher prevalence of comorbidities, falls, disability, and functional limitation.We demonstrated the utility of the PFP scale in identifying frail Chinese elders, and found substantial sociodemographic and regional disparities in frailty prevalence. The PFP scale may be incorporated into clinical practice in China to identify the most vulnerable elders to reduce morbidity, prevent disability, and enable more efficient use of health care resources.

  View details for PubMedID 28525586

• Patterns of blood pressure response during intensive BP lowering and clinical events: results from the secondary prevention of small subcortical strokes trial BLOOD PRESSURE Ku, E., Scherzer, R., Odden, M. C., Shlipak, M., White, C. L., Field, T. S., Benavente, O., Pergola, P. E., Peralta, C. A. 2018; 27 (2): 73–81

  Abstract

  We applied cluster analysis to identify discrete patterns of concomitant responses of systolic (SBP), diastolic (DBP) and pulse pressure (PP) during intensive BP lowering; and to evaluate their clinical relevance and association with risk of mortality, major vascular events (MVEs), and stroke.We used an unsupervised cluster procedure to identify distinct patterns of BP change during the first 9 months of anti-hypertensive therapy intensification among 1,331 participants in the Secondary Prevention of Small Subcortical Strokes Trial who were previously randomized to lower BP target (SBP < 130 mm Hg) after lacunar stroke.The cluster procedure partitioned participants into three groups in the lower SBP target arm, persons with: 1) mildly elevated baseline SBP and minimal visit-to-visit BP variability (mild reducers); 2) moderately elevated baseline SBP and moderate visit-to-visit BP variability (moderate reducers); and 3) very elevated baseline SBP with very large visit-to-visit BP variability during intensification (large reducers). In the lower SBP target group, moderate reducers had a higher risk of death (adjusted HR 1.6 [95% CI 1.0-2.7]), MVE (adjusted HR 2.1 [95% CI 1.4-3.2]), and stroke (adjusted HR 2.6[95% CI 1.7-4.1]) compared to mild reducers. Large reducers had the highest risk of death (adjusted HR 2.3 [95% CI 1.2-4.4]), but risk of MVE (HR = 1.7 [95%CI 0.9-3.1]) and stroke (HR = 1.6 [95%CI: 0.8-3.5]) were not statistically significantly different compared to mild reducers.Among persons with prior lacunar stroke, baseline BP levels, and BP variability in the setting of intensive BP lowering can identify discrete groups of persons at higher risk of adverse outcomes.

  View details for PubMedID 28952798

• Association Between More Intensive vs Less Intensive Blood Pressure Lowering and Risk of Mortality in Chronic Kidney Disease Stages 3 to 5 A Systematic Review and Meta-analysis JAMA INTERNAL MEDICINE Malhotra, R., Hoang Anh Nguyen, Benavente, O., Mete, M., Howard, B. V., Mant, J., Odden, M. C., Peralta, C. A., Cheung, A. K., Nadkarni, G. N., Coleman, R. L., Holman, R. R., Zanchetti, A., Peters, R., Beckett, N., Staessen, J. A., Ix, J. H. 2017; 177 (10): 1498–1505

  Abstract

  Trials in patients with hypertension have demonstrated that intensive blood pressure (BP) lowering reduces the risk of cardiovascular disease and all-cause mortality but may increase the risk of chronic kidney disease (CKD) incidence and progression. Whether intensive BP lowering is associated with a mortality benefit in patients with prevalent CKD remains unknown.To conduct a systematic review and meta-analysis of randomized clinical trials (RCTs) to investigate if more intensive compared with less intensive BP control is associated with reduced mortality risk in persons with CKD stages 3 to 5.Ovid MEDLINE, Cochrane Library, EMBASE, PubMed, Science Citation Index, Google Scholar, and clinicaltrials.gov electronic databases.All RCTs were included that compared 2 defined BP targets (either active BP treatment vs placebo or no treatment, or intensive vs less intensive BP control) and enrolled adults (≥18 years) with CKD stages 3 to 5 (estimated glomerular filtration rate <60 mL/min/1.73 m2) exclusively or that included a CKD subgroup between January 1, 1950, and June 1, 2016.Two of us independently evaluated study quality and extracted characteristics and mortality events among persons with CKD within the intervention phase for each trial. When outcomes within the CKD group had not previously been published, trial investigators were contacted to request data within the CKD subset of their original trials.All-cause mortality during the active treatment phase of each trial.This study identified 30 RCTs that potentially met the inclusion criteria. The CKD subset mortality data were extracted in 18 trials, among which there were 1293 deaths in 15 924 participants with CKD. The mean (SD) baseline systolic BP (SBP) was 148 (16) mm Hg in both the more intensive and less intensive arms. The mean SBP dropped by 16 mm Hg to 132 mm Hg in the more intensive arm and by 8 mm Hg to 140 mm Hg in the less intensive arm. More intensive vs less intensive BP control resulted in 14.0% lower risk of all-cause mortality (odds ratio, 0.86; 95% CI, 0.76-0.97; P = .01), a finding that was without significant heterogeneity and appeared consistent across multiple subgroups.Randomization to more intensive BP control is associated with lower mortality risk among trial participants with hypertension and CKD. Further studies are required to define absolute BP targets for maximal benefit and minimal harm.

  View details for PubMedID 28873137

• A Modified Healthy Aging Index and Its Association with Mortality: The National Health and Nutrition Examination Survey, 1999-2002 JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Wu, C., Smit, E., Sanders, J. L., Newman, A. B., Odden, M. C. 2017; 72 (10): 1437–44

  Abstract

  Comorbidity indices that are based on clinically recognized disease do not capture the full spectrum of health. The Healthy Aging Index (HAI) was recently developed to describe a wider range of health and disease across multiple organ systems. We characterized the distribution of a modified HAI (mHAI) by sociodemographics in a representative sample of the U.S. population. We also examined the association of the mHAI with mortality across individuals with different levels of clinically recognizable comorbidities.Data are from the National Health and Nutrition Examination Survey (1999-2000, 2001-2002) on 2,451 adults aged 60 years or older. Five mHAI components (systolic blood pressure, Digit Symbol Substitution Test, cystatin C, glucose, and respiratory problems) were scored 0 (healthiest), 1, or 2 (unhealthiest) by sex-specific tertiles or clinically relevant cutoffs and summed to construct the mHAI.The mean mHAI score was 4.3; 20.6% had a score of 0-2. 33.2% had a score of 3-4, 31.0% had a score of 5-6, and 15.2% had a score of 7-10. Mean mHAI scores were lower in adults who were younger, non-Hispanic whites, more educated, and married/living with partner. After multivariate adjustment, per unit higher of the mHAI was associated with higher all-cause mortality (HR = 1.19, 95% CI = 1.11-1.27) and higher cardiovascular mortality (HR = 1.23, 95% CI = 1.11-1.35). Within each comorbidity category (0, 1, 2, 3, 4+), the mHAI was still widely distributed and further stratified mortality.Substantial variation exists in the mHAI across sociodemographic subgroups. The mHAI could provide incremental value for mortality risk prediction beyond clinically diagnosed chronic diseases among elders.

  View details for PubMedID 28329253

• Evaluating the Impact and Cost-Effectiveness of Statin Use Guidelines for Primary Prevention of Coronary Heart Disease and Stroke CIRCULATION Heller, D. J., Coxson, P. G., Penko, J., Pletcher, M. J., Goldman, L., Odden, M. C., Kazi, D. S., Bibbins-Domingo, K. 2017; 136 (12): 1087-+

  Abstract

  Statins are effective in the primary prevention of atherosclerotic cardiovascular disease. The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guideline expands recommended statin use, but its cost-effectiveness has not been compared with other guidelines.We used the Cardiovascular Disease Policy Model to estimate the cost-effectiveness of the ACC/AHA guideline relative to current use, Adult Treatment Panel III guidelines, and universal statin use in all men 45 to 74 years of age and women 55 to 74 years of age over a 10-year horizon from 2016 to 2025. Sensitivity analyses varied costs, risks, and benefits. Main outcomes were incremental cost-effectiveness ratios and numbers needed to treat for 10 years per quality-adjusted life-year gained.Each approach produces substantial benefits and net cost savings relative to the status quo. Full adherence to the Adult Treatment Panel III guideline would result in 8.8 million more statin users than the status quo, at a number needed to treat for 10 years per quality-adjusted life-year gained of 35. The ACC/AHA guideline would potentially result in up to 12.3 million more statin users than the Adult Treatment Panel III guideline, with a marginal number needed to treat for 10 years per quality-adjusted life-year gained of 68. Moderate-intensity statin use in all men 45 to 74 years of age and women 55 to 74 years of age would result in 28.9 million more statin users than the ACC/AHA guideline, with a marginal number needed to treat for 10 years per quality-adjusted life-year gained of 108. In all cases, benefits would be greater in men than women. Results vary moderately with different risk thresholds for instituting statins and statin toxicity estimates but depend greatly on the disutility caused by daily medication use (pill burden).At a population level, the ACC/AHA guideline for expanded statin use for primary prevention is projected to treat more people, to save more lives, and to cost less compared with Adult Treatment Panel III in both men and women. Whether individuals benefit from long-term statin use for primary prevention depends more on the disutility associated with pill burden than their degree of cardiovascular risk.

  View details for PubMedID 28687710

• Functional Status Modifies the Association of Blood Pressure with Death in Elders: Health and Retirement Study JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Wu, C., Smit, E., Peralta, C. A., Sarathy, H., Odden, M. C. 2017; 65 (7): 1482–89

  Abstract

  To examine whether grip strength, gait speed, and the combination of the two physical functioning measures modified the association of systolic BP (SBP) and diastolic BP (DBP) with mortality.Nationally representative cohort study.Health and Retirement Study.7,492 U.S. adults aged ≥65 years.Grip strength was measured by a hand dynamometer and classified as normal (≥16 kg for female; ≥26 kg for male) and weak. Gait speed was assessed over a 98.5-inch walk and classified as non-slow (≥0.60 m/s for female; ≥0.52 m/s for male) and slow.Over an average follow-up time of 6.0 years, 1,870 (25.0%) participants died. After adjustment for socio-demographic, behavioral, and clinical measures, elevated SBP (≥150 mmHg) and DBP (≥90 mmHg) was associated with a 24% (95% CI, 7-43%) and 25% (95% CI, 5-49%) higher mortality among participants with normal grip strength. In contrast, elevated SBP and DBP was associated with a 6% (95% CI, 31 to -27%) and a 16% (95% CI, 46 to -26%) lower mortality among those with weak grip strength (P-values of interactions: both=.07). The inverse relations between BP with death were most pronounced among slow walkers with weak grip strength. The HRs of elevated SBP and DBP for death was 0.85 (95% CI, 0.56-1.29) and 0.53 (95% CI, 0.30-0.96), respectively, and was substantially different from non-slow walkers with normal grip strength (HR = 1.24 and 1.15, respectively; P-values of interactions: both <.001). Therefore, associations of BP with death varied modestly by gait speed.Grip strength modified the association of BP with death. Combination of grip strength and gait speed has incremental value for modifying the association of BP with death.

  View details for PubMedID 28306145

• Factors Associated With Ischemic Stroke Survival and Recovery in Older Adults STROKE Winovich, D., Longstreth, W. T., Arnold, A. M., Varadhan, R., Al Hazzouri, A., Cushman, M., Newman, A. B., Odden, M. C. 2017; 48 (7): 1818-+

  Abstract

  Little is known about factors that predispose older adults to poor recovery after a stroke. In this study, we sought to evaluate prestroke measures of frailty and related factors as markers of vulnerability to poor outcomes after ischemic stroke.In participants aged 65 to 99 years with incident ischemic strokes from the Cardiovascular Health Study, we evaluated the association of several risk factors (frailty, frailty components, C-reactive protein, interleukin-6, and cystatin C) assessed before stroke with stroke outcomes of survival, cognitive decline (≥5 points on Modified Mini-Mental State Examination), and activities of daily living decline (increase in limitations).Among 717 participants with incident ischemic stroke with survival data, slow walking speed, low grip strength, and cystatin C were independently associated with shorter survival. Among participants <80 years of age, frailty and interleukin-6 were also associated with shorter survival. Among 509 participants with recovery data, slow walking speed, and low grip strength were associated with both cognitive and activities of daily living decline poststroke. C-reactive protein and interleukin-6 were associated with poststroke cognitive decline among men only. Frailty status was associated with activities of daily living decline among women only.Markers of physical function-walking speed and grip strength-were consistently associated with survival and recovery after ischemic stroke. Inflammation, kidney function, and frailty also seemed to be determinants of survival and recovery after an ischemic stroke. These markers of vulnerability may identify targets for differing pre and poststroke medical management and rehabilitation among older adults at risk of poor stroke outcomes.

  View details for PubMedID 28526765

• Association of Blood Pressure Trajectory With Mortality, Incident Cardiovascular Disease, and Heart Failure in the Cardiovascular Health Study AMERICAN JOURNAL OF HYPERTENSION Smitson, C. C., Scherzer, R., Shlipak, M. G., Psaty, B. M., Newman, A. B., Sarnak, M. J., Odden, M. C., Peralta, C. A. 2017; 30 (6): 587–93

  Abstract

  Common blood pressure (BP) trajectories are not well established in elderly persons, and their association with clinical outcomes is uncertain.We used hierarchical cluster analysis to identify discrete BP trajectories among 4,067 participants in the Cardiovascular Health Study using repeated BP measures from years 0 to 7. We then evaluated associations of each BP trajectory cluster with all-cause mortality, incident cardiovascular disease (CVD, defined as stroke or myocardial infarction) (N = 2,837), and incident congestive heart failure (HF) (N = 3,633) using Cox proportional hazard models.Median age was 77 years at year 7. Over a median 9.3 years of follow-up, there were 2,475 deaths, 659 CVD events, and 1,049 HF events. The cluster analysis identified 3 distinct trajectory groups. Participants in cluster 1 (N = 1,838) had increases in both systolic (SBP) and diastolic (DBP) BPs, whereas persons in cluster 2 (N = 1,109) had little change in SBP but declines in DBP. Persons in cluster 3 (N = 1,120) experienced declines in both SBP and DBP. After multivariable adjustment, clusters 2 and 3 were associated with increased mortality risk relative to cluster 1 (hazard ratio = 1.21, 95% confidence interval: 1.06-1.37 and hazard ratio = 1.20, 95% confidence interval: 1.05-1.36, respectively). Compared to cluster 1, cluster 3 had higher rates of incident CVD but associations were not statistically significant in demographic-adjusted models (hazard ratio = 1.16, 95% confidence interval: 0.96-1.39). Findings were similar when stratified by use of antihypertensive therapy.Among community-dwelling elders, distinct BP trajectories were identified by integrating both SBP and DBP. These clusters were found to have differential associations with outcomes.

  View details for PubMedID 28338937

• Perceived Walking Speed, Measured Tandem Walk, Incident Stroke, and Mortality in Older Latino Adults: A Prospective Cohort Study JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Al Hazzouri, A., Mayeda, E., Elfassy, T., Lee, A., Odden, M. C., Thekkethala, D., Wright, C. B., Glymour, M. M., Haan, M. N. 2017; 72 (5): 676–82

  Abstract

  Walking speed is associated with functional status and all-cause mortality. Yet the relationship between walking speed and stroke, also a leading cause of disability, remains poorly understood, especially in older Latino adults who suffer from a significant burden of stroke.A total of 1,486 stroke-free participants from the Sacramento Area Latino Study on Aging, aged 60 and older at baseline in 1998-1999, were followed annually through 2010. Participants reported their usual walking speed outdoors which was classified into slow, medium, or fast. We also assessed timed tandem walk ability (unable or eight or more errors vs less than eight errors). We ascertained three incident stroke endpoints: total stroke, nonfatal stroke, and fatal stroke. Using Cox proportional hazards models, we estimated hazard ratios (HRs) for stroke at different walking speed and timed tandem walk categories.Over an average of 6 years of follow-up (SD = 2.8), the incidence rate of total strokes was 23.2/1,000 person-years for slow walkers compared to 15.6/1,000 person-years for medium walkers, and 7.6/1,000 person-years for fast walkers. In Cox models adjusted for sociodemographics, cardiovascular risk, cognition and functional status, and self-rated health, the hazard of total stroke was 31% lower for medium walkers (HR: 0.69, 95% confidence interval [CI]: 0.47, 1.02) and 56% lower for fast walkers (HR: 0.44, 95% CI: 0.24, 0.82) compared with slow walkers. We found similar associations with timed tandem walk ability (fully adjusted HR: 0.66, 95% CI: 0.45, 0.98).Our findings suggest perceived walking speed captures more than self-rated health alone and is a strong risk factor for stroke risk in Latino older adults.

  View details for PubMedID 27549992

• Effect of Intensive Blood Pressure Control on Gait Speed and Mobility Limitation in Adults 75 Years or Older A Randomized Clinical Trial JAMA INTERNAL MEDICINE Odden, M. C., Peralta, C. A., Berlowitz, D. R., Johnson, K. C., Whittle, J., Kitzman, D. W., Beddhu, S., Nord, J. W., Papademetriou, V., Williamson, J. D., Pajewski, N. M., Systolic Blood Pressure 2017; 177 (4): 500–507

  Abstract

  Intensive blood pressure (BP) control confers a benefit on cardiovascular morbidity and mortality; whether it affects physical function outcomes is unknown.To examine the effect of intensive BP control on changes in gait speed and mobility status.This randomized, clinical trial included 2636 individuals 75 years or older with hypertension and no history of type 2 diabetes or stroke who participated in the Systolic Blood Pressure Intervention Trial (SPRINT). Data were collected from November 8, 2010, to December 1, 2015. Analysis was based on intention to treat.Participants were randomized to intensive treatment with a systolic BP target of less than 120 mm Hg (n = 1317) vs standard treatment with a BP target of less than 140 mm Hg (n = 1319).Gait speed was measured using a 4-m walk test. Self-reported information concerning mobility was obtained from items on the Veterans RAND 12-Item Health Survey and the EQ-5D. Mobility limitation was defined as a gait speed less than 0.6 meters per second (m/s) or self-reported limitations in walking and climbing stairs.Among the 2629 participants in whom mobility status could be defined (996 women [37.9%]; 1633 men [62.1%]; mean [SD] age, 79.9 [4.0] years), median (interquartile range) follow-up was 3 (2-3) years. No difference in mean gait speed decline was noted between the intensive- and standard-treatment groups (mean difference, 0.0004 m/s per year; 95% CI, -0.005 to 0.005; P = .88). No evidence of any treatment group differences in subgroups defined by age, sex, race or ethnicity, baseline systolic BP, chronic kidney disease, or a history of cardiovascular disease were found. A modest interaction was found for the Veterans RAND 12-Item Health Survey Physical Component Summary score, although the effect did not reach statistical significance in either subgroup, with mean differences of 0.004 (95% CI, -0.002 to 0.010) m/s per year among those with scores of at least 40 and -0.008 (95% CI, -0.016 to 0.001) m/s per year among those with scores less than 40 (P = .03 for interaction). Multistate models allowing for the competing risk of death demonstrated no effect of intensive treatment on transitions to mobility limitation (hazard ratio, 1.06; 95% CI, 0.92-1.22).Among adults 75 years or older in SPRINT, treating to a systolic BP target of less than 120 mm Hg compared with a target of less than 140 mm Hg had no effect on changes in gait speed and was not associated with changes in mobility limitation.clinicaltrials.gov Identifier: NCT01206062.

  View details for PubMedID 28166324

• Absolute Rates of Heart Failure, Coronary Heart Disease, and Stroke in Chronic Kidney Disease An Analysis of 3 Community-Based Cohort Studies JAMA CARDIOLOGY Bansal, N., Katz, R., Robinson-Cohen, C., Odden, M. C., Dalrymple, L., Shlipak, M. G., Sarnak, M. J., Siscovick, D. S., Zelnick, L., Psaty, B. M., Kestenbaum, B., Correa, A., Afkarian, M., Young, B., de Boer, I. H. 2017; 2 (3): 314–18

  Abstract

  Cardiovascular disease is the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). Understanding the relative contributions of cardiovascular disease event types to the excess burden of cardiovascular disease is important for developing effective strategies to improve outcomes.To determine absolute rates and risk differences of incident heart failure (HF), coronary heart disease (CHD), and stroke in participants with vs without CKD.We pooled participants without prevalent cardiovascular disease from 3 community-based cohort studies: the Jackson Heart Study, Cardiovascular Health Study, and Multi-Ethnic Study of Atherosclerosis. The Jackson Heart Study was conducted between 2000 and 2010, the Cardiovascular Health Study was conducted between 1989 and 2003, and the Multi-Ethnic Study of Atherosclerosis was conducted between 2000 and 2012.Chronic kidney disease was defined as estimated glomerular filtration rate less than 60 mL/min/1.73 m2, calculated using the combined creatinine-cystatin C CKD-Epidemiology Collaboration Equation.Poisson regression was used to calculate incidence rates (IRs) and risk differences of adjudicated incident HF, CHD, and stroke, comparing participants with vs without CKD.Among 14 462 participants, the mean (SD) age was 63 (12) years, 59% (n = 8533) were women, and 44% (n = 6363) were African American. Overall, 1461 (10%) had CKD (mean [SD] estimated glomerular filtration rate, 49 [10] mL/min/1.73 m2). Unadjusted IRs for participants with and without CKD, respectively, were 22.0 (95% CI, 19.3-24.8) and 6.2 (95% CI, 5.8-6.7) per 1000 person-years for HF; 24.5 (95% CI, 21.6-27.5) and 8.4 (95% CI, 7.9-9.0) per 1000 person-years for CHD; and 13.4 (95% CI, 11.3-15.5) and 4.8 (95% CI, 4.4-5.3) for stroke. Adjusting for demographics, cohort, hypertension, diabetes, hyperlipidemia, and tobacco use, risk differences comparing participants with vs without CKD (per 1000 person-years) were 2.3 (95% CI, 1.2-3.3) for HF, 2.3 (95% CI, 1.2-3.4) for CHD, and 0.8 (95% CI, 0.09-1.5) for stroke. Among African American and Hispanic participants, adjusted risk differences comparing participants with vs without CKD for HF were 3.5 (95% CI, 1.5-5.5) and 7.8 (95% CI, 2.2-13.3) per 1000 person-years, respectively.Among 3 diverse community-based cohorts, CKD was associated with an increased risk of HF that was similar in magnitude to CHD and greater than stroke. The excess risk of HF associated with CKD was particularly large among African American and Hispanic individuals. Efforts to improve health outcomes for patients with CKD should prioritize HF in addition to CHD prevention.

  View details for PubMedID 28002548

• Visit-to-Visit Blood Pressure Variability and Mortality and Cardiovascular Outcomes Among Older Adults: The Health, Aging, and Body Composition Study AMERICAN JOURNAL OF HYPERTENSION Wu, C., Shlipak, M. G., Stawski, R. S., Peralta, C. A., Psaty, B. M., Harris, T. B., Satterfield, S., Shiroma, E. J., Newman, A. B., Odden, M. C., Hlth ABC Study 2017; 30 (2): 151–58

  Abstract

  Level of blood pressure (BP) is strongly associated with cardiovascular (CV) events and mortality. However, it is questionable whether mean BP can fully capture BP-related vascular risk. Increasing attention has been given to the value of visit-to-visit BP variability.We examined the association of visit-to-visit BP variability with mortality, incident myocardial infarction (MI), and incident stroke among 1,877 well-functioning elders in the Health, Aging, and Body Composition Study. We defined visit-to-visit diastolic BP (DBP) and systolic BP (SBP) variability as the root-mean-square error of person-specific linear regression of BP as a function of time. Alternatively, we counted the number of considerable BP increases and decreases (separately; 10mm Hg for DBP and 20mm Hg for SBP) between consecutive visits for each individual.Over an average follow-up of 8.5 years, 623 deaths (207 from CV disease), 153 MIs, and 156 strokes occurred. The median visit-to-visit DBP and SBP variability was 4.96 mmHg and 8.53 mmHg, respectively. After multivariable adjustment, visit-to-visit DBP variability was related to higher all-cause (hazard ratio (HR) = 1.18 per 1 SD, 95% confidence interval (CI) = 1.01-1.37) and CV mortality (HR = 1.35, 95% CI = 1.05-1.73). Additionally, individuals having more considerable decreases of DBP (≥10mm Hg between 2 consecutive visits) had higher risk of all-cause (HR = 1.13, 95% CI = 0.99-1.28) and CV mortality (HR = 1.30, 95% CI = 1.05-1.61); considerable increases of SBP (≥20mm Hg) were associated with higher risk of all-cause (HR = 1.18, 95% CI = 1.03-1.36) and CV mortality (HR = 1.37, 95% CI = 1.08-1.74).Visit-to-visit DBP variability and considerable changes in DBP and SBP were risk factors for mortality in the elderly.

  View details for PubMedID 27600581

• Blood Pressure Trajectory, Gait Speed, and Outcomes: The Health, Aging, and Body Composition Study (vol 71, pg 1688, 2016) JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Odden, M. C., Wu, C., Shlipak, M. G., Psaty, B. M., Katz, R., Applegate, W. B., Harris, T., Newman, A. B., Peralta, C. A., Hlth ABC Study 2016; 71 (12): E1

  View details for PubMedID 27838648

• Blood Pressure Trajectory, Gait Speed, and Outcomes: The Health, Aging, and Body Composition Study JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Odden, M. C., Wu, C., Shlipak, M. G., Psaty, B. M., Katz, R., Applegate, W. B., Harris, T., Newman, A. B., Peralta, C. A., Hlth ABC Study 2016; 71 (12): 1688–94

  Abstract

  The present study aimed to (i) evaluate previous observations that the association of blood pressure (BP) with outcomes varies by gait speed and (ii) evaluate the association of subsequent changes in BP and cardiovascular risk.Participants included 2,669 adults aged 70-79 years in the Health, Aging, and Body Composition (Health ABC) study. Gait speed was dichotomized at ≥1.0 m/s over a 20-m test at baseline. BP was measured at baseline, and changes in BP over 5 years were evaluated using (i) population-based trajectory models and (ii) intraindividual mean and slope.Over a mean of 10 years, there were 1,366 deaths, 336 first myocardial infarctions, and 295 first strokes. There was a differential pattern of association between baseline systolic BP and diastolic BP and outcomes among brisk and moderate speed walkers. For example, the association between higher diastolic BP and mortality was in the protective direction for moderate speed walkers (hazard ratio = 0.75; 95% confidence interval: 0.63, 0.91) per 10 mmHg higher, whereas it was null in brisk walkers (hazard ratio = 1.05; 95% confidence interval: 0.98, 1.11), p value for interaction .01. The 5-year population-based trajectories did not add important information beyond baseline BP. Individual slopes in both systolic BP and diastolic BP did not appear to have important associations with the outcomes.In this study, we found that the overall level of BP was associated with myocardial infarction, stroke, and death, and this association differed by baseline gait speed, whereas changes in BP were not associated with these outcomes.

  View details for PubMedID 27142696

• Effectiveness of a Scaled-Up Arthritis Self-Management Program in Oregon: Walk With Ease AMERICAN JOURNAL OF PUBLIC HEALTH Conte, K. P., Odden, M. C., Linton, N. M., Harvey, S. 2016; 106 (12): 2227–30

  Abstract

  To evaluate the effectiveness of Walk With Ease (WWE), an evidence-based arthritis self-management program that was scaled up in Oregon in 2012 to 2014.Guided by the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework, we collected participant surveys and attendance records and conducted observations. Preprogram and postprogram, participants self-reported pain and fatigue (scale: 0-10 points; high scores indicate more pain and fatigue) and estimated episodes of physical activity per week in the last month.Recruitment successfully reached the targeted population-sedentary adults with arthritis (n = 598). Participants reported significant reduction in pain (-0.47 points; P = .006) and fatigue (-0.58 points; P = .021) and increased physical activity (0.86 days/week; P < .001). WWE was adopted by workplaces and medical, community, faith, and retirement centers. Most WWE programs were delivered with high fidelity; average attendance was 47%.WWE is suitable for implementation by diverse organizations. Effect sizes for pain and fatigue were less than those in the original WWE studies, but this is to be expected for a large-scale implementation. Public Health Implications. WWE can be effectively translated to diverse, real-world contexts to help sedentary adults increase physical activity and reduce pain and fatigue.

  View details for PubMedID 27736216

• Projected Impact of Mexico's Sugar-Sweetened Beverage Tax Policy on Diabetes and Cardiovascular Disease: A Modeling Study PLOS MEDICINE Maria Sanchez-Romero, L., Penko, J., Coxson, P. G., Fernandez, A., Mason, A., Moran, A. E., Avila-Burgos, L., Odden, M., Barquera, S., Bibbins-Domingo, K. 2016; 13 (11): e1002158

  Abstract

  Rates of diabetes in Mexico are among the highest worldwide. In 2014, Mexico instituted a nationwide tax on sugar-sweetened beverages (SSBs) in order to reduce the high level of SSB consumption, a preventable cause of diabetes and cardiovascular disease (CVD). We used an established computer simulation model of CVD and country-specific data on demographics, epidemiology, SSB consumption, and short-term changes in consumption following the SSB tax in order to project potential long-range health and economic impacts of SSB taxation in Mexico.We used the Cardiovascular Disease Policy Model-Mexico, a state transition model of Mexican adults aged 35-94 y, to project the potential future effects of reduced SSB intake on diabetes incidence, CVD events, direct diabetes healthcare costs, and mortality over 10 y. Model inputs included short-term changes in SSB consumption in response to taxation (price elasticity) and data from government and market research surveys and public healthcare institutions. Two main scenarios were modeled: a 10% reduction in SSB consumption (corresponding to the reduction observed after tax implementation) and a 20% reduction in SSB consumption (possible with increases in taxation levels and/or additional measures to curb consumption). Given uncertainty about the degree to which Mexicans will replace calories from SSBs with calories from other sources, we evaluated a range of values for calorie compensation. We projected that a 10% reduction in SSB consumption with 39% calorie compensation among Mexican adults would result in about 189,300 (95% uncertainty interval [UI] 155,400-218,100) fewer incident type 2 diabetes cases, 20,400 fewer incident strokes and myocardial infarctions, and 18,900 fewer deaths occurring from 2013 to 2022. This scenario predicts that the SSB tax could save Mexico 983 million international dollars (95% UI $769 million-$1,173 million). The largest relative and absolute reductions in diabetes and CVD events occurred in the youngest age group modeled (35-44 y). This study's strengths include the use of an established mathematical model of CVD and use of contemporary Mexican vital statistics, data from health surveys, healthcare costs, and SSB price elasticity estimates as well as probabilistic and deterministic sensitivity analyses to account for uncertainty. The limitations of the study include reliance on US-based studies for certain inputs where Mexico-specific data were lacking (specifically the associations between risk factors and CVD outcomes [from the Framingham Heart Study] and SSB calorie compensation assumptions), limited data on healthcare costs other than those related to diabetes, and lack of information on long-term SSB price elasticity that is specific to geographic and economic subgroups.Mexico's high diabetes prevalence represents a public health crisis. While the long-term impact of Mexico's SSB tax is not yet known, these projections, based on observed consumption reductions, suggest that Mexico's SSB tax may substantially decrease morbidity and mortality from diabetes and CVD while reducing healthcare costs.

  View details for PubMedID 27802278

• Association of retirement age with mortality: a population-based longitudinal study among older adults in the USA JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH Wu, C., Odden, M. C., Fisher, G. G., Stawski, R. S. 2016; 70 (9): 917–23

  Abstract

  Retirement is an important transitional process in later life. Despite a large body of research examining the impacts of health on retirement, questions still remain regarding the association of retirement age with survival. We aimed to examine the association between retirement age and mortality among healthy and unhealthy retirees and to investigate whether sociodemographic factors modified this association.On the basis of the Health and Retirement Study, 2956 participants who were working at baseline (1992) and completely retired during the follow-up period from 1992 to 2010 were included. Healthy retirees (n=1934) were defined as individuals who self-reported health was not an important reason to retire. The association of retirement age with all-cause mortality was analysed using the Cox model. Sociodemographic effect modifiers of the relation were examined.Over the study period, 234 healthy and 262 unhealthy retirees died. Among healthy retirees, a 1-year older age at retirement was associated with an 11% lower risk of all-cause mortality (95% CI 8% to 15%), independent of a wide range of sociodemographic, lifestyle and health confounders. Similarly, unhealthy retirees (n=1022) had a lower all-cause mortality risk when retiring later (HR 0.91, 95% CI 0.88 to 0.94). None of the sociodemographic factors were found to modify the association of retirement age with all-cause mortality.Early retirement may be a risk factor for mortality and prolonged working life may provide survival benefits among US adults.

  View details for PubMedID 27001669

• Gender Differences in the Combined Effects of Cardiovascular Disease and Osteoarthritis on Progression to Functional Impairment in Older Mexican Americans JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Haan, M. N., Lee, A., Odden, M. C., Aiello, A. E., To, T., Neuhaus, J. M. 2016; 71 (8): 1089–95

  Abstract

  Comorbidity (COM) is an important issue in aging. Cardiovascular disease (CVD) and osteoarthritis separately and together may modify the trajectories of functional decline. This analysis examines whether specific and unrelated COMs influence functional change differently and vary by gender.A cohort study of 1,789 (aged 60 years and older) Mexican Americans was followed annually for up to 10 years. We created four groups of COM (CVD alone, lower body osteoarthritis alone [OA], neither, or both). We employed mixed effects Poisson models with Instrumental Activities of Daily Living (IADL) as the outcome. We tested whether the association between COM and decline in functional status differed by gender.IADL impairments in those with CVD, OA, or both were significantly higher at baseline and increased more rapidly over time compared to those with neither condition. Compared to women with no COM, the number of IADL impairments in women with CVD alone were 1.36 times greater, with OA were 1.35 times greater, and both conditions were 1.26 times greater. Compared to men with no COM, IADL impairments in men with CVD alone were 1.15 times greater, OA alone were 1.12 times greater, and both were 1.26 times greater.Over time, the influence of COM on functional decline differs by specific combinations of COM and by gender. Aggregate COM scales obscure the biological and temporal heterogeneity in the effects of COM. Time-dependent-specific COMs better assess the development of impairment. Women experience a higher burden of functional impairment due to COM than men.

  View details for PubMedID 26893469

• Trajectories of function and biomarkers with age: the CHS All Stars Study INTERNATIONAL JOURNAL OF EPIDEMIOLOGY Newman, A. B., Sanders, J. L., Kizer, J. R., Boudreau, R. M., Odden, M. C., Al Hazzouri, A., Arnold, A. M. 2016; 45 (4): 1135–45

  Abstract

  Multimorbidity is a major driver of physical and cognitive impairment, but rates of decline are also related to ageing. We sought to determine trajectories of decline in a large cohort by disease status, and examined their correspondence with biomarkers of ageing processes including growth hormone, sex steroid, inflammation, visceral adiposity and kidney function pathways.We have followed the 5888 participants in the Cardiovascular Health Study (CHS) for healthy ageing and longevity since 1989-90. Gait speed, grip strength, modified mini-mental status examination (3MSE) and the digit symbol substitution test (DSST) were assessed annually to 1998-99 and again in 2005-06. Insulin-like growth hormone (IGF-1), dehydroepiandrosterone sulphate (DHEAS), interleukin-6 (IL-6), adiponectin and cystatin-C were assessed 3-5 times from stored samples. Health status was updated annually and dichotomized as healthy vs not healthy. Trajectories for each function measure and biomarker were estimated using generalized estimating equations as a function of age and health status using standardized values.Trajectories of functional decline showed strong age acceleration late in life in healthy older men and women as well as in chronically ill older adults. Adiponectin, IL-6 and cystatin-C tracked with functional decline in all domains; cystatin-C was consistently associated with functional declines independent of other biomarkers. DHEAS was independently associated with grip strength and IL-6 with grip strength and gait speed trajectories.Functional decline in late life appears to mark a fundamental ageing process in that it occurred and was accelerated in late life regardless of health status. Cystatin C was most consistently associated with these functional declines.

  View details for PubMedID 27272182

• Response by Peralta et al to Letter Regarding Article, "Effect of Intensive Versus Usual Blood Pressure Control on Kidney Function Among Individuals With Prior Lacunar Stroke: A Post Hoc Analysis of the Secondary Prevention of Small Subcortical Strokes (SPS3) Randomized Trial" CIRCULATION Peralta, C. A., McClure, L. A., Scherzer, R., Odden, M. C., White, C. L., Shlipak, M., Benavente, O., Pergola, P. E. 2016; 134 (4): E26–E27

  View details for PubMedID 27462061

• Responses to Financial Loss During the Great Recession: An Examination of Sense of Control in Late Midlife JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES Mejia, S. T., Settersten, R. A., Odden, M. C., Hooker, K. 2016; 71 (4): 734–44

  Abstract

  The "Great Recession" shocked the primary institutions that help individuals and families meet their needs and plan for the future. This study examines middle-aged adults' experiences of financial loss and considers how socioeconomic and interpersonal resources facilitate or hinder maintaining a sense of control in the face of economic uncertainty.Using the 2006 and 2010 waves of the Health and Retirement Study, change in income and wealth, giving help to and receiving help from others, household complexity, and sense of control were measured among middle-aged adults (n = 3,850; age = 51-60 years).Socioeconomic resources predicted both the level of and change in the engagement of interpersonal resources prior to and during the Great Recession. Experiences of financial loss were associated with increased engagement of interpersonal resources and decreased sense of control. The effect of financial loss was dampened by education. Sense of control increased with giving help and decreased with household complexity.Findings suggest that, across socioeconomic strata, proportional loss in financial resources resulted in a loss in sense of control. However, responses to financial loss differed by socioeconomic status, which differentiated the ability to maintain a sense of control following financial loss.

  View details for PubMedID 26307482

• Functional Status and Antihypertensive Therapy in Older Adults: A New Perspective on Old Data AMERICAN JOURNAL OF HYPERTENSION Charlesworth, C. J., Peralta, C. A., Odden, M. C. 2016; 29 (6): 690–95

  Abstract

  Functional status may be useful for identifying older adults who benefit from lower blood pressure. We examined whether functional status modifies the effect of antihypertensive treatment among older adults.Post hoc analyses of the Systolic Hypertension in the Elderly Program (SHEP), a randomized trial of antihypertensive therapy vs. placebo (1985-1991) in 4,736 adults aged 60 years or older with isolated systolic hypertension. Outcomes were all-cause death, cardiovascular (CV) death, myocardial infarction (MI), stroke, falls, and symptoms of hypotension. The effect modifier of interest was functional status, assessed by self-reported physical ability limitation (PAL).Among persons with no PAL, those receiving treatment had a lower rate of death, CV death, and MI compared with placebo (4.0, 2.9, and 4.2 per 1,000 person-years lower, respectively). In contrast, among persons with a PAL, those receiving treatment had a higher rate of death, CV death, and MI compared with placebo (8.6, 5.3, and 2.7 per 1,000 person-years higher, respectively). These patterns persisted in Cox models, although interaction terms did not reach statistical significance. Treatment remained protective for stroke regardless of functional status. The rate of falls associated with treatment differed by functional status; incidence-rate ratio = 0.81, 95% confidence interval (CI) = (0.66, 0.99), and 1.32, 95% CI = (0.87, 2.00) in participants without and with a PAL, respectively, in models adjusted for demographics and baseline blood pressure (P-value for interaction, 0.04).Functional status may modify the effect of antihypertensive treatment on MI, mortality, and falls, but not stroke, in older adults. Functional status should be examined in other trial settings.

  View details for PubMedID 26541570

• Gait Speed as a Guide for Blood Pressure Targets in Older Adults: A Modeling Study JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Odden, M. C., Moran, A. E., Coxson, P. G., Peralta, C. A., Goldman, L., Bibbins-Domingo, K. 2016; 64 (5): 1015–23

  Abstract

  To evaluate the potential for gait speed to inform decisions regarding optimal systolic blood pressure targets in older adults.Forecasting study from 2014 to 2023 using the Cardiovascular Disease Policy Model, a Markov model.National Health and Nutrition Examination Survey.U.S. adults aged 60-94 stratified into fast walking, slow walking, and poor functioning (noncompleters) based on measured gait speed.Lowering SBP to a target of 140 or 150 mmHg was modeled in persons with (secondary prevention) and without (primary prevention) a history of coronary heart disease or stroke. Based on clinical trials and observational studies, it was projected that slow-walking and poor-functioning participants would have greater noncardiovascular mortality. Myocardial infarctions (MIs), strokes, deaths, cost, and disability-adjusted life years (DALYs) were measured.Regardless of gait speed, it was projected that secondary prevention to a systolic blood pressure (SBP) of 140 mmHg would prevent more events and save more money than secondary prevention to 150 mmHg. Similarly, primary prevention to 140 mmHg in fast-walking adults was projected to prevent events and save money. In slow-walking adults, primary prevention to 150 mmHg was projected to prevent MIs and strokes and save DALYs but was cost saving only in men; intensification to 140 mmHg is of uncertain benefit in slow-walking individuals. Primary prevention in poor-functioning adults to a target of 140 or 150 mmHg SBP is projected to decrease DALYs.The most cost-effective SBP target varies according to history of cardiovascular disease and gait speed in persons aged 60-94. These projections highlight the need for better estimates of the benefits and harms of antihypertensive medications in a diverse group of older adults, because the net benefit is sensitive to the characteristics of the population treated.

  View details for PubMedID 27225357

• Incident Atrial Fibrillation and Disability-Free Survival in the Cardiovascular Health Study JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Wallace, E. R., Siscovick, D. S., Sitlani, C. M., Dublin, S., Mitchell, P. H., Odden, M. C., Hirsch, C. H., Thielke, S., Heckbert, S. R. 2016; 64 (4): 838–43

  Abstract

  To assess the associations between incident atrial fibrillation (AF) and disability-free survival and risk of disability.Prospective cohort study.Cardiovascular Health Study.Individuals aged 65 and older and enrolled in fee-for-service Medicare followed between 1991 and 2009 (MN = 4,046). Individuals with prevalent AF, activity of daily living (ADL) disability, or a history of stroke or heart failure at baseline were excluded.Incident AF was identified according to annual study electrocardiogram, hospital discharge diagnosis, or Medicare claims. Disability-free survival was defined as survival free of ADL disability (any difficulty or inability in bathing, dressing, eating, using the toilet, walking around the home, or getting out of a bed or chair). ADLs were assessed at annual study visits or in a telephone interview. Association between incident AF and disability-free survival or risk of disability was estimated using Cox proportional hazards models.Over an average of 7.0 years of follow-up, 660 individuals (16.3%) developed incident AF, and 3,112 (77%) became disabled or died. Incident AF was associated with shorter disability-free survival (hazard ratio (HR) for death or ADL disability = 1.71, 95% confidence interval (CI) = 1.55-1.90) and a higher risk of ADL disability (HR = 1.36, 95% CI = 1.18-1.58) than in individuals with no history of AF. This association persisted after adjustment for interim stroke and heart failure.These results suggest that AF is a risk factor for shorter functional longevity in older adults, independent of other risk factors and comorbid conditions.

  View details for PubMedID 26926559

• Effect of Intensive Versus Usual Blood Pressure Control on Kidney Function Among Individuals With Prior Lacunar Stroke A Post Hoc Analysis of the Secondary Prevention of Small Subcortical Strokes (SPS3) Randomized Trial CIRCULATION Peralta, C. A., McClure, L. A., Scherzer, R., Odden, M. C., White, C. L., Shlipak, M., Benavente, O., Pergola, P. 2016; 133 (6): 584–91

  Abstract

  The effect of intensive blood pressure (BP) lowering on kidney function among individuals with established cerebrovascular disease and preserved estimated glomerular filtration rate (eGFR) is not established.Among 2610 participants randomized to a lower (<130 mm Hg) versus higher (130-149 mm Hg) systolic BP target with repeated measures of serum creatinine, we evaluated differences by study arm in annualized eGFR decline and rapid decline (eGFR decline >30%) using linear mixed models and logistic regression, respectively. We assessed associations of both treatment and kidney function decline with stroke, major vascular events, and the composite of stroke, death, major vascular events, or myocardial infarction using multivariable Cox regression, separately and jointly including a test for interaction. Analyses were conducted by treatment arm. Mean age was 63±11 years; 949 participants (36%) were diabetic; and mean eGFR was 80±19 mL·min(-1)·1.73 m(-2). At 9 months, achieved systolic BP was 137±15 versus 127±14 mm Hg in the higher versus lower BP group, and differences were maintained throughout follow-up (mean, 3.2 years). Compared with the higher target, the lower BP target had a -0.50-mL·min(-1)·1.73 m(-2) per year (95% confidence interval [CI], -0.79 to -0.21) faster eGFR decline. Differences were most pronounced during the first year (-2.1 mL·min(-1)·1.73 m(-2); 95% CI, -0.97 to -3.2), whereas rates of eGFR decline did not differ after year 1 (-0.095; 95% CI, -0.47 to 0.23). A total of 313 patients (24%) in the lower BP group had rapid kidney function decline compared with 247 (19%) in the higher BP group (odds ratio, 1.4; 95% CI, 1.1-1.6). Differences in rapid decline by treatment arm were apparent in the first year (odds ratio, 1.4; 95% CI, 1.1-1.8) but were not significant after year 1 (odds ratio, 1.0; 95% CI, 0.73-1.4). Rapid decline was associated with higher risk for stroke, major vascular events, and composite after full adjustment among individuals randomized to the higher BP target (stroke hazard ratio, 1.93; 95% CI, 1.15-3.21) but not the lower BP arm (stroke hazard ratio, 0.93; 95% CI, 0.50-1.75; all P for interaction <0.06).In patients with prior lacunar stroke and relatively preserved kidney function, intensive BP lowering was associated with a greater likelihood of rapid kidney function decline. Differences were observed primarily during the first year of antihypertensive treatment. Rapid kidney function decline was not associated with increased risk for clinical events among those undergoing intensive BP lowering.URL: http://www.clinicalTrials.gov. Unique identifier: NCT00059306.

  View details for PubMedID 26762524

• Achieved Blood Pressure and Outcomes in the Secondary Prevention of Small Subcortical Strokes Trial HYPERTENSION Odden, M. C., McClure, L. A., Sawaya, B., White, C. L., Peralta, C. A., Field, T. S., Hart, R. G., Benavente, O. R., Pergola, P. E. 2016; 67 (1): 63–69

  Abstract

  Studies suggest a J-shaped association between blood pressure and cardiovascular events in the setting of intensive systolic blood pressure control; whether there is a similar association with stroke remains less well established. The Secondary Prevention of Small Subcortical Strokes was a randomized trial to evaluate higher (130-149 mm Hg) versus lower (<130 mm Hg) systolic blood pressure targets in participants with recent lacunar infarcts. We evaluated the association of mean achieved blood pressure, 6 months after randomization, and recurrent stroke, major vascular events, and all-cause mortality. After a mean follow up of 3.7 years, there was a J-shaped association between achieved blood pressure and outcomes; the lowest risk was at ≈124 and 67 mm Hg systolic and diastolic blood pressure, respectively. For example, above a systolic blood pressure of 124 mm Hg, 1 standard deviation higher (11.1 mm Hg) was associated with increased mortality (adjusted hazard ratio: 1.9; 95% confidence interval: 1.4, 2.7), whereas below this level, this relationship was inverted (0.29; 0.10, 0.79), P<0.001 for interaction. Above a diastolic blood pressure of 67 mm Hg, a 1 standard deviation higher (8.2 mm Hg) was associated with an increased risk of stroke (2.2; 1.4, 3.6), whereas below this level, the association was in the opposite direction (0.34; 0.13, 0.89), P=0.02 for interaction. The lowest risk of all events occurred at a nadir of ≈120 to 128 mm Hg systolic blood pressure and 65 to 70 mm Hg diastolic blood pressure. Future studies should evaluate the impact of excessive blood pressure reduction, especially in older populations with preexisting vascular disease.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059306.

  View details for PubMedID 26553236

• Microvascular and Macrovascular Abnormalities and Cognitive and Physical Function in Older Adults: Cardiovascular Health Study JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Kim, D., Grodstein, F., Newman, A. B., Chaves, P. M., Odden, M. C., Klein, R., Sarnak, M. J., Lipsitz, L. A. 2015; 63 (9): 1886–93

  Abstract

  To evaluate and compare the associations between microvascular and macrovascular abnormalities and cognitive and physical functionCross-sectional analysis of the Cardiovascular Health Study (1998-1999).Community.Individuals with available data on three or more of five microvascular abnormalities (brain, retina, kidney) and three or more of six macrovascular abnormalities (brain, carotid artery, heart, peripheral artery) (N = 2,452; mean age 79.5).Standardized composite scores derived from three cognitive tests (Modified Mini-Mental State Examination, Digit-Symbol Substitution Test, Trail-Making Test (TMT)) and three physical tests (gait speed, grip strength, 5-time sit to stand)Participants with high microvascular and macrovascular burden had worse cognitive (mean score difference = -0.30, 95% confidence interval (CI) = -0.37 to -0.24) and physical (mean score difference = -0.32, 95% CI = -0.38 to -0.26) function than those with low microvascular and macrovascular burden. Individuals with high microvascular burden alone had similarly lower scores than those with high macrovascular burden alone (cognitive function: -0.16, 95% CI = -0.24 to -0.08 vs -0.13, 95% CI = -0.20 to -0.06; physical function: -0.15, 95% CI = -0.22 to -0.08 vs -0.12, 95% CI = -0.18 to -0.06). Psychomotor speed and working memory, assessed using the TMT, were only impaired in the presence of high microvascular burden. Of the 11 vascular abnormalities considered, white matter hyperintensity, cystatin C-based glomerular filtration rate, large brain infarct, and ankle-arm index were independently associated with cognitive and physical function.Microvascular and macrovascular abnormalities assessed using noninvasive tests of the brain, kidney, and peripheral artery were independently associated with poor cognitive and physical function in older adults. Future research should evaluate the usefulness of these tests in prognostication.

  View details for PubMedID 26338279

• Polypharmacy Among Adults Aged 65 Years and Older in the United States: 1988-2010 JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Charlesworth, C. J., Smit, E., Lee, D. H., Alramadhan, F., Odden, M. C. 2015; 70 (8): 989–95

  Abstract

  Older adults frequently have several chronic health conditions which require multiple medications. We illustrated trends in prescription medication use over 20 years in the United States, and described characteristics of older adults using multiple medications in 2009-2010.Participants included 13,869 adults aged 65 years and older in the National Health & Nutrition Examination Survey (1988-2010). Prescription medication use was verified by medication containers. Potentially inappropriate medications were defined by the 2003 Beers Criteria.Between 1988 and 2010 the median number of prescription medications used among adults aged 65 and older doubled from 2 to 4, and the proportion taking ≥5 medications tripled from 12.8% (95% confidence interval: 11.1, 14.8) to 39.0% (35.8, 42.3).These increases were driven, in part, by rising use of cardioprotective and antidepressant medications. Use of potentially inappropriate medications decreased from 28.2% (25.5, 31.0) to 15.1% (13.2, 17.3) between 1988 and 2010. Higher medication use was associated with higher prevalence of functional limitation, activities of daily living limitation, and confusion/memory problems in 2009-2010, although these associations did not remain after adjustment for covariates. In multivariable models, older age, number of chronic conditions, and annual health care visits were associated with increased odds of using both 1-4 and ≥5 medications. Additionally, body mass index, higher income-poverty ratio, former smoking, and non-black non-white race were associated with use of ≥5 medications.Prescription medication use increased dramatically among older adults between 1988 and 2010. Contemporary older adults on multiple medications have worse health status compared with those on less medications, and appear to be a vulnerable population.

  View details for PubMedID 25733718

• Blood Pressure in Older Adults: the Importance of Frailty CURRENT HYPERTENSION REPORTS Odden, M. C., Beilby, P. R., Peralta, C. A. 2015; 17 (7): 55

  Abstract

  The importance of high blood pressure (BP) and the effect of BP lowering in older adults remain controversial due to the mixed evidence in this population. Frailty status may resolve the apparently conflicting findings and identify subpopulations who share common risk. Emerging evidence demonstrates that low BP is associated with poor outcomes in older frail adults or those with poor functional status. In contrast, in non-frail older adults, low BP appears beneficial. Frail older adults may be at increased risk of hypotension, serious fall injuries, and polypharmacy. Additionally, peripheral BP may not be the best prognostic measure in this population. The majority of clinical practice guidelines give little recommendation for frail older adults, which is likely due to their systematic underrepresentation in randomized controlled trials. Future studies need to consider modifications to safely include frail older adults, and guidelines should consider inclusion of evidence beyond randomized controlled trials.

  View details for PubMedID 26068656

• Cost-Effectiveness of Hypertension Therapy According to 2014 Guidelines NEW ENGLAND JOURNAL OF MEDICINE Moran, A. E., Odden, M. C., Thanataveerat, A., Tzong, K. Y., Rasmussen, P. W., Guzman, D., Williams, L., Bibbins-Domingo, K., Coxson, P. G., Goldman, L. 2015; 372 (17): 1677

  View details for Web of Science ID 000353294000028

  View details for PubMedID 25901443

• Cost-Effectiveness and Population Impact of Statins for Primary Prevention in Adults Aged 75 Years or Older in the United States ANNALS OF INTERNAL MEDICINE Odden, M. C., Pletcher, M. J., Coxson, P. G., Thekkethala, D., Guzman, D., Heller, D., Goldman, L., Bibbins-Domingo, K. 2015; 162 (8): 533-+

  Abstract

  Evidence to guide primary prevention in adults aged 75 years or older is limited.To project the population impact and cost-effectiveness of statin therapy in adults aged 75 years or older.Forecasting study using the Cardiovascular Disease Policy Model, a Markov model.Trial, cohort, and nationally representative data sources.U.S. adults aged 75 to 94 years.10 years.Health care system.Statins for primary prevention based on low-density lipoprotein cholesterol threshold of 4.91 mmol/L (190 mg/dL), 4.14 mmol/L (160 mg/dL), or 3.36 mmol/L (130 mg/dL); presence of diabetes; or 10-year risk score of at least 7.5%.Myocardial infarction (MI), coronary heart disease (CHD) death, disability-adjusted life-years, and costs.All adults aged 75 years or older in the National Health and Nutrition Examination Survey have a 10-year risk score greater than 7.5%. If statins had no effect on functional limitation or cognitive impairment, all primary prevention strategies would prevent MIs and CHD deaths and be cost-effective. Treatment of all adults aged 75 to 94 years would result in 8 million additional users and prevent 105 000 (4.3%) incident MIs and 68 000 (2.3%) CHD deaths at an incremental cost per disability-adjusted life-year of $25 200.An increased relative risk for functional limitation or mild cognitive impairment of 1.10 to 1.29 could offset the cardiovascular benefits.Limited trial evidence targeting primary prevention in adults aged 75 years or older.At effectiveness similar to that in trials, statins are projected to be cost-effective for primary prevention; however, even a small increase in geriatric-specific adverse effects could offset the cardiovascular benefit. Improved data on the potential benefits and harms of statins are needed to inform decision making.American Heart Association Western States Affiliate, National Institute on Aging, and the National Institute for Diabetes on Digestive and Kidney Diseases.

  View details for DOI 10.7326/M14-1430

  View details for Web of Science ID 000353244300013

  View details for PubMedID 25894023

  View details for PubMedCentralID PMC4476404

• Years of Able Life in Older Persons-The Role of Cardiovascular Imaging and Biomarkers: The Cardiovascular Health Study JOURNAL OF THE AMERICAN HEART ASSOCIATION Alshawabkeh, L. I., Yee, L. M., Gardin, J. M., Gottdiener, J. S., Odden, M. C., Bartz, T. M., Arnold, A. M., Mukamal, K. J., Wallace, R. B. 2015; 4 (4)

  Abstract

  As the U.S. population grows older, there is greater need to examine physical independence. Previous studies have assessed risk factors in relation to either disability or mortality, but an outcome that combines both is still needed.The Cardiovascular Health Study is a population-based, prospective study where participants underwent baseline echocardiogram, measurement of carotid intima-media thickness (IMT), and various biomarkers, then followed for up to 18 years. Years of able life (YAL) constituted the number of years the participant was able to perform all activities of daily living. Linear regression was used to model the relationship between selected measures and outcomes, adjusted for confounding variables. Among 4902 participants, mean age was 72.6 ± 5.4 years, median YAL for males was 8.8 (interquartile range [IQR], 4.3 to 13.8) and 10.3 (IQR, 5.8 to 15.8) for females. Reductions in YAL in the fully adjusted model for females and males, respectively, were: -1.34 (95% confidence interval [CI], -2.18, -0.49) and -1.41 (95% CI, -2.03, -0.8) for abnormal left ventricular (LV) ejection fraction, -0.5 (95% CI, -0.78, -0.22) and -0.62 (95% CI, -0.87, -0.36) per SD increase in LV mass, -0.5 (95% CI, -0.7, -0.29) and -0.79 (95% CI, -0.99, -0.58) for IMT, -0.5 (95% CI, -0.64, -0.37) and -0.79 (95% CI, -0.94, -0.65) for N-terminal pro-brain natriuretic peptide, -1.08 (95% CI, -1.34, -0.83) and -0.73 (95% CI, -0.97, -0.5) for high-sensitivity troponin-T, and -0.26 (95% CI, -0.42, -0.09) and -0.23 (95% CI, -0.41, -0.05) for procollagen-III N-terminal propeptide. Most tested variables remained significant even after adjusting for incident cardiovascular (CV) disease.In this population-based cohort, variables obtained by CV imaging and biomarkers of inflammation, coagulation, atherosclerosis, myocardial injury and stress, and cardiac collagen turnover were associated with YAL, an important outcome that integrates physical ability and longevity in older persons.

  View details for PubMedID 25907126

• Cost-Effectiveness of Hypertension Therapy According to 2014 Guidelines NEW ENGLAND JOURNAL OF MEDICINE Moran, A. E., Odden, M. C., Thanataveerat, A., Tzong, K. Y., Rasmussen, P. W., Guzman, D., Williams, L., Bibbins-Domingo, K., Coxson, P. G., Goldman, L. 2015; 372 (5): 447–55

  Abstract

  On the basis of the 2014 guidelines for hypertension therapy in the United States, many eligible adults remain untreated. We projected the cost-effectiveness of treating hypertension in U.S. adults according to the 2014 guidelines.We used the Cardiovascular Disease Policy Model to simulate drug-treatment and monitoring costs, costs averted for the treatment of cardiovascular disease, and quality-adjusted life-years (QALYs) gained by treating previously untreated adults between the ages of 35 and 74 years from 2014 through 2024. We assessed cost-effectiveness according to age, hypertension level, and the presence or absence of chronic kidney disease or diabetes.The full implementation of the new hypertension guidelines would result in approximately 56,000 fewer cardiovascular events and 13,000 fewer deaths from cardiovascular causes annually, which would result in overall cost savings. The projections showed that the treatment of patients with existing cardiovascular disease or stage 2 hypertension would save lives and costs for men between the ages of 35 and 74 years and for women between the ages of 45 and 74 years. The treatment of men or women with existing cardiovascular disease or men with stage 2 hypertension but without cardiovascular disease would remain cost-saving even if strategies to increase medication adherence doubled treatment costs. The treatment of stage 1 hypertension was cost-effective (defined as <$50,000 per QALY) for all men and for women between the ages of 45 and 74 years, whereas treating women between the ages of 35 and 44 years with stage 1 hypertension but without cardiovascular disease had intermediate or low cost-effectiveness.The implementation of the 2014 hypertension guidelines for U.S. adults between the ages of 35 and 74 years could potentially prevent about 56,000 cardiovascular events and 13,000 deaths annually, while saving costs. Controlling hypertension in all patients with cardiovascular disease or stage 2 hypertension could be effective and cost-saving. (Funded by the National Heart, Lung, and Blood Institute and others.).

  View details for PubMedID 25629742

• Prognostic Implications of Microvascular and Macrovascular Abnormalities in Older Adults: Cardiovascular Health Study JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Kim, D., Grodstein, F., Newman, A. B., Chaves, P. M., Odden, M. C., Klein, R., Sarnak, M. J., Patel, K. V., Lipsitz, L. A. 2014; 69 (12): 1495–1502

  Abstract

  Microvascular and macrovascular abnormalities are frequently found on noninvasive tests performed in older adults. Their prognostic implications on disability and life expectancy have not been collectively assessed.This prospective study included 2,452 adults (mean age: 79.5 years) with available measures of microvascular (brain, retina, kidney) and macrovascular abnormalities (brain, carotid, coronary, peripheral artery) in the Cardiovascular Health Study. The burden of microvascular and macrovascular abnormalities was examined in relation to total, activity-of-daily-living disability-free, and severe disability-free life expectancies in the next 10 years (1999-2009).At 75 years, individuals with low burden of both abnormalities lived, on average, 8.71 years (95% confidence interval: 8.29, 9.12) of which 7.67 years (7.16, 8.17) were without disability. In comparison, individuals with high burden of both abnormalities had shortest total life expectancy (6.95 years [6.52, 7.37]; p < .001) and disability-free life expectancy (5.60 years [5.10, 6.11]; p < .001). Although total life expectancy was similarly reduced for those with high burden of either type of abnormalities (microvascular: 7.96 years [7.50, 8.42] vs macrovascular: 8.25 years [7.80, 8.70]; p = .10), microvascular abnormalities seemed to have larger impact than macrovascular abnormalities on disability-free life expectancy (6.45 years [5.90, 6.99] vs 6.96 years [6.43, 7.48]; p = .016). These results were consistent for severe disability-free life expectancy and in individuals without clinical cardiovascular disease.Considering both microvascular and macrovascular abnormalities from multiple noninvasive tests may provide additional prognostic information on how older adults spend their remaining life. Optimal clinical use of this information remains to be determined.

  View details for PubMedID 24864308

• Risk factors for cardiovascular disease across the spectrum of older age: The Cardiovascular Health Study ATHEROSCLEROSIS Odden, M. C., Shlipak, M. G., Whitson, H. E., Katz, R., Kearney, P. M., defilippi, C., Shastri, S., Sarnak, M. J., Siscovick, D. S., Cushman, M., Psaty, B. M., Newman, A. B. 2014; 237 (1): 336–42

  Abstract

  The associations of some risk factors with cardiovascular disease (CVD) are attenuated in older age; whereas others appear robust. The present study aimed to compare CVD risk factors across older age.Participants (n = 4883) in the Cardiovascular Health Study free of prevalent CVD, were stratified into three age groups: 65-74, 75-84, 85+ years. Traditional risk factors included systolic blood pressure (BP), LDL-cholesterol, HDL-cholesterol, obesity, and diabetes. Novel risk factors included kidney function, C-reactive protein (CRP), and N-terminal pro-B-type natriuretic peptide (NT pro-BNP).There were 1498 composite CVD events (stroke, myocardial infarction, and cardiovascular death) over 5 years. The associations of high systolic BP and diabetes appeared strongest, though both were attenuated with age (p-values for interaction = 0.01 and 0.002, respectively). The demographic-adjusted hazard ratios (HR) for elevated systolic BP were 1.79 (95% confidence interval: 1.49, 2.15), 1.59 (1.37, 1.85) and 1.10 (0.86, 1.41) in participants aged 65-74, 75-84, 85+, and for diabetes, 2.36 (1.89, 2.95), 1.55 (1.27, 1.89), 1.51 (1.10, 2.09). The novel risk factors had consistent associations with the outcome across the age spectrum; low kidney function: 1.69 (1.31, 2.19), 1.61 (1.36, 1.90), and 1.57 (1.16, 2.14) for 65-74, 75-84, and 85+ years, respectively; elevated CRP: 1.54 (1.28, 1.87), 1.33 (1.13, 1.55), and 1.51 (1.15, 1.97); elevated NT pro-BNP: 2.67 (1.96, 3.64), 2.71 (2.25, 3.27), and 2.18 (1.43, 3.45).The associations of most traditional risk factors with CVD were minimal in the oldest old, whereas diabetes, eGFR, CRP, and NT pro-BNP were associated with CVD across older age.

  View details for PubMedID 25303772

• Uric Acid Levels, Kidney Function, and Cardiovascular Mortality in US Adults: National Health and Nutrition Examination Survey (NHANES) 1988-1994 and 1999-2002 AMERICAN JOURNAL OF KIDNEY DISEASES Odden, M. C., Amadu, A., Smit, E., Lo, L., Peralta, C. A. 2014; 64 (4): 550–57

  Abstract

  Chronic kidney disease (CKD) and hyperuricemia often coexist, and both conditions are increasing in prevalence in the United States. However, their shared role in cardiovascular risk remains highly debated.Cross-sectional and longitudinal.Participants in the National Health and Nutrition Examination Survey (NHANES) from 1988 to 2002 (n = 10,956); data were linked to mortality data from the National Death Index through December 31, 2006.Serum uric acid concentration, categorized as the sex-specific lowest (< 25th), middle (25th- < 75th), and highest (≥ 75th) percentiles; and kidney function assessed by estimated glomerular filtration rate (eGFR) based on the CKD-EPI (CKD Epidemiology Collaboration) creatinine-cystatin C equation and urinary albumin-creatinine ratio (ACR).Cardiovascular death and all-cause mortality.Uric acid levels were correlated with eGFR(cr-cys) (r = -0.29; P < 0.001) and were correlated only slightly with ACR (r = 0.04; P < 0.001). There were 2,203 deaths up until December 31, 2006, of which 981 were due to cardiovascular causes. Overall, there was a U-shaped association between uric acid levels and cardiovascular mortality in both women and men, although the lowest risk of cardiovascular mortality occurred at a lower level of uric acid for women compared with men. There was an association between the highest quartile of uric acid level and cardiovascular mortality even after adjustment for potential confounders (HR, 1.48; 95% CI, 1.13-1.96), although this association was attenuated after adjustment for ACR and eGFR(cr-cys) (HR, 1.25; 95% CI, 0.89-1.75). The pattern of association between uric acid levels and all-cause mortality was similar.GFR not measured; mediating events were not observed.High uric acid level is associated with cardiovascular and all-cause mortality, although this relationship was no longer statistically significant after accounting for kidney function.

  View details for PubMedID 24906981

• Systolic and Diastolic Blood Pressure, Incident Cardiovascular Events, and Death in Elderly Persons The Role of Functional Limitation in the Cardiovascular Health Study HYPERTENSION Peralta, C. A., Katz, R., Newman, A. B., Psaty, B. M., Odden, M. C. 2014; 64 (3): 472–80

  Abstract

  Whether limitation in the ability to perform activities of daily living (ADL) or gait speed can identify elders in whom the association of systolic and diastolic blood pressure (DBP) with cardiovascular events (CVDs) and death differs is unclear. We evaluated whether limitation in ADL or gait speed modifies the association of systolic blood pressure or DBP with incident CVD (n=2358) and death (n=3547) in the Cardiovascular Health Study. Mean age was 78±5 and 21% reported limitation in ≥1 ADL. There were 778 CVD and 1289 deaths over 9 years. Among persons without and those with ADL limitation, systolic blood pressure was associated with incident CVD: hazard ratio [HR] (per 10-mm Hg increase) 1.08 (95% confidence interval, 1.03, 1.13) and 1.06 (0.97, 1.17), respectively. ADL modified the association of DBP with incident CVD. Among those without ADL limitation, DBP was weakly associated with incident CVD, HR 1.04 (0.79, 1.37) for DBP >80, compared with <65 mm Hg. Among those with ADL limitation, DBP was inversely associated with CVD: HR 0.65 (0.44, 0.96) for DBP 66 to 80 mm Hg and HR 0.49 (0.25, 0.94) for DBP >80, compared with DBP ≤65. Among people with ADL limitation, a DBP of 66 to 80 had the lowest risk of death, HR 0.72 (0.57, 0.91), compared with a DBP of ≤65. Associations did not vary by 15-feet walking speed. ADL can identify elders in whom diastolic hypotension is associated with higher cardiovascular risk and death. Functional status, rather than chronologic age alone, should inform design of hypertension trials in elders.

  View details for PubMedID 24935945

• Subclinical Vascular Disease Burden and Longer Survival JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Odden, M. C., Yee, L. M., Arnold, A. M., Sanders, J. L., Hirsch, C., deFilippi, C., Kizer, J. R., Inzitari, M., Newman, A. B. 2014; 62 (9): 1692–98

  Abstract

  To determine the contribution of gradations of subclinical vascular disease (SVD) to the likelihood of longer survival and to determine what allows some individuals with SVD to live longer.Cohort study.Cardiovascular Health Study.Individuals born between June 30, 1918, and June 30, 1921 (N = 2,082; aged 70-75 at baseline (1992-93)).A SVD index was scored as 0 for no abnormalities, 1 for mild abnormalities, and 2 for severe abnormalities on ankle-arm index, electrocardiogram, and common carotid intima-media thickness measured at baseline. Survival groups were categorized as 80 and younger, 81 to 84, 85 to 89, and 90 and older.A 1-point lower SVD score was associated with 1.22 greater odds (95% confidence interval = 1.14-1.31) of longer survival, independent of potential confounders. This association was unchanged after adjustment for intermediate incident cardiovascular events. There was suggestion of an interaction between kidney function, smoking, and C-reactive protein and SVD; the association between SVD and longer survival appeared to be modestly greater in persons with poor kidney function, inflammation, or a history of smoking.A lower burden of SVD is associated with longer survival, independent of intermediate cardiovascular events. Abstinence from smoking, better kidney function, and lower inflammation may attenuate the effects of higher SVD and promote longer survival.

  View details for PubMedID 25243681

• Kidney Function and Cognitive Health in Older Adults: The Cardiovascular Health Study AMERICAN JOURNAL OF EPIDEMIOLOGY Darsie, B., Shlipak, M. G., Sarnak, M. J., Katz, R., Fitzpatrick, A. L., Odden, M. C. 2014; 180 (1): 68–75

  Abstract

  Recent evidence has demonstrated the importance of kidney function in healthy aging. We examined the association between kidney function and change in cognitive function in 3,907 participants in the Cardiovascular Health Study who were recruited from 4 US communities and studied from 1992 to 1999. Kidney function was measured by cystatin C-based estimated glomerular filtration rate (eGFRcys). Cognitive function was assessed using the Modified Mini-Mental State Examination and the Digit Symbol Substitution Test, which were administered up to 7 times during annual visits. There was an association between eGFRcys and change in cognitive function after adjustment for confounders; persons with an eGFRcys of less than 60 mL/minute/1.73 m(2) had a 0.64 (95% confidence interval: 0.51, 0.77) points/year faster decline in Modified Mini-Mental State Examination score and a 0.42 (95% confidence interval: 0.28, 0.56) points/year faster decline in Digit Symbol Substitution Test score compared with persons with an eGFRcys of 90 or more mL/minute/1.73 m(2). Additional adjustment for intermediate cardiovascular events modestly affected these associations. Participants with an eGFRcys of less than 60 mL/minute/1.73 m(2) had fewer cognitive impairment-free life-years on average compared with those with eGFRcys of 90 or more mL/minute/1.73 m(2), independent of confounders and mediating cardiovascular events (mean difference = -0.44, 95% confidence interval: -0.62, -0.26). Older adults with lower kidney function are at higher risk of worsening cognitive function.

  View details for DOI 10.1093/aje/kwu102

  View details for Web of Science ID 000339808200010

  View details for PubMedID 24844846

  View details for PubMedCentralID PMC4070934

• Trends in Hypertension Prevalence, Awareness, Treatment, and Control Among US Adults 80 Years and Older, 1988-2010 JOURNAL OF CLINICAL HYPERTENSION Bromfield, S. G., Bowling, C., Tanner, R. M., Peralta, C. A., Odden, M. C., Oparil, S., Muntner, P. 2014; 16 (4): 270–76

  Abstract

  The authors examined trends in systolic blood pressure (SBP) and diastolic blood pressure (DBP) and the prevalence, awareness, treatment, and control of hypertension in 1988-1994 (n=1164), 1999-2004 (n=1,026), and 2005-2010 (n=1048) among US adults 80 years and older in serial National Health and Nutrition Examination Surveys. Hypertension was defined as SBP ≥140 mm Hg, DBP ≥90 mm Hg, or use of antihypertensive medication. Awareness and treatment were defined by self-report and control as SBP/DBP<140/90 mm Hg. Mean SBP decreased from 147.3 mm Hg to 140.1 mm Hg and mean DBP from 70.2 mm Hg to 59.4 mm Hg between 1988-1994 and 2005-2010. The prevalence, awareness, and treatment of hypertension each increased over time. Controlled hypertension increased from 30.4% in 1988-1994 to 53.1% in 2005-2010. The proportion of patients taking 3 classes of antihypertensive medication increased from 7.0% to 30.9% between 1988-1994 and 2005-2010. Increases in awareness, treatment, and control of hypertension and antihypertensive polypharmacy have been observed among very old US adults.

  View details for DOI 10.1111/jch.12281

  View details for Web of Science ID 000334290700012

  View details for PubMedID 24621268

• Health Benefits of Reducing Sugar-Sweetened Beverage Intake in High Risk Populations of California: Results from the Cardiovascular Disease (CVD) Policy Model PLOS ONE Mekonnen, T. A., Odden, M. C., Coxson, P. G., Guzman, D., Lightwood, J., Wang, Y., Bibbins-Domingo, K. 2013; 8 (12): e81723

  Abstract

  Consumption of sugar-sweetened beverage (SSB) has risen over the past two decades, with over 10 million Californians drinking one or more SSB per day. High SSB intake is associated with risk of type 2 diabetes, obesity, hypertension, and coronary heart disease (CHD). Reduction of SSB intake and the potential impact on health outcomes in California and among racial, ethnic, and low-income sub-groups has not been quantified.We projected the impact of reduced SSB consumption on health outcomes among all Californians and California subpopulations from 2013 to 2022. We used the CVD Policy Model - CA, an established computer simulation of diabetes and heart disease adapted to California. We modeled a reduction in SSB intake by 10-20% as has been projected to result from proposed penny-per-ounce excise tax on SSB and modeled varying effects of this reduction on health parameters including body mass index, blood pressure, and diabetes risk. We projected avoided cases of diabetes and CHD, and associated health care cost savings in 2012 US dollars.Over the next decade, a 10-20% SSB consumption reduction is projected to result in a 1.8-3.4% decline in the new cases of diabetes and an additional drop of 0.5-1% in incident CHD cases and 0.5-0.9% in total myocardial infarctions. The greatest reductions are expected in African Americans, Mexican Americans, and those with limited income regardless of race and ethnicity. This reduction in SSB consumption is projected to yield $320-620 million in medical cost savings associated with diabetes cases averted and an additional savings of $14-27 million in diabetes-related CHD costs avoided.A reduction of SSB consumption could yield substantial population health benefits and cost savings for California. In particular, racial, ethnic, and low-income subgroups of California could reap the greatest health benefits.

  View details for PubMedID 24349119

• Kidney Function and Prevalent and Incident Frailty CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Dalrymple, L. S., Katz, R., Rifkin, D. E., Siscovick, D., Newman, A. B., Fried, L. F., Sarnak, M. J., Odden, M. C., Shlipak, M. G. 2013; 8 (12): 2091–99

  Abstract

  Kidney disease is associated with physiologic changes that may predispose to frailty. This study sought to investigate whether lower levels of kidney function were associated with prevalent or incident frailty in Cardiovascular Health Study (CHS) participants.CHS enrolled community-dwelling adults age ≥65 years between 1989-1990 and 1992-1993. To examine prevalent frailty, included were 4150 participants without stroke, Parkinson disease, prescribed medications for Alzheimer disease or depression, or severely impaired cognition. To examine incident frailty, included were a subset of 3459 participants without baseline frailty or development of exclusion criteria during follow-up. The primary predictor was estimated GFR (eGFR) calculated using serum cystatin C (eGFR(cys)). Secondary analyses examined eGFR using serum creatinine (eGFR(SCr)). Outcomes were prevalent frailty and incident frailty at 4 years of follow-up. Frailty was ascertained on the basis of weight loss, exhaustion, weakness, slowness, and low physical activity.The mean age was 75 years and the median eGFR(cys) was 73 ml/min per 1.73 m(2). Among participants with an eGFR(cys) <45 ml/min per 1.73 m(2), 24% had prevalent frailty. In multivariable analysis and compared with eGFR(cys) ≥90 ml/min per 1.73 m(2), eGFR(cys) categories of 45-59 (odds ratio [OR], 1.80; 95% confidence interval [CI], 1.17 to 2.75) and 15-44 (OR, 2.87; 95% CI, 1.72 to 4.77) were associated with higher odds of frailty, whereas 60-75 (OR, 1.14; 95% CI, 0.76 to 1.70) was not. In multivariable analysis, eGFR(cys) categories of 60-75 (incidence rate ratio [IRR], 1.72; 95% CI, 1.07 to 2.75) and 15-44 (IRR, 2.28; 95% CI, 1.23 to 4.22) were associated with higher incidence of frailty whereas 45-59 (IRR, 1.53; 95% CI, 0.90 to 2.60) was not. Lower levels of eGFR(SCr) were not associated with higher risk of prevalent or incident frailty.In community-dwelling elders, lower eGFR(cys) was associated with a higher risk of prevalent and incident frailty whereas lower eGFR(SCr) was not. These findings highlight the importance of considering non-GFR determinants of kidney function.

  View details for DOI 10.2215/CJN.02870313

  View details for Web of Science ID 000327951100010

  View details for PubMedID 24178972

  View details for PubMedCentralID PMC3848393

• Hypertension and low HDL cholesterol were associated with reduced kidney function across the age spectrum: a collaborative study ANNALS OF EPIDEMIOLOGY Odden, M. C., Tager, I. B., Gansevoort, R. T., Bakker, S. L., Fried, L. F., Newman, A. B., Katz, R., Satterfield, S., Harris, T. B., Sarnak, M. J., Siscovick, D., Shlipak, M. G. 2013; 23 (3): 106–11

  Abstract

  To determine if the associations among established risk factors and reduced kidney function vary by age.We pooled cross-sectional data from 14,788 nondiabetics aged 40 to 100 years in 4 studies: Cardiovascular Health Study, Health, Aging, and Body Composition Study, Multi-Ethnic Study of Atherosclerosis, and Prevention of Renal and Vascular End-Stage Disease cohort.Hypertension and low high-density lipoprotein (HDL) cholesterol were associated with reduced cystatin C-based estimated glomerular filtration rate (eGFR) across the age spectrum. In adjusted analyses, hypertension was associated with a 2.3 (95% confidence interval [CI], 0.1, 4.4), 5.1 (95% CI, 4.1, 6.1), and 6.9 (95% CI, 3.0, 10.4) mL/min/1.73 m(2) lower eGFR in participants 40 to 59, 60 to 79, and at least 80 years, respectively (P for interaction < .001). The association of low HDL cholesterol with reduced kidney function was also greater in the older age groups: 4.9 (95% CI, 3.5, 6.3), 7.1 (95% CI, 6.0, 8.3), 8.9 (95% CI, 5.4, 11.9) mL/min/1.73 m(2) (P for interaction < .001). Smoking and obesity were associated with reduced kidney function in participants under 80 years. All estimates of the potential population impact of the risk factors were modest.Hypertension, obesity, smoking, and low HDL cholesterol are modestly associated with reduced kidney function in nondiabetics. The associations of hypertension and HDL cholesterol with reduced kidney function seem to be stronger in older adults.

  View details for PubMedID 23313266

• THE ASSOCIATION OF RESILIENCE WITH MENTAL AND PHYSICAL HEALTH AMONG OLDER AMERICAN INDIANS: THE NATIVE ELDER CARE STUDY AMERICAN INDIAN AND ALASKA NATIVE MENTAL HEALTH RESEARCH Schure, M. B., Odden, M., Goins, R. 2013; 20 (2): 27–41

  Abstract

  We examined the association of resilience with measures of mental and physical health in a sample of older American Indians (AIs). A validated scale measuring resilience was administered to 185 noninstitutionalized AIs aged>=55 years. Unadjusted analyses revealed that higher levels of resilience were associated with lower levels of depressive symptomatology and chronic pain, and with higher levels of mental and physical health. Resilience remained significantly associated with depressive symptomatology after controlling for demographic and other health measures. Our findings suggest that resilience among older AIs has important implications for some aspects of mental and physical health.

  View details for Web of Science ID 000322082700002

  View details for PubMedID 23824641

  View details for PubMedCentralID PMC3805026

• Association Between Chronic Kidney Disease Detected Using Creatinine and Cystatin C and Death and Cardiovascular Events in Elderly Mexican Americans: The Sacramento Area Latino Study on Aging JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Peralta, C. A., Lee, A., Odden, M. C., Lopez, L., Al Hazzouri, A., Neuhaus, J., Haan, M. N. 2013; 61 (1): 90–95

  Abstract

  Creatinine, the current clinical standard to detect chronic kidney disease (CKD), is biased by muscle mass, age and race. The authors sought to determine whether cystatin C, an alternative marker of kidney function less biased by these factors, can identify elderly Mexican Americans with CKD who are at high risk for death and cardiovascular disease.Longitudinal, with mean follow-up of 6.8 years.Sacramento Area Latino Study of Aging (SALSA).One thousand four hundred and thirty five Mexican Americans aged 60 to 101.Estimated glomerular filtration rate (eGFR, mL/min per 1.73 m(2)) was determined according to creatinine (eGFRcreat) and cystatin C (eGFRcys), and participants were classified into four mutually exclusive categories: CKD neither (eGFRcreat ≥60 mL/min per 1.73 m(2); eGFRcys ≥60 mL/min per 1.73 m(2)), CKD creatinine only (eGFRcreat <60 mL/min per 1.73 m(2); eGFRcys ≥60 mL/min per 1.73 m(2)), CKD cystatin only (eGFRcreat ≥60 mL/min per 1.73 m(2); eGFRcys <60), and CKD both (eGFRcreat <60 mL/min per 1.73 m(2); GFRcys <60 mL/min per 1.73 m(2)). The associations between each CKD classification and all-cause death and cardiovascular (CV) death were studied using Cox regression.At baseline, mean age was 71 ± 7; 481 (34%) had diabetes mellitus, and 980 (68%) had hypertension. Persons with CKD both had higher risk for all-cause (HR = 2.30, 95% confidence interval (CI) = 1.78-2.98) and CV disease (CVD) (HR = 2.75, 95% CI = 1.96-3.86) death than CKD neither after full adjustment. Persons with CKD cystatin C only were also at greater risk of all-cause (HR = 1.91, 95% CI = 1.37-2.67) and CV (HR = 2.56, 95% CI = 1.64-3.99) death than CKD neither. In contrast, persons with CKD creatinine only were not at greater risk for CV death (HR = 1.39, 95% CI = 0.71-2.72) but were at higher risk for all-cause death (HR = 1.95, 95% CI = 1.27-2.98).Cystatin C may be a useful alternative to creatinine for detecting high risk of death and CVD in elderly Mexican Americans with CKD.

  View details for DOI 10.1111/jgs.12040

  View details for Web of Science ID 000313715600016

  View details for PubMedID 23252993

  View details for PubMedCentralID PMC3545054

• The Association of Blood Pressure and Mortality Differs by Self-reported Walking Speed in Older Latinos JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Odden, M. C., Covinsky, K. E., Neuhaus, J. M., Mayeda, E. R., Peralta, C. A., Haan, M. N. 2012; 67 (9): 977–83

  Abstract

  In some older adults, higher blood pressure (BP) is associated with a lower risk of mortality. We hypothesized that higher BP would be associated with greater mortality in high-functioning elders and lower mortality in elders with lower functional status.Participants were 1,562 Latino adults aged 60-101 years in the Sacramento Area Latino Study on Aging. Functional status was measured by self-reported walking speed, and BP was measured by automatic sphygmomanometer. Death information was determined from vital statistics records.There were 442 deaths from 1998 to 2010; 53% were cardiovascular. Mean BP levels (mmHg) varied across fast, medium, and slow walkers: 136, 139, and 140 mmHg (systolic), p = .02 and 75, 76, and 77 mmHg (diastolic), p = .08, respectively. The relationship between systolic BP and mortality varied by self-reported walking speed: The adjusted hazard ratio for mortality in slow walkers was 0.96 per 10 mmHg higher systolic BP (95% confidence interval: 0.89, 1.02) and 1.29 (95% confidence interval: 1.08, 1.55) in fast walkers (p value for interaction <.001). We found a similar pattern for diastolic BP, although the interaction did not reach statistical significance; the adjusted hazard ratio per 10 mmHg higher diastolic BP was 0.89 (95% confidence interval: 0.78, 1.02) in slow walkers and 1.20 (95% confidence interval: 0.82, 1.76) in fast walkers (p value for interaction = .06).In high-functioning older adults, elevated systolic BP is a risk factor for all-cause mortality. If confirmed in other studies, the assessment of functional status may help to identify persons who are most at-risk for adverse outcomes related to high BP.

  View details for PubMedID 22389463

• Rethinking the Association of High Blood Pressure With Mortality in Elderly Adults The Impact of Frailty ARCHIVES OF INTERNAL MEDICINE Odden, M. C., Peralta, C. A., Haan, M. N., Covinsky, K. E. 2012; 172 (15): 1162–68

  Abstract

  The association of hypertension and mortality is attenuated in elderly adults. Walking speed, as a measure of frailty, may identify which elderly adults are most at risk for the adverse effects of hypertension. We hypothesized that elevated blood pressure (BP) would be associated with a greater risk of mortality in faster-, but not slower-, walking older adults.Participants included 2340 persons 65 years and older in the National Health and Nutrition Examination Survey, 1999-2000 and 2001-2002. Mortality data were linked to death certificates in the National Death Index. Walking speed was measured over a 20-ft (6 m) walk and classified as faster (≥ 0.8 m/s [n = 1307]), slower (n = 790), or incomplete (n = 243). Potential confounders included age, sex, race, survey year, lifestyle and physiologic variables, health conditions, and antihypertensive medication use.Among the participants, there were 589 deaths through December 31, 2006. The association between BP and mortality varied by walking speed. Among faster walkers, those with elevated systolic BP (≥ 140 mm Hg) had a greater adjusted risk of mortality compared with those without (hazard ratio [HR], 1.35; 95% CI, 1.03-1.77). Among slower walkers, neither elevated systolic nor diastolic BP (≥ 90 mm Hg) was associated with mortality. In participants who did not complete the walk test, elevated BP was strongly and independently associated with a lower risk of death: HR, 0.38; 95% CI, 0.23-0.62 (systolic); and HR, 0.10; 95% CI, 0.01-0.81 (diastolic).Walking speed could be a simple measure to identify elderly adults who are most at risk for adverse outcomes related to high BP.

  View details for PubMedID 22801930

• Kidney Function and Mortality in Octogenarians: Cardiovascular Health Study All Stars JOURNAL OF THE AMERICAN GERIATRICS SOCIETY Shastri, S., Katz, R., Rifkin, D. E., Fried, L. F., Odden, M. C., Peralta, C. A., Chonchol, M., Siscovick, D., Shlipak, M. G., Newman, A. B., Sarnak, M. J. 2012; 60 (7): 1201–7

  Abstract

  To examine the association between kidney function and all-cause mortality in octogenarians.Retrospective analysis of prospectively collected data.Community.Serum creatinine and cystatin C were measured in 1,053 Cardiovascular Health Study (CHS) All Stars participants.Estimated glomerular filtration rate (eGFR) was determined using the Chronic Kidney Disease Epidemiology Collaboration creatinine (eGFR(CR) ) and cystatin C one-variable (eGFR(CYS) ) equations. The association between quintiles of kidney function and all-cause mortality was analyzed using unadjusted and adjusted Cox proportional hazards models.Mean age of the participants was 85, 64% were female, 66% had hypertension, 14% had diabetes mellitus, and 39% had prevalent cardiovascular disease. There were 154 deaths over a median follow-up of 2.6 years. The association between eGFR(CR) and all-cause mortality was U-shaped. In comparison with the reference quintile (64-75 mL/min per 1.73 m(2) ), the highest (≥ 75 mL/min per 1.73 m(2) ) and lowest (≤ 43 mL/min per 1.73 m(2) ) quintiles of eGFR(CR) were independently associated with mortality (hazard ratio (HR) = 2.49, 95% confidence interval (CI) = 1.36-4.55; HR = 2.28, 95% CI = 1.26-4.10, respectively). The association between eGFR(CYS) and all-cause mortality was linear in those with eGFR(CYS) of less than 60 mL/min per 1.73 m(2) , and in the multivariate analyses, the lowest quintile of eGFR(CYS) (<52 mL/min per 1.73 m(2) ) was significantly associated with mortality (HR = 2.04, 95% CI = 1.12-3.71) compared with the highest quintile (>0.88 mL/min per 1.73 m(2) ).Moderate reduction in kidney function is a risk factor for all-cause mortality in octogenarians. The association between eGFR(CR) and all-cause mortality differed from that observed with eGFR(CYS) ; the relationship was U-shaped for eGFR(CR) , whereas the risk was primarily present in the lowest quintile for eGFR(CYS) .

  View details for DOI 10.1111/j.1532-5415.2012.04046.x

  View details for Web of Science ID 000306311600001

  View details for PubMedID 22724391

  View details for PubMedCentralID PMC3902776

• The Impact of the Aging Population on Coronary Heart Disease in the United States AMERICAN JOURNAL OF MEDICINE Odden, M. C., Coxson, P. G., Moran, A., Lightwood, J. M., Goldman, L., Bibbins-Domingo, K. 2011; 124 (9): 827-U1506

  Abstract

  The demographic shift toward an older population in the United States will result in a higher burden of coronary heart disease, but the increase has not been quantified in detail. We sought to estimate the impact of the aging US population on coronary heart disease.We used the Coronary Heart Disease Policy Model, a Markov model of the US population between 35 and 84 years of age, and US Census projections to model the age structure of the population between 2010 and 2040.Assuming no substantive changes in risks factors or treatments, incident coronary heart disease is projected to increase by approximately 26%, from 981,000 in 2010 to 1,234,000 in 2040, and prevalent coronary heart disease by 47%, from 11.7 million to 17.3 million. Mortality will be affected strongly by the aging population; annual coronary heart disease deaths are projected to increase by 56% over the next 30 years, from 392,000 to 610,000. Coronary heart disease-related health care costs are projected to rise by 41% from $126.2 billion in 2010 to $177.5 billion in 2040 in the United States. It may be possible to offset the increase in disease burden through achievement of Healthy People 2010/2020 objectives or interventions that substantially reduce obesity, blood pressure, or cholesterol levels in the population.Without considerable changes in risk factors or treatments, the aging of the US population will result in a sizeable increase in coronary heart disease incidence, prevalence, mortality, and costs. Health care stakeholders need to plan for the future age-related health care demands of coronary heart disease.

  View details for DOI 10.1016/j.amjmed.2011.04.010

  View details for Web of Science ID 000294043100025

  View details for PubMedID 21722862

  View details for PubMedCentralID PMC3159777

• Longitudinal Association of Depressive Symptoms with Rapid Kidney Function Decline and Adverse Clinical Renal Disease Outcomes CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Kop, W. J., Seliger, S. L., Fink, J. C., Katz, R., Odden, M. C., Fried, L. F., Rifkin, D. E., Sarnak, M. J., Gottdiener, J. S. 2011; 6 (4): 834–44

  Abstract

  Depression is a risk indicator for adverse outcomes in dialysis patients, but its prognostic impact in individuals who are not yet on dialysis is unknown. This study examines whether depressive symptoms are longitudinally associated with renal function decline, new-onset chronic kidney disease (CKD), ESRD, or hospitalization with acute kidney injury (AKI).Depressive symptoms were measured in a longitudinal cohort study with the 10-item Centers for Epidemiologic Studies Depression scale using a previously validated cut-off value (≥8). CKD at study entry and during follow-up was defined as an estimated GFR (eGFR) < 60 ml/min per m(2). Outcomes were rapid decline in eGFR (>3 ml/min per m(2) per year), new-onset CKD, ESRD (U.S. Renal Data System-based), and AKI (based on adjudicated medical record review). The median follow-up duration was 10.5 years.Depressed participants (21.2%) showed a higher prevalence of CKD at baseline compared with nondepressed participants in multivariable analysis. Depression was associated with a subsequent risk of rapid decline in eGFR, incident ESRD, and AKI, but not incident CKD in unadjusted models. In multivariable analyses, only associations of depressive symptoms with AKI remained significant.Elevated depressive symptoms are associated with subsequent adverse renal disease outcomes. The depression-related elevated risk of AKI was independent of traditional renal disease risk factors and may in part be explained by the predictive value of depression for acute coronary syndromes and heart failure hospitalizations that can be complicated by AKI.

  View details for DOI 10.2215/CJN.03840510

  View details for Web of Science ID 000289223600022

  View details for PubMedID 21393483

  View details for PubMedCentralID PMC3069377

• Antihypertensive Medication Use and Change in Kidney Function in Elderly Adults: A Marginal Structural Model Analysis INTERNATIONAL JOURNAL OF BIOSTATISTICS Odden, M. C., Tager, I. B., van der Laan, M. J., Delaney, J. C., Peralta, C. A., Katz, R., Sarnak, M. J., Psaty, B. M., Shlipak, M. G. 2011; 7 (1): Article 34

  Abstract

  The evidence for the effectiveness of antihypertensive medication use for slowing decline in kidney function in older persons is sparse. We addressed this research question by the application of novel methods in a marginal structural model.Change in kidney function was measured by two or more measures of cystatin C in 1,576 hypertensive participants in the Cardiovascular Health Study over 7 years of follow-up (1989-1997 in four U.S. communities). The exposure of interest was antihypertensive medication use. We used a novel estimator in a marginal structural model to account for bias due to confounding and informative censoring.The mean annual decline in eGFR was 2.41 ± 4.91 mL/min/1.73 m(2). In unadjusted analysis, antihypertensive medication use was not associated with annual change in kidney function. Traditional multivariable regression did not substantially change these estimates. Based on a marginal structural analysis, persons on antihypertensives had slower declines in kidney function; participants had an estimated 0.88 (0.13, 1.63) ml/min/1.73 m(2) per year slower decline in eGFR compared with persons on no treatment. In a model that also accounted for bias due to informative censoring, the estimate for the treatment effect was 2.23 (-0.13, 4.59) ml/min/1.73 m(2) per year slower decline in eGFR.In summary, estimates from a marginal structural model suggested that antihypertensive therapy was associated with preserved kidney function in hypertensive elderly adults. Confirmatory studies may provide power to determine the strength and validity of the findings.

  View details for PubMedID 22049266

• Physical Functioning in Elderly Persons With Kidney Disease ADVANCES IN CHRONIC KIDNEY DISEASE Odden, M. C. 2010; 17 (4): 348–57

  Abstract

  Poor physical functioning in dialysis patients has been well documented. Several studies have reported an association of poor kidney function with adverse physical functioning outcomes, even in elderly persons with mild decrements in kidney function. These associations have been observed across multiple domains of physical function. This review summarizes the current research on physical functioning in kidney disease, with a special focus on elderly populations. Elderly persons with kidney disease may especially be at a high risk for disability and other adverse outcomes because of the dual effects of aging and kidney dysfunction on physical functioning. Both the correction of anemia and physical activity are effective for at least moderate improvements in physical function although these studies have been conducted primarily in younger persons with less comorbidity. The evidence that exists on exercise interventions in older adults with kidney disease is promising, although this population has been underrepresented in trials to date. More research on potential interventions to prevent or reduce poor physical functioning is needed in elderly persons with kidney disease.

  View details for DOI 10.1053/j.ackd.2010.02.002

  View details for Web of Science ID 000279804000009

  View details for PubMedID 20610362

• Age and cystatin C in healthy adults: a collaborative study NEPHROLOGY DIALYSIS TRANSPLANTATION Odden, M. C., Tager, I. B., Gansevoort, R. T., Bakker, S. L., Katz, R., Fried, L. F., Newman, A. B., Canada, R. B., Harris, T., Sarnak, M. J., Siscovick, D., Shlipak, M. G. 2010; 25 (2): 463–69

  Abstract

  Kidney function declines with age, but a substantial portion of this decline has been attributed to the higher prevalence of risk factors for kidney disease at older ages. The effect of age on kidney function has not been well described in a healthy population across a wide age spectrum.The authors pooled individual-level cross-sectional data from 18 253 persons aged 28-100 years in four studies: the Cardiovascular Health Study; the Health, Aging and Body Composition Study; the Multi-Ethnic Study of Atherosclerosis and the Prevention of Renal and Vascular End-Stage Disease cohort. Kidney function was measured by cystatin C. Clinical risk factors for kidney disease included diabetes, hypertension, obesity, smoking, coronary heart disease, cerebrovascular disease, peripheral arterial disease and heart failure.Across the age range, there was a strong, non-linear association of age with cystatin C concentration. This association was substantial, even among participants free of clinical risk factors for kidney disease; mean cystatin C levels were 46% higher in participants 80 and older compared with those <40 years (1.06 versus 0.72 mg/L, P < 0.001). Participants with one or more risk factors had higher cystatin C concentrations for a given age, and the age association was slightly stronger (P < 0.001 for age and risk factor interaction).There is a strong, non-linear association of age with kidney function, even in healthy individuals. An important area for research will be to investigate the mechanisms that lead to deterioration of kidney function in apparently healthy persons.

  View details for DOI 10.1093/ndt/gfp474

  View details for Web of Science ID 000273891600024

  View details for PubMedID 19749145

  View details for PubMedCentralID PMC2904248

• Serum Creatinine and Functional Limitation in Elderly Persons JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES Odden, M. C., Shlipak, M. G., Tager, I. B. 2009; 64 (3): 370–76

  Abstract

  Creatinine is a commonly used measure of kidney function, but serum levels are also influenced by muscle mass. We hypothesized that higher serum creatinine would be associated with self-reported functional limitation in community-dwelling elderly.Subjects (n = 1,553) were participants in the Study of Physical Performance and Age-Related Changes in Sonomans, a cohort to study aging and physical function. We explored three strategies to account for the effects of muscle mass on serum creatinine.We observed a J-shaped association of creatinine with functional limitation. Above the study-specific mean creatinine (0.97 mg/dL in women and 1.15 mg/dL in men), the unadjusted odds ratio of functional limitation per standard deviation (0.20 mg/dL in women and 0.23 mg/dL in men) higher creatinine was 2.27 (95% confidence interval [CI] 1.75-2.94, p < .001) in women and 1.42 (95% CI 1.12-1.80, p = .003) in men. This association was inverted in persons with creatinine levels below the mean. Adjustment for muscle mass did not have an important effect on the association between creatinine and functional limitation. These associations remained after multivariable adjustment for demographics and health conditions but were statistically significant only in women.In elderly adults, higher creatinine levels are associated with functional limitation, consistent with prior literature that has demonstrated reduced physical performance in persons with kidney disease. However, the association of low creatinine levels with functional limitation suggests that creatinine levels are influenced by factors other than kidney function and muscle mass in the elderly.

  View details for DOI 10.1093/gerona/gln037

  View details for Web of Science ID 000264190500006

  View details for PubMedID 19181716

  View details for PubMedCentralID PMC2655007

• Health, aging, and body composition study: Diabetes-related complications, glycemic control, and falls in older adults (vol 31, pg 391, 2008) DIABETES CARE Schwartz, A., Vittinghoff, E., Sellmeyer, D. E., Feingold, K. R., de Rekeneire, N., Strotmeyer, E. S., Shorr, R., Vinik, A., Odden, M. C., Park, S. W., Faulkner, K. A., Harris, T. B., Health Aging Body Composition 2008; 31 (5): 1089

  View details for Web of Science ID 000256016300048

• Diabetes-related complications, glycemic control, and falls in older adults Schwartz, A. V., Vittinghoff, E., Sellmeyer, D. E., Feingold, K. R., de Rekeneire, N., Strotmeyer, E. S., Shorr, R. I., Vinik, A. I., Odden, M. C., Park, S., Faulkner, K. A., Harris, T. B., Hlth Aging Body Composition Study AMER DIABETES ASSOC. 2008: 391–96

  Abstract

  Older adults with type 2 diabetes are more likely to fall, but little is known about risk factors for falls in this population. We determined whether diabetes-related complications or treatments are associated with risk of falls in older diabetic adults.In the Health, Aging, and Body Composition cohort of well-functioning older adults, participants reported falls in the previous year at annual visits. Odds ratios (ORs) for more frequent falls among 446 diabetic participants whose mean age was 73.6 years, with an average follow-up of 4.9 years, were estimated with continuation ratio models.In the first year, 23[corrected]% reported falling; 22, 26, 30[corrected], and 31[corrected]% fell in subsequent years. In adjusted models, reduced peroneal nerve response amplitude (OR 1.50 -95% CI 1.07-2.12], worst quartile versus others); higher cystatin-C, a marker of reduced renal function (1.38 [1.11-1.71], for 1 SD increase); poorer contrast sensitivity (1.41 [0.97-2.04], worst quartile versus others); and low A1C in insulin users (4.36 [1.32-14.46], A1C 8%) were associated with risk of falls. In those using oral hypoglycemic medications but not insulin, low A1C was not associated with risk of falls (1.29 [0.65-2.54], A1C 8%). Adjustment for physical performance explained some, but not all, of these associations.In older diabetic adults, reducing diabetes-related complications may prevent falls. Achieving lower A1C levels with oral hypoglycemic medications was not associated with more frequent falls, but, among those using insulin, A1C

  View details for DOI 10.2337/dc07-1152

  View details for Web of Science ID 000253801100003

  View details for PubMedID 18056893

  View details for PubMedCentralID PMC2288549

• Cystatin C level as a marker of kidney function in human immunodeficiency virus infection - The FRAM study ARCHIVES OF INTERNAL MEDICINE Odden, M. C., Scherzer, R., Bacchetti, P., Szczech, L., Sidney, S., Grunfeld, C., Shlipak, M. G. 2007; 167 (20): 2213–19

  Abstract

  Although studies have reported a high prevalence of end-stage renal disease in human immunodeficiency virus (HIV)-infected individuals, little is known about moderate impairments in kidney function. Cystatin C measurement may be more sensitive than creatinine for detecting impaired kidney function in persons with HIV.We evaluated kidney function in the Fat Redistribution and Metabolic Change in HIV Infection (FRAM) cohort, a representative sample of 1008 HIV-infected persons and 290 controls from the Coronary Artery Risk Development in Young Adults (CARDIA) study in the United States.Cystatin C level was elevated in HIV-infected individuals; the mean +/- SD cystatin C level was 0.92 +/- 0.22 mg/L in those infected with HIV and 0.76 +/- 0.15 mg/L in controls (P < .001). In contrast, both mean creatinine levels and estimated glomerular filtration rates appeared similar in HIV-infected individuals and controls (0.87 +/- 0.21 vs 0.85 +/- 0.19 mg/dL [to convert to micromoles per liter, multiply by 88.4] [P = .35] and 110 +/- 26 vs 106 +/- 23 mL/min/1.73 m(2) [P = .06], respectively). Persons with HIV infection were more likely to have a cystatin C level greater than 1.0 mg/L (OR, 9.8; 95% confidence interval, 4.4-22.0 [P <.001]), a threshold demonstrated to be associated with increased risk for death and cardiovascular and kidney disease. Among participants with HIV, potentially modifiable risk factors for kidney disease, hypertension, and low high-density lipoprotein concentration were associated with a higher cystatin C level, as were lower CD4 lymphocyte count and coinfection with hepatitis C virus (all P < .001).Individuals infected with HIV had substantially worse kidney function when measured by cystatin C level compared with HIV-negative controls, whereas mean creatinine levels and estimated glomerular filtration rates were similar. Cystatin C measurement could be a useful clinical tool to identify HIV-infected persons at increased risk for kidney and cardiovascular disease.

  View details for DOI 10.1001/archinte.167.20.2213

  View details for Web of Science ID 000250806200008

  View details for PubMedID 17998494

  View details for PubMedCentralID PMC3189482

• Kidney function and markers of inflammation in elderly persons without chronic kidney disease: The health, aging, and body composition study KIDNEY INTERNATIONAL Keller, C. R., Odden, M. C., Fried, L. F., Newman, A. B., Angleman, S., Green, C. A., Cummings, S. R., Harris, T. B., Shlipak, M. G. 2007; 71 (3): 239–44

  Abstract

  Inflammatory markers are elevated in persons with estimated glomerular filtration rates less than 60 ml/min/1.73 m2. As cystatin C may detect small changes in kidney function not detected by estimated glomerular filtration rate, we evaluated the association between cystatin C and serum markers of inflammation in older adults with estimated glomerular filtration rate >or=60. This is an analysis using measures from the Health, Aging, and Body Composition Study, a cohort of well-functioning adults aged 70-79 years. Cystatin C correlated with all five inflammatory biomarkers: C-reactive protein (r=0.08), interleukin-6 (r=0.19), tumor necrosis factor alpha (TNF-alpha) (r=0.41), soluble TNF receptor 1 (STNF-R1) (r=0.61), and soluble TNF receptor 2 (STNF-R2) (r=0.54); P<0.0005 for all. In adjusted analyses, cystatin C concentrations appeared to have stronger associations with each biomarker compared with estimated glomerular filtration rate or serum creatinine. Participants with a cystatin C>or=1.0 mg/l had significantly higher levels of all five biomarkers compared to those with a cystatin C<1.0 (mean differences ranging 16-29%, all P<0.05). Cystatin C has a linear association with inflammatory biomarkers in an ambulatory elderly cohort with estimated glomerular filtration rates >or=60; associations are particularly strong with TNF-alpha and the STNF-R.

  View details for DOI 10.1038/sj.ki.5002042

  View details for Web of Science ID 000243730800011

  View details for PubMedID 17183246

• Cystatin C and measures of physical function in elderly adults - The health, aging, and body composition (HABC) study AMERICAN JOURNAL OF EPIDEMIOLOGY Odden, M. C., Chertow, G. M., Fried, L. F., Newman, A. B., Connelly, S., Angleman, S., Harris, T. B., Simonsick, E. M., Shlipak, M. G. 2006; 164 (12): 1180-1189

  Abstract

  Most studies of the relation between kidney function and physical function have been conducted in persons with advanced kidney disease and have used creatinine-based measures of kidney function. Cystatin C concentration is a measure of kidney function that is independent of muscle mass, unlike creatinine. Using baseline data on 3,043 elderly adults from the Health, Aging, and Body Composition Study (Blacks and Whites recruited from Pittsburgh, Pennsylvania, and Memphis, Tennessee, in 1997-1998), the authors examined the cross-sectional association between cystatin C level and performance on several tests of physical function. After adjustment for demographic and lifestyle variables, chronic health conditions, and inflammation, each standard-deviation (0.34 mg/liter) increase in cystatin C concentration was associated with 1.32 odds (95% confidence interval (CI): 1.20, 1.46) of not completing a 400-m walk, a 10.9-second (95% CI: 8.1, 13.8) slower 400-m walk time, a 0.11-point (95% CI: 0.09, 0.13) reduction in lower extremity performance score, a 1.12-kg (95% CI: 0.83, 1.40) lower grip strength, and a 4.7-nm (95% CI: 3.5, 5.9) lower knee extension strength. In contrast, when kidney function was measured by estimated glomerular filtration rate, the association of kidney function with physical function was only evident below 60 ml/minute/1.73 m2. In these older adults, mild decrements in kidney function, as measured by cystatin C concentration, were associated with poorer physical function.

  View details for DOI 10.1093/aje/kwj333

  View details for Web of Science ID 000242714800006

  View details for PubMedID 17035344

• Renal function and heart failure risk in older black and white individuals - The health, aging, and body composition study ARCHIVES OF INTERNAL MEDICINE Bibbins-Domingo, K., Chertow, G. M., Fried, L. F., Odden, M. C., Newman, A. B., Kritchevsky, S. B., Harris, T. B., Satterfield, S., Cummings, S. R., Shlipak, M. G. 2006; 166 (13): 1396-1402

  Abstract

  Chronic kidney disease is a risk factor for heart failure, an association that may be particularly important in blacks who are disproportionately affected by both processes. Our objective was to determine whether the association of chronic kidney disease with incident heart failure differs between blacks and whites.The study population comprised participants in the Health, Aging, and Body Composition Study without a diagnosis of heart failure (1124 black and 1676 white community-dwelling older persons). The main predictors were quintiles of cystatin C and creatinine concentrations and estimated glomerular filtration rate. The main outcome measure was incident heart failure.Over a mean 5.7 years, 200 participants developed heart failure. High concentrations of cystatin C and low estimated glomerular filtration rate were each associated with heart failure, but the magnitude was greater for blacks than for whites (cystatin C concentration: adjusted hazard ratio for quintile 5 [> or =1.18 mg/dL] vs quintile 1 [<0.84 mg/dL] was 3.0 [95% confidence interval 1.4-6.5] in blacks and 1.4 [95% confidence interval, 0.8-2.5] in whites; estimated glomerular filtration rate: adjusted hazard ratio for quintile 5 (<59.2 mL/min) vs quintile 1 (>86.7 mL/min) was 2.7 [95% confidence interval, 1.4-4.9] in blacks and 1.8 [95% confidence interval, 0.9-3.6] in whites). For cystatin C, this association was observed at more modest decrements in kidney function among blacks as well. The population attributable risk of heart failure was 47% for blacks with moderate or high concentrations of cystatin C (> or =0.94 mg/dL) (56% prevalence) but only 5% among whites (64% prevalence).The association of kidney dysfunction with heart failure appears stronger in blacks than for whites, particularly when cystatin C is used to measure kidney function.

  View details for Web of Science ID 000238916500009

  View details for PubMedID 16832005

• Depression, stress, and quality of life in persons with chronic kidney disease: The Heart and Soul Study NEPHRON CLINICAL PRACTICE Odden, M. C., Whooley, M. A., Shlipak, M. G. 2006; 103 (1): C1–C7

  Abstract

  The effect of mild chronic kidney disease (CKD) on depression, stress, quality of life (QOL), and health status is not well understood. We compared these outcomes in subjects with and without CKD.We performed a cross-sectional study of 967 outpatients enrolled in the Heart and Soul Study. CKD was defined as a measured creatinine clearance < 60 ml/min. Outcome measures included depressive symptoms measured using the Patient Health Questionnaire (PHQ), stress measured using the Perceived Stress Scale (PSS), and QOL and overall health rated as excellent, very good, good, fair, or poor.The prevalence of depressive symptoms (17 vs. 19%, p = 0.4) or perceived stress (11 vs. 16%, p = 0.09) did not vary significantly by CKD. The prevalence of fair or poor QOL was not significantly different in subjects with CKD, compared with those without CKD (24 vs. 23%, p = 0.65). Age-adjusted analyses revealed a significant association of CKD with QOL (p = 0.003), however, this association no longer reached statistical significance after adjustment for confounders (p = 0.06). Subjects with CKD were more likely to report poor or fair overall health than subjects without CKD (42 vs. 34%, p = 0.03). After multivariate adjustment, CKD remained significantly associated with worse overall health (OR = 1.65, 95% CI 1.21-2.24, p = 0.001), and modestly associated with QOL (OR = 1.31, 95% CI 0.99-1.75, p = 0.06), but had no association with depression (p = 0.48) or stress (p = 0.24).In this study of persons with coronary artery disease, subjects with CKD had reduced overall health and modestly reduced QOL; however, mental health was similar in those with and without CKD. These findings suggest that self- assessed overall health may decline at earlier stages of renal dysfunction than mental health outcomes or QOL.

  View details for DOI 10.1159/000090112

  View details for Web of Science ID 000246174100001

  View details for PubMedID 16340237

  View details for PubMedCentralID PMC2776701

• Association of chronic kidney disease and anemia with physical capacity: The heart and soul study JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Odden, M. C., Whooley, M. A., Shlipak, M. G. 2004; 15 (11): 2908–15

  Abstract

  Chronic kidney disease (CKD) and anemia are common conditions in the outpatient setting, but their independent and additive effects on physical capacity have not been well characterized. The association of CKD and anemia with self-reported physical function was evaluated and exercise capacity was measured in patients with coronary disease. A cross-sectional study of 954 outpatients enrolled in the Heart and Soul study was performed. CKD was defined as a measured creatinine clearance <60 ml/min, and anemia was defined as a hemoglobin level of <12g/dl. Physical function was self-assessed using the physical limitation subscale of the Seattle Angina Questionnaire (0 to 100), and exercise capacity was defined as metabolic equivalent tasks achieved at peak exercise. In unadjusted analyses, CKD was associated with lower self-reported physical function (67.6 versus 74.9; P < 0.001) and lower exercise capacity (5.5 versus 7.9; P < 0.001). Similarly, anemia was associated with lower self-reported physical function (62.6 versus 74.3; P < 0.001) and exercise capacity (5.7 versus 7.5; P < 0.001). After multivariate adjustment, CKD (69.4 versus 74.2; P = 0.003) and anemia (67.5 versus 73.6; P = 0.009) each remained associated with lower mean self-reported physical function. In addition, patients with CKD (6.3 versus 7.7; P < 0.001) or anemia (6.5 versus 7.4; P = 0.004) had lower adjusted mean exercise capacities. Participants with both CKD and anemia had lower self-reported physical function and exercise capacity than those with either alone. CKD and anemia are independently associated with physical limitation and reduced exercise capacity in outpatients with coronary disease, and these effects are additive. The broad impact of these disease conditions merits further study.

  View details for DOI 10.1097/01.ASN.0000143743.78092.E3

  View details for Web of Science ID 000224684200016

  View details for PubMedID 15504944

  View details for PubMedCentralID PMC2776664

• Effect of Opuntia ficus indica on symptoms of the alcohol hangover ARCHIVES OF INTERNAL MEDICINE Wiese, J., McPherson, S., Odden, M. C., Shlipak, M. G. 2004; 164 (12): 1334–40

  Abstract

  The severity of the alcohol hangover may be related to inflammation induced by impurities in the alcohol beverage and byproducts of alcohol metabolism. An extract of the Opuntia ficus indica (OFI) plant diminishes the inflammatory response to stressful stimuli.In this double-blind, placebo-controlled, crossover trial, 64 healthy, young adult volunteers were randomly assigned to receive OFI (1600 IU) and identical placebo, given 5 hours before alcohol consumption. During 4 hours, subjects consumed up to 1.75 g of alcohol per kilogram of body weight. Hangover severity (9 symptoms) and overall well-being were assessed on a scale (0-6), and blood and urine samples were obtained the following morning. Two weeks later, the study protocol was repeated with OFI and placebo reversed.Fifty-five subjects completed both the OFI and placebo arms of the study. Three of the 9 symptoms-nausea, dry mouth, and anorexia-were significantly reduced by OFI (all P<.05). Overall, the symptom index was reduced by 2.7 points on average (95% confidence interval, -0.2 to 5.5; P =.07), and the risk of a severe hangover (>/=18 points) was reduced by half (odds ratio, 0.38; 95% confidence interval, 0.16-0.88; P =.02). C-reactive protein levels were strongly associated with hangover severity; the mean symptom index was 4.1 (95% confidence interval, 1.2-7.1; P =.007) higher in subjects with morning C-reactive protein levels greater than 1.0 mg/L. In addition, C-reactive protein levels were 40% higher after subjects consumed placebo compared with OFI.The symptoms of the alcohol hangover are largely due to the activation of inflammation. An extract of the OFI plant has a moderate effect on reducing hangover symptoms, apparently by inhibiting the production of inflammatory mediators.

  View details for DOI 10.1001/archinte.164.12.1334

  View details for Web of Science ID 000222325400011

  View details for PubMedID 15226168

• The relative safety of ephedra compared with other herbal products ANNALS OF INTERNAL MEDICINE Bent, S., Tiedt, T. N., Odden, M. C., Shlipak, M. G. 2003; 138 (6): 468–71

  Abstract

  Ephedra is widely used in dietary supplements that are marketed to promote weight loss or increase energy; however, the safety of this product has been questioned because of numerous case reports of adverse events.To compare the risk for adverse events attributable to ephedra and other herbal products.Comparative case series.American Association of Poison Control Centers Toxic Event Surveillance System Database Annual Report, 2001.The relative risk and 95% confidence interval for experiencing an adverse reaction after ephedra use compared with other herbs. This risk was defined as the ratio of adverse reactions to ephedra versus other products, divided by the ratio of their relative use in the United States.Products containing ephedra accounted for 64% of all adverse reactions to herbs in the United States, yet these products represented only 0.82% of herbal product sales. The relative risks for an adverse reaction in persons using ephedra compared with other herbs were extremely high, ranging from 100 (95% CI, 83 to 140) for kava to 720 (CI, 520 to 1100) for Ginkgo biloba.Ephedra use is associated with a greatly increased risk for adverse reactions compared with other herbs, and its use should be restricted.

  View details for DOI 10.7326/0003-4819-138-6-200303180-00010

  View details for Web of Science ID 000181562400004

  View details for PubMedID 12639079