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
Abstract BACKGROUND 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. METHODS 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). RESULTS 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). CONCLUSIONS 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.
Background: The timed 25-foot walk (T25FW) is a key clinical outcome measure in multiple sclerosis patient management and clinical research. Objectives: To evaluate T25FW performance and factors associated with its change in the Multiple Sclerosis Outcome Assessments Consortium (MSOAC) Placebo Database ( n = 2465). Methods: 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. Results: 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. Conclusion: 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.
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.
Objectives To examine the association between kidney function and all‐cause mortality in octogenarians. Design Retrospective analysis of prospectively collected data. Setting Community. Participants Serum creatinine and cystatin C were measured in 1,053 Cardiovascular Health Study ( CHS ) All Stars participants. Measurements Estimated glomerular filtration rate (e GFR ) was determined using the Chronic Kidney Disease Epidemiology Collaboration creatinine (e GFR CR ) and cystatin C one‐variable (e GFR CYS ) equations. The association between quintiles of kidney function and all‐cause mortality was analyzed using unadjusted and adjusted Cox proportional hazards models. Results 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 e GFR 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 e GFR 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 e GFR CYS and all‐cause mortality was linear in those with e GFR CYS of less than 60 mL/min per 1.73 m 2 , and in the multivariate analyses, the lowest quintile of e GFR 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 ). Conclusion Moderate reduction in kidney function is a risk factor for all‐cause mortality in octogenarians. The association between e GFR CR and all‐cause mortality differed from that observed with e GFR CYS ; the relationship was U‐shaped for e GFR CR , whereas the risk was primarily present in the lowest quintile for e GFR CYS .
ABSTRACT Objective Behavioral risk factors for dementia tend to co-occur and interrelate, especially poor diet, physical inactivity, sleep disturbances, and depression. Having multiple of these modifiable behavioral risk factors (MBRFs) may predict a particularly shortened cognitive health span and therefore may signal high-risk status/high intervention need. Methods These secondary analyses of data from the Cardiovascular Health Study included 3149 participants aged 65 to 74 years (mean [standard deviation {SD}] age = 69.5 [2.5] years; 59.6% female). MBRF exposures were self-reports regarding a) diet, b) activity, c) sleep, and d) depression symptoms. We primarily analyzed MBRF counts. For up to 26 years of follow-up, we assessed the a) number of remaining cognitively healthy life-years (CHLYs) and b) 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 report indicating significant cognitive decline, or dementia medication use. Results Participants averaged a remaining 16 LYs (SD = 7 LYs), 12.2 CHLYs (SD = 6.6 CHLYs), and 78.1% of LYs being CHLYs (SD = 25.6 CHLYs). 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 to 3 fewer LYs and CHLYs as well as about 6% lower %CHLY (95% confidence interval = −9.0 to −2.5 %CHLYs; p = .001). Conclusions MBRF-related reductions in the cognitive health span 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.
BACKGROUND: Social influencers of health namely race ethnicity, and structural inequities are known to affect the incidence of out of hospital sudden death (OHSD).We sought to examine the association between social influencers of health and the incidence of OHSD in the diverse neighborhoods of New York City during the first wave of coronavirus disease 2019 (COVID-19) epidemic. METHODS:New York City ZIP-stratified data on OHSD were obtained from the Fire Department of New York during the first wave of COVID-19 epidemic (March 1 to April 10, 2019) and the same period in 2020.To assess associates of OHSD, ZIP code-specific sociodemographic characteristics for 8 491 238 New York City residents were obtained via the US Census Bureau's 2018 American Community Survey and the New York Police Department's crime statistics. RESULTS:Between March 1 and April 10, 2020, the number of OHSD rose to 4334 from 1112 compared with the year prior.Of the univariate ZIP code level variables evaluated, proportions of Black race, Hispanic/Latino ethnicity, single parent household, unemployed inhabitants, people completing less than high school education, inhabitants with no health insurance, people financially struggling or living in poverty, percent of noncitizens, and population density were associated with increased rates of OHSD within ZIP codes.In multivariable analysis, ZIP codes with higher proportions of inhabitants with less than high school education (P<0.001) and higher proportions of Black race (P=0.04) were independent predictors for increases in ZIP code rates of OHSD. CONCLUSIONS:Educational attainment and the proportion of Black race in New York City ZIP codes remained independent predictors of increased rates of ZIP code level OHSD during the COVID-19 outbreak even after controlling for 2019 rates.To facilitate health equity, future research should focus on characterizing the impacts of structural inequities while exploring strategies to mitigate their effects.
