Caregiving and all-cause mortality in postmenopausal women: Findings from the Women's Health Initiative.

BACKGROUND: Caregiving is commonly undertaken by older women. Research is mixed, however, about the impact of prolonged caregiving on their health, well-being, and mortality risk. Using a prospective study design, we examined the association of caregiving with mortality in a cohort of older women. METHODS: Participants were 158,987 postmenopausal women aged 50-79 years at enrollment into the Women's Health Initiative (WHI) who provided information on current caregiving status and caregiving frequency at baseline (1993-1998) and follow-up (2004-2005). Mortality was ascertained from baseline through March of 2019. Cox regression with caregiving status defined as a time-varying exposure was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for mortality, adjusting for sociodemographic factors, smoking, and history of diabetes, hypertension, cardiovascular disease (CVD), and cancer. Stratified analyses explored whether age, race-ethnicity, depressive symptoms, frequency of caregiving, optimism, and living status modified the association between caregiver status and mortality. RESULTS: At baseline, 40.7% of women (mean age 63.3 years) self-identified as caregivers. During a mean 17.5-year follow-up, all-cause mortality (50,526 deaths) was 9% lower (multivariable-adjusted HR = 0.91, 95% CI: 0.89-0.93) in caregivers compared to non-caregivers. The inverse association between caregiving and all-cause mortality did not differ according to caregiving frequency or when stratified by age, race-ethnicity, depressive symptoms, optimism, or living status (interaction p > 0.05, all). Caregiving was inversely associated with CVD and cancer mortality. CONCLUSION: Among postmenopausal women residing across the United States, caregiving was associated with lower mortality. Studies detailing the type and amount of caregiving are needed to further determine its impact on older women.

Circulating Androgen Concentrations and Risk of Incident Heart Failure in Older Men: The Cardiovascular Health Study.

Background Circulating androgen concentrations in men decline with age and have been linked to diabetes and atherosclerotic cardiovascular disease (ASCVD). A similar relationship has been reported for low total testosterone and incident heart failure (HF) but remains unstudied for free testosterone or the more potent androgen dihydrotestosterone (DHT). We hypothesized that total/free testosterone are inversely related, sex hormone-binding globulin is positively related, and total/free DHT bear a U-shaped relationship with incident HF. Methods and Results In a sample of men from the CHS (Cardiovascular Health Study) without atherosclerotic cardiovascular disease or HF, serum testosterone and DHT concentrations were measured by liquid chromatography-tandem mass spectrometry, and sex hormone-binding globulin by immunoassay. Free testosterone or DHT was calculated from total testosterone or total DHT, sex hormone-binding globulin, and albumin. We used Cox regression to estimate relative risks of HF after adjustment for potential confounders. In 1061 men (aged 76±5 years) followed for a median of 9.6 years, there were 368 HF events. After adjustment, lower calculated free testosterone was significantly associated with higher risk of HF (hazard ratio [HR], 1.14 [95% CI, 1.01-1.28]). Risk estimates for total testosterone (HR, 1.12 [95% CI, 0.99-1.26]), total DHT (HR, 1.10 [95% CI, 0.97-1.24]), calculated free dihydrotestosterone (HR, 1.09 [95% CI, 0.97-1.23]), and sex hormone-binding globulin (HR, 1.07 [95% CI, 0.95-1.21]) were directionally similar but not statistically significant. Conclusions Calculated free testosterone was inversely associated with incident HF, suggesting a contribution of testosterone deficiency to HF incidence among older men. Additional research is necessary to determine whether testosterone replacement therapy might be an effective strategy to lower HF risk in older men.

Body Composition and Incident Heart Failure in Older Adults: Results From 2 Prospective Cohorts.

Background Aging is associated with central fat redistribution and skeletal muscle decline, yet the relationships of tissue compartments with heart failure (HF) remain incompletely characterized. We assessed the contribution of body composition to incident HF in elders. Methods and Results Participants from 2 older cohorts who completed dual-energy X-ray absorptiometry (DEXA) and, in one cohort, computed tomography were included. We evaluated associations with incident HF for DEXA principal components (PCs) and total lean, appendicular lean, total fat and trunk fat mass; and for computed tomography measures of abdominal visceral and subcutaneous fat, thigh muscle, intermuscular fat area and thigh muscle density. DEXA analysis included 3621, and computed tomography analysis 2332 participants. During median follow-up of 11.8 years, 927 participants developed HF. DEXA principal components showed no relationship with HF. After adjustment for height, weight, and cardiovascular risk factors, total lean mass was near significantly associated with higher HF (hazard ratio [HR], 1.25 per SD [1.00-1.56]), whereas total fat mass and thigh muscle density were significantly related to lower HF (HR, 0.82 [0.68-0.99] and HR, 0.87 [0.78-0.97], respectively). Patterns were similar for HF subtypes. The relationships with HF for total lean and fat mass were attenuated after adjusting for intercurrent atrial fibrillation or excluding high natriuretic peptide levels. Conclusions Total lean mass was positively associated, while total fat mass and thigh muscle density were inversely associated, with incident HF. These findings highlight the limitations of DEXA for assessment of HF risk in elders and support the preeminence of computed tomography-measured skeletal muscle quality over mass as a determinant of HF incidence.

Cardiovascular damage phenotypes and all-cause and CVD mortality in older adults.

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 5067 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 probrain 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). CONCLUSIONS: 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.

Associations of Serum Nonesterified Fatty Acids With Coronary Heart Disease Mortality and Nonfatal Myocardial Infarction: The CHS (Cardiovascular Health Study) Cohort.

Background Significant associations have been reported between serum total nonesterified fatty acid (NEFA) concentrations and coronary heart disease (CHD) mortality and incident nonfatal myocardial infarction (MI) in some prospective cohort studies. Little is known about whether individual or subclasses (saturated, polyunsaturated [n-6 and n-3], and trans fatty acids) of serum NEFAs relate to CHD mortality and nonfatal MI. Methods and Results CHS (Cardiovascular Health Study) participants (N=1681) who had no history of MI, angina, or revascularization or were free of MI at baseline (1996-1997) were included. NEFAs were quantified using gas chromatography. Cox regression analysis was used to evaluate associations of 5 subclasses and individual NEFAs with CHD composite (CHD mortality and nonfatal MI), CHD mortality, and incident nonfatal MI. During a median follow-up of 11.7 years, 266 cases of CHD death and 271 cases of nonfatal MI occurred. In the fully adjusted model, no significant associations were identified between individual NEFA and CHD composite. Exploratory analyses indicated that lauric acid (12:0) was negatively associated (hazard ratio [HR], 0.76; 95% CI, 0.59-0.98; P=0.0328) and dihomo-γ-linolenic acid (20:3n-6) was positively associated with CHD mortality (HR, 1.34; 95% CI, 1.02-1.76; P=0.0351). Elaidic acid (18:1n-7t) was positively associated with incident nonfatal MI (HR, 1.46; 95% CI, 1.01-2.12; P=0.0445). No significant associations were observed for NEFA subclass and any outcomes. Conclusions In CHS participants, 2 NEFAs, dihomo-γ-linolenic and elaidic acids, were positively associated with CHD mortality and nonfatal MI, respectively, suggesting potential susceptibility biomarkers for risks of CHD mortality and nonfatal MI.

The association of prediagnosis social support with survival after heart failure in the Cardiovascular Health Study.

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.

Trends in Blood Pressure and High-Sensitivity Cardiac Troponin-T With Cardiovascular Disease: The Cardiovascular Health Study.

BACKGROUND: High-sensitivity cardiac troponin T (hs-cTnT) is individually associated with incident hypertension (HTN) and cardiovascular disease (CVD) events. We hypothesize that the increases in hs-cTnT with increases in blood pressure will be related to higher incidence of CVD. METHODS: The Cardiovascular Health Study is a longitudinal cohort of older adults. Those with hs-cTnT data and CVD risk factors at baseline and follow-up (2-3 years later) were stratified based on systolic blood pressure (SBP; optimal: <120 mm Hg, intermediate: 120-139 mm Hg, elevated: ≥140 mm Hg) and hs-cTnT (undetectable: <5 ng/l, detectable: 5-13 ng/l, elevated: ≥14 ng/l) categories. SBP and hs-cTnT were classified as increased or decreased if they changed categories between exams, and stable if they did not. Cox regression evaluated incident CVD events over an average 9-year follow-up. RESULTS: Among 2,219 adults, 510 (23.0 %) had decreased hs-cTnT, 1,279 (57.6 %) had stable hs-cTnT, and 430 (19.4 %) had increased hs-cTnT. Those with increased hs-cTnT had a higher CVD risk with stable SBP (hazard ratio [HR]: 1.28 [1.04-1.57], P = 0.02) or decreased SBP (HR: 1.57 [1.08-2.28], P = 0.02) compared to those within the same SBP group but a stable hs-cTnT. In those with lower SBP at follow-up, there was an inverse relation between diastolic blood pressure (DBP) and risk of CVD events in those with increased hs-cTnT (HR: 0.44 per 10 mm Hg increase, P < 0.01). CONCLUSION: An increase in hs-cTnT over time is associated with a higher risk of CVD even when the blood pressure is stable or decreases over time.

Association of Biomarker and Physiologic Indices With Mortality in Older Adults: Cardiovascular Health Study.

Background: A goal of gerontology is discovering aging phenotypes that reflect biological aging distinct from disease pathogenesis. Biomarkers that strongly and independently associated with mortality and that statistically attenuated chronologic age could be used to define such a phenotype. We determined the association of a Biomarker Index (BI) with mortality and compared it with a validated Physiologic Index (PI) in older adults. Methods: The indices were constructed in the Cardiovascular Health Study, mean (SD) age 74.5 (5.1) years. The BI incorporated circulating levels of new biomarkers, including insulin-like growth factor-1, insulin-like growth factor-binding protein 3, amino-terminal pro-B-type natriuretic peptide, dehydroepiandrosterone sulfate, and interleukin-6, and was built in test (N = 2,197) and validation (N = 1,124) samples. The PI included carotid intima-media thickness, pulmonary capacity, brain white matter grade, cystatin-C, and fasting glucose. Multivariable Cox proportional hazards models predicting death were calculated with 10 years of follow-up. Results: In separate age-adjusted models, the hazard ratio for mortality per point of the BI was 1.30 (95% confidence interval 1.25, 1.34) and the BI attenuated age by 25%. The hazard ratio for the PI was 1.28 (1.24, 1.33; 29% age attenuation). In the same model, the hazard ratio for the BI was 1.23 (1.18, 1.28) and for the PI was 1.22 (1.17, 1.26), and age was attenuated 42.5%. Associations persisted after further adjustment. Conclusions: The BI and PI were significantly and independently associated with mortality. Both attenuated the age effect on mortality substantially. The indices may be feasible phenotypes for developing interventions hoping to alter the trajectory of aging.

Cerebrovascular Steal Phenomenon and Electroconvulsive Therapy: A Case Report and Review of the Literature.

Electroconvulsive therapy (ECT) is a safe and effective treatment for major depressive disorder, but cerebrovascular and cardiovascular complications, although rare, remain the most concerning. This is particularly notable in those with preexisting cerebrovascular disease, which impacts dynamic cerebral autoregulation. In these patients, the increased blood flow to the seizing portions of the brain induced by ECT potentially can reduce cerebral blood flow to ischemic areas, possibly causing adverse neurological events. The authors describe a patient with chronic cerebral ischemic disease, chronic anemia, and major depressive disorder undergoing ECT to achieve remission. The patient developed recurrent focal neurological deficits after each ECT procedure, with neurological recovery within 48 hours post-ECT. Clinical guidelines may need to be updated for the management of ECT patients with cerebrovascular disease who may be at an increased risk of intraictal and possibly postictal regional ischemia, especially in areas already compromised by a prior stroke and/or by reduced cerebral oxygenation caused by symptomatic anemia at risk of ischemia. Research is needed to assess changes in regional cerebral blood flow during and after ECT in patients with cerebrovascular disease, including small-vessel cerebral ischemia, and to evaluate these changes in relation to the location, intensity, and duration of induced seizure.

Comparing methods to address bias in observational data: statin use and cardiovascular events in a US cohort.

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Emergency Department Pain Management Following Implementation of a Geriatric Hip Fracture Program.

INTRODUCTION: Over 300,000 patients in the United States sustain low-trauma fragility hip fractures annually. Multidisciplinary geriatric fracture programs (GFP) including early, multimodal pain management reduce morbidity and mortality. Our overall goal was to determine the effects of a GFP on the emergency department (ED) pain management of geriatric fragility hip fractures. METHODS: We performed a retrospective study including patients age ≥65 years with fragility hip fractures two years before and two years after the implementation of the GFP. Outcomes were time to (any) first analgesic, use of acetaminophen and fascia iliaca compartment block (FICB) in the ED, and amount of opioid medication administered in the first 24 hours. We used permutation tests to evaluate differences in ED pain management following GFP implementation. RESULTS: We studied 131 patients in the pre-GFP period and 177 patients in the post-GFP period. In the post-GFP period, more patients received FICB (6% vs. 60%; difference 54%, 95% confidence interval [CI] 45-63%; p<0.001) and acetaminophen (10% vs. 51%; difference 41%, 95% CI 32-51%; p<0.001) in the ED. Patients in the post-GFP period also had a shorter time to first analgesic (103 vs. 93 minutes; p=0.04) and received fewer morphine equivalents in the first 24 hours (15mg vs. 10mg, p<0.001) than patients in the pre-GFP period. CONCLUSION: Implementation of a GFP was associated with improved ED pain management for geriatric patients with fragility hip fractures. Future studies should evaluate the effects of these changes in pain management on longer-term outcomes.

Risk Factors for Incident Carotid Artery Revascularization among Older Adults: The Cardiovascular Health Study.

BACKGROUND: Population-based risk factors for carotid artery revascularization are not known. We investigated the association between demographic and clinical characteristics and incident carotid artery revascularization in a cohort of older adults. METHODS: Among Cardiovascular Health Study participants, a population-based cohort of 5,888 adults aged 65 years or older enrolled in two waves (1989-1990 and 1992-1993), 5,107 participants without a prior history of carotid endarterectomy (CEA) or cerebrovascular disease had a carotid ultrasound at baseline and were included in these analyses. Cox proportional hazards multivariable analysis was used to determine independent risk factors for incident carotid artery revascularization. RESULTS: Over a mean follow-up of 13.5 years, 141 participants underwent carotid artery revascularization, 97% were CEA. Baseline degree of stenosis and incident ischemic cerebral events occurring during follow-up were the strongest predictors of incident revascularization. After adjustment for these, factors independently associated with an increased risk of incident revascularization were: hypertension (HR 1.53; 95% CI: 1.05-2.23), peripheral arterial disease (HR 2.57; 95% CI: 1.34-4.93), and low-density lipoprotein cholesterol (HR 1.23 per standard deviation [SD] increment [35.4 mg/dL]; 95% CI: 1.04-1.46). Factors independently associated with a lower risk of incident revascularization were: female gender (HR 0.51; 95% CI: 0.34-0.77) and older age (HR 0.69 per SD increment [5.5 years]; 95% CI: 0.56-0.86). CONCLUSIONS: Even after accounting for carotid stenosis and incident cerebral ischemic events, carotid revascularization is related to age, gender, and cardiovascular risk factors. Further study of these demographic disparities and the role of risk factor control is warranted.

Effects of Disease Burden and Functional Adaptation on Morbidity and Mortality on Older Adults.

OBJECTIVES: To ascertain whether older adults with extensive disease but relative vigor (adapters) shorten the period at the end of life in which they live with morbidity (compress morbidity). DESIGN: Prospective, community-based cohort study in four U.S. cities. SETTING: Cardiovascular Health Study. PARTICIPANTS: Individuals aged 65 and older. MEASUREMENTS: Participants were categorized into three groups according to extent of disease (assessed noninvasively), vigor, and frailty (expected agers (n = 3,528, extent of disease similar to vigor and frailty-reference group), adapters (n = 882, higher disease but vigorous), and prematurely frail (n = 855, lower disease but frail)) and compared according to years of able life (YAL), years of self-reported healthy life (YHL), and mortality using multivariable regression and survival analysis. RESULTS: After adjustment, adapters had 0.97 (95% confidence interval (CI) = 0.60-1.33) more YAL and 0.54 (95% CI = 0.19-0.90) more YHL than expected agers, and those who were prematurely frail had -0.99 (95% CI = -1.36 to -0.62) fewer YAL and -0.53 (95% CI = -0.89 to -0.17) fewer YHL than expected agers. Adapters had 0.9 more and prematurely frail had 1.5 fewer years of total life than expected agers (P < .001). Adapters spent 55% of their remaining life able and healthy, those who were prematurely frail spent 37%, and of expected agers spent 47% (P < .001). CONCLUSION: Despite similar levels of disease burden, older adults who were more vigorous appeared to compress morbidity and live longer. Older adults with higher frailty lengthened morbidity and had greater mortality. Adaptive factors may compress morbidity and decrease mortality.

Cardiovascular Disease, Mortality Risk, and Healthcare Costs by Lipoprotein(a) Levels According to Low-density Lipoprotein Cholesterol Levels in Older High-risk Adults.

BACKGROUND: The value of lipoprotein(a) (Lp[a]) for predicting cardiovascular disease (CVD) across low-density lipoprotein cholesterol (LDL-C) is uncertain. HYPOTHESIS: In older high-risk adults, higher LDL and Lp(a) combined would be associated with higher CVD risk and more healthcare costs. METHODS: We included 3251 high-risk subjects (prior CVD, diabetes, or 10-year Framingham CVD risk >20%) age ≥65 years from the Cardiovascular Health Study and examined the relation of Lp(a) tertiles with incident CVD, coronary heart disease (CHD), and all-cause mortality within LDL-C strata (spanning <70 mg/dL to ≥160 mg/dL). We also examined 1-year all-cause and CVD healthcare costs from Medicare claims. RESULTS: Over a 22.5-year follow-up, higher Lp(a) levels predicted CVD and total mortality (both standardized hazard ratio [HR]: 1.06, P < 0.01), whereas higher LDL-C levels predicted higher CHD (standardized HR: 1.09, P < 0.01) but lower total mortality (standardized HR: 0.94, P < 0.001). Adjusted HRs in the highest (vs lowest) tertile of Lp(a) level were 1.95 (P = 0.06) for CVD events and 2.68 (P = 0.03) for CHD events when LDL-C was <70 mg/dL. One-year all-cause healthcare costs were increased for Lp(a) ($771 per SD of 56 µg/mL [P = 0.03], $1976 for Lp(a) 25-64 µg/mL vs <25 µg/mL [P = 0.02], and $1648 for Lp(a) ≥65 µg/mL vs <25 µg/mL [P = 0.054]) but not LDL-C. CONCLUSIONS: In older high-risk adults, increased Lp(a) levels were associated with higher CVD risk, especially in those with LDL-C <70 mg/dL, and with higher healthcare costs.

Incident Atrial Fibrillation and Disability-Free Survival in the Cardiovascular Health Study.

OBJECTIVES: To assess the associations between incident atrial fibrillation (AF) and disability-free survival and risk of disability. DESIGN: Prospective cohort study. SETTING: Cardiovascular Health Study. PARTICIPANTS: 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. MEASUREMENTS: 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. RESULTS: 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. CONCLUSION: These results suggest that AF is a risk factor for shorter functional longevity in older adults, independent of other risk factors and comorbid conditions.

Predicting Future Years of Life, Health, and Functional Ability: A Healthy Life Calculator for Older Adults.

Objective: To create personalized estimates of future health and ability status for older adults. Method: Data came from the Cardiovascular Health Study (CHS), a large longitudinal study. Outcomes included years of life, years of healthy life (based on self-rated health), years of able life (based on activities of daily living), and years of healthy and able life. We developed regression estimates using the demographic and health characteristics that best predicted the four outcomes. Internal and external validity were assessed. Results: A prediction equation based on 11 variables accounted for about 40% of the variability for each outcome. Internal validity was excellent, and external validity was satisfactory. The resulting CHS Healthy Life Calculator (CHSHLC) is available at http://healthylifecalculator.org. Conclusion: CHSHLC provides a well-documented estimate of future years of healthy and able life for older adults, who may use it in planning for the future.

Multisystem physiologic impairments and changes in gait speed of older adults.

BACKGROUND: Slowed gait is an important health indicator in older adults but a single identifiable cause is often lacking. We assessed whether a summary index measuring impairments across multiple physiologic systems was associated with slowed gait in older individuals. METHODS: Data from the Cardiovascular Health Study (n = 3,010) were used to assess associations between baseline physiologic index (measuring vasculature, brain, kidneys, lungs, and glucose metabolism; range 0-10 with 0-2 points/system and lower score indicating higher function) and annual gait speed (m/s) over 6 years. Participants with complete data on the physiologic index and at least two gait speed measures were included. Mean gait speed and 95% confidence intervals (CI) by category of index were calculated using mixed effects models. RESULTS: Those with scores of three or higher on the index had significantly slower gait speed at baseline compared to those with scores of 0-2 (7-10: mean speed = 0.83 m/s, 95% CI: 0.80, 0.84; 0-2: mean speed = 1.01 m/s, 95% CI: 0.99, 1.03). Those with higher indices also had faster decline in gait speed compared to those with lower scores after adjustment for demographic and health characteristics (7-10: change in speed = -0.020 m/s/year, 95% CI: -0.024, -0.016; 0-2: change in speed= -0.010 m/s/year, 95% CI: -0.014, -0.006). CONCLUSIONS: Greater impairment across five organ systems was associated with slower gait speed and greater declines in gait speed over 6 years. Impairments accumulated over multiple physiologic systems may make older adults more vulnerable to slow gait speed.

Testosterone, dihydrotestosterone, and incident cardiovascular disease and mortality in the cardiovascular health study.

CONTEXT: Low testosterone (T) is associated with prevalent cardiovascular disease (CVD) and mortality. DHT, a more potent androgen, may also be associated with CVD and mortality, but few studies have examined this. OBJECTIVE: The study objective was to examine whether T and DHT are risk factors for incident CVD and mortality. DESIGN: In a longitudinal cohort study, we evaluated whether total T, calculated free T (cFT), DHT, and calculated free DHT were associated with incident CVD and mortality in men in the Cardiovascular Health Study (mean age 76, range 66-97 years) who were free of CVD at the time of blood collection. MAIN OUTCOME: The main outcomes were incident CVD and all-cause mortality. RESULTS: Among 1032 men followed for a median of 9 years, 436 incident CVD events and 777 deaths occurred. In models adjusted for cardiovascular risk factors, total T and cFT were not associated with incident CVD or all-cause mortality, whereas DHT and calculated free DHT had curvilinear associations with incident CVD (P < .002 and P = .04, respectively) and all-cause mortality (P < .001 for both). CONCLUSIONS: In a cohort of elderly men, DHT and calculated free DHT were associated with incident CVD and all-cause mortality. Further studies are needed to confirm these results and to clarify the underlying physiologic mechanisms.

Testosterone and dihydrotestosterone and incident ischaemic stroke in men in the Cardiovascular Health Study.

OBJECTIVE: Ischaemic stroke is a major cause of morbidity and mortality in elderly men. Our main objective was to examine whether testosterone (T) or dihydrotestosterone (DHT) was associated with incident ischaemic stroke in elderly men. DESIGN: Cohort study. PARTICIPANTS: Elderly men in the Cardiovascular Health Study who had no history of stroke, heart disease or prostate cancer as of 1994 and were followed until December 2010. MEASUREMENTS: Adjudicated ischaemic stroke. RESULTS: Among 1032 men (mean age 76, range 66-97), followed for a median of 10 years, 114 had an incident ischaemic stroke. Total T and free T were not significantly associated with stroke risk, while DHT had a nonlinear association with incident stroke (P = 0·006) in analyses adjusted for stroke risk factors. The lowest risk of stroke was at DHT levels of 50-75 ng/dl, with greater risk of stroke at DHT levels above 75 ng/dl or below 50 ng/dl. Results were unchanged when SHBG was added to the model. Calculated free DHT had an inverse linear association with incident ischaemic stroke with HR 0·77 (95% CI, 0·61, 0·98) per standard deviation in analyses adjusted for stroke risk factors. CONCLUSIONS: Dihydrotestosterone had a nonlinear association with stroke risk in which there was an optimal DHT level associated with the lowest stroke risk. Further studies are needed to confirm these results and to clarify whether there is an optimal androgen range associated with the least risk of adverse outcomes in elderly men.