Stephen B. Kritchevsky

Gait Speed and Survival in Older Adults

CONTEXT Survival estimates help individualize goals of care for geriatric patients, but life tables fail to account for the great variability in survival. Physical performance measures, such as gait speed, might help account for variability, allowing clinicians to make more individualized estimates. OBJECTIVE To evaluate the relationship between gait speed and survival. DESIGN, SETTING, AND PARTICIPANTS Pooled analysis of 9 cohort studies (collected between 1986 and 2000), using individual data from 34,485 community-dwelling older adults aged 65 years or older with baseline gait speed data, followed up for 6 to 21 years. Participants were a mean (SD) age of 73.5 (5.9) years; 59.6%, women; and 79.8%, white; and had a mean (SD) gait speed of 0.92 (0.27) m/s. MAIN OUTCOME MEASURES Survival rates and life expectancy. RESULTS There were 17,528 deaths; the overall 5-year survival rate was 84.8% (confidence interval [CI], 79.6%-88.8%) and 10-year survival rate was 59.7% (95% CI, 46.5%-70.6%). Gait speed was associated with survival in all studies (pooled hazard ratio per 0.1 m/s, 0.88; 95% CI, 0.87-0.90; P < .001). Survival increased across the full range of gait speeds, with significant increments per 0.1 m/s. At age 75, predicted 10-year survival across the range of gait speeds ranged from 19% to 87% in men and from 35% to 91% in women. Predicted survival based on age, sex, and gait speed was as accurate as predicted based on age, sex, use of mobility aids, and self-reported function or as age, sex, chronic conditions, smoking history, blood pressure, body mass index, and hospitalization. CONCLUSION In this pooled analysis of individual data from 9 selected cohorts, gait speed was associated with survival in older adults.

Elevated Aortic Pulse Wave Velocity, a Marker of Arterial Stiffness, Predicts Cardiovascular Events in Well-Functioning Older Adults

Background—Aging results in vascular stiffening and an increase in the velocity of the pressure wave as it travels down the aorta. Increased aortic pulse wave velocity (aPWV) has been associated with mortality in clinical but not general populations. The objective of this investigation was to determine whether aPWV is associated with total and cardiovascular (CV) mortality and CV events in a community-dwelling sample of older adults. Methods and Results—aPWV was measured at baseline in 2488 participants from the Health, Aging and Body Composition (Health ABC) study. Vital status, cause of death and coronary heart disease (CHD), stroke, and congestive heart failure were determined from medical records. Over 4.6 years, 265 deaths occurred, 111 as a result of cardiovascular causes. There were 341 CHD events, 94 stroke events, and 181 cases of congestive heart failure. Results are presented by quartiles because of a threshold effect between the first and second aPWV quartiles. Higher aPWV was associated with both total mortality (relative risk, 1.5, 1.6, and 1.7 for aPWV quartiles 2, 3, and 4 versus 1; P=0.019) and cardiovascular mortality (relative risk, 2.1, 3.0, and 2.3 for quartiles 2, 3, and 4 versus 1; P=0.004). aPWV quartile was also significantly associated with CHD (P=0.007) and stroke (P=0.001). These associations remained after adjustment for age, gender, race, systolic blood pressure, known CV disease, and other variables related to events. Conclusions—Among generally healthy, community-dwelling older adults, aPWV, a marker of arterial stiffness, is associated with higher CV mortality, CHD, and stroke.

Inflammatory Markers and Onset of Cardiovascular Events Results From the Health ABC Study

Background—Inflammation plays an important role in cardiovascular disease. The aim of this study is to investigate the predictive value of several inflammatory markers on the incidence of cardiovascular events in well-functioning older persons. Methods and Results—The subjects were 2225 participants 70 to 79 years old, without baseline cardiovascular disease, who were enrolled in the Health, Aging, and Body Composition study. Incident coronary heart disease (CHD), stroke, and congestive heart failure (CHF) events were detected during an average follow-up of 3.6 years. Blood levels of interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-&agr; (TNF-&agr;) were assessed. After adjustment for potential confounders, IL-6 was significantly associated with all outcomes (CHD events, per IL-6 SD increase: RR, 1.27; 95% CI, 1.10 to 1.48; stroke events, per IL-6 SD increase: RR, 1.45; 95% CI, 1.12 to 1.86; CHF events, per IL-6 SD increase: RR, 1.72; 95% CI, 1.40 to 2.12). TNF-&agr; showed significant associations with CHD (per TNF-&agr; SD increase: RR, 1.22; 95% CI, 1.04 to 1.43) and CHF (per TNF-&agr; SD increase: RR, 1.59; 95% CI, 1.30 to 1.95) events. CRP was significantly associated with CHF events (per CRP SD increase: RR, 1.48; 95% CI, 1.23 to 1.78). A composite summary indicator of inflammation showed a strong association with incident cardiovascular events, with an especially high risk if all 3 inflammatory markers were in the highest tertile. Conclusions—Findings suggest that inflammatory markers are independent predictors of cardiovascular events in older persons.

Common genetic determinants of vitamin D insufficiency: a genome-wide association study

BACKGROUND Vitamin D is crucial for maintenance of musculoskeletal health, and might also have a role in extraskeletal tissues. Determinants of circulating 25-hydroxyvitamin D concentrations include sun exposure and diet, but high heritability suggests that genetic factors could also play a part. We aimed to identify common genetic variants affecting vitamin D concentrations and risk of insufficiency. METHODS We undertook a genome-wide association study of 25-hydroxyvitamin D concentrations in 33 996 individuals of European descent from 15 cohorts. Five epidemiological cohorts were designated as discovery cohorts (n=16 125), five as in-silico replication cohorts (n=9367), and five as de-novo replication cohorts (n=8504). 25-hydroxyvitamin D concentrations were measured by radioimmunoassay, chemiluminescent assay, ELISA, or mass spectrometry. Vitamin D insufficiency was defined as concentrations lower than 75 nmol/L or 50 nmol/L. We combined results of genome-wide analyses across cohorts using Z-score-weighted meta-analysis. Genotype scores were constructed for confirmed variants. FINDINGS Variants at three loci reached genome-wide significance in discovery cohorts for association with 25-hydroxyvitamin D concentrations, and were confirmed in replication cohorts: 4p12 (overall p=1.9x10(-109) for rs2282679, in GC); 11q12 (p=2.1x10(-27) for rs12785878, near DHCR7); and 11p15 (p=3.3x10(-20) for rs10741657, near CYP2R1). Variants at an additional locus (20q13, CYP24A1) were genome-wide significant in the pooled sample (p=6.0x10(-10) for rs6013897). Participants with a genotype score (combining the three confirmed variants) in the highest quartile were at increased risk of having 25-hydroxyvitamin D concentrations lower than 75 nmol/L (OR 2.47, 95% CI 2.20-2.78, p=2.3x10(-48)) or lower than 50 nmol/L (1.92, 1.70-2.16, p=1.0x10(-26)) compared with those in the lowest quartile. INTERPRETATION Variants near genes involved in cholesterol synthesis, hydroxylation, and vitamin D transport affect vitamin D status. Genetic variation at these loci identifies individuals who have substantially raised risk of vitamin D insufficiency. FUNDING Full funding sources listed at end of paper (see Acknowledgments).

Prognostic Value of Usual Gait Speed in Well-Functioning Older People—Results from the Health, Aging and Body Composition Study

Objectives: To define clinically relevant cutpoints for usual gait speed and to investigate their predictive value for health‐related events in older persons.

Leg Muscle Mass and Composition in Relation to Lower Extremity Performance in Men and Women Aged 70 to 79: The Health, Aging and Body Composition Study

OBJECTIVES: The loss of muscle mass with aging, or sarcopenia, is hypothesized to be associated with the deterioration of physical function. Our aim was to determine whether low leg muscle mass and greater fat infiltration in the muscle were associated with poor lower extremity performance (LEP).

Sarcopenia: Alternative Definitions and Associations with Lower Extremity Function

Objectives: To compare two sarcopenia definitions and examine the relationship between them and lower extrem‐ity function and other health related factors using data from the baseline examination of the Health Aging and Body Composition (Health ABC) Study.

Sarcopenic obesity: definition, cause and consequences.

Purpose of reviewOlder obese persons with decreased muscle mass or strength are at special risk for adverse outcomes. We discuss potential pathways to muscle impairment in obese individuals and the consequences that joint obesity and muscle impairment may have on health and disability. Tantamount to this discussion is whether low muscle mass or, rather, muscle weakness should be used for the definition. Recent findingsExcess energy intake, physical inactivity, low-grade inflammation, insulin resistance and changes in hormonal milieu may lead to the development of so-called ‘sarcopenic obesity’. It was originally believed that the culprit of age-related muscle weakness was a reduction in muscle mass, but it is now clear that changes in muscle composition and quality are predominant. We propose that the risk of adverse outcomes, such as functional limitation and mortality, is better estimated by considering jointly obesity and muscle strength rather than obesity and muscle mass and the term ‘sarcopenic obesity’ should be revisited. SummaryRecognition of obese patients who have associated muscle problems is an essential goal for clinicians. Further research is needed to identify new target for prevention and cure of this important geriatric syndrome.

Effect of Structured Physical Activity on Prevention of Major Mobility Disability in Older Adults: The LIFE Study Randomized Clinical Trial

IMPORTANCE In older adults reduced mobility is common and is an independent risk factor for morbidity, hospitalization, disability, and mortality. Limited evidence suggests that physical activity may help prevent mobility disability; however, there are no definitive clinical trials examining whether physical activity prevents or delays mobility disability. OBJECTIVE To test the hypothesis that a long-term structured physical activity program is more effective than a health education program (also referred to as a successful aging program) in reducing the risk of major mobility disability. DESIGN, SETTING, AND PARTICIPANTS The Lifestyle Interventions and Independence for Elders (LIFE) study was a multicenter, randomized trial that enrolled participants between February 2010 and December 2011, who participated for an average of 2.6 years. Follow-up ended in December 2013. Outcome assessors were blinded to the intervention assignment. Participants were recruited from urban, suburban, and rural communities at 8 centers throughout the United States. We randomized a volunteer sample of 1635 sedentary men and women aged 70 to 89 years who had physical limitations, defined as a score on the Short Physical Performance Battery of 9 or below, but were able to walk 400 m. INTERVENTIONS Participants were randomized to a structured, moderate-intensity physical activity program (n = 818) conducted in a center (twice/wk) and at home (3-4 times/wk) that included aerobic, resistance, and flexibility training activities or to a health education program (n = 817) consisting of workshops on topics relevant to older adults and upper extremity stretching exercises. MAIN OUTCOMES AND MEASURES The primary outcome was major mobility disability objectively defined by loss of ability to walk 400 m. RESULTS Incident major mobility disability occurred in 30.1% (246 participants) of the physical activity group and 35.5% (290 participants) of the health education group (hazard ratio [HR], 0.82 [95% CI, 0.69-0.98], P = .03).Persistent mobility disability was experienced by 120 participants (14.7%) in the physical activity group and 162 participants (19.8%) in the health education group (HR, 0.72 [95% CI, 0.57-0.91]; P = .006). Serious adverse events were reported by 404 participants (49.4%) in the physical activity group and 373 participants (45.7%) in the health education group (risk ratio, 1.08 [95% CI, 0.98-1.20]). CONCLUSIONS AND RELEVANCE A structured, moderate-intensity physical activity program compared with a health education program reduced major mobility disability over 2.6 years among older adults at risk for disability. These findings suggest mobility benefit from such a program in vulnerable older adults. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01072500.

Inflammatory Markers and Depressed Mood in Older Persons: Results from the Health, Aging and Body Composition Study

Patients with major depression have elevated levels of inflammatory cytokines. We examined the link between inflammatory markers and depressed mood in a community-based sample of older people. Data are from 3024 well-functioning older persons, 70-79 years of age, participating in the Health, Aging and Body Composition study. Depressed mood was defined as a Center for Epidemiologic Studies Depression scale score of 16 or higher. Plasma concentrations of interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and C-reactive protein (CRP) were measured. Compared with the 2879 nondepressed subjects, the 145 persons with depressed mood had higher median plasma levels of IL-6 (2.04 vs. 1.83 pg/mL, p =.02), TNF-alpha (3.43 vs. 3.16 pg/mL, p =.05), and CRP (1.96 vs. 1.66 mg/L, p =.03). After adjustment for health and demographic variables, depressed mood was especially prevalent among persons who had a high (above median) plasma level for at least two of the inflammatory markers. Compared with those without high levels, for persons with a high level for two or all three markers the risk of depressed mood was 2.45 (95% confidence interval [CI] = 1.34-4.47) and 2.40 (95% CI = 1.27-4.53), respectively. The association between depressed mood and serum level of IL-6 was significantly stronger in men than in women. In old age, depressed mood is associated with high levels of inflammatory markers, suggesting that depressed mood is causing and/or caused by systemic inflammation.