Susan M. Rubin

Hormone Therapy To Prevent Disease and Prolong Life in Postmenopausal Women

Abstract ▪Purpose:To critically review the risks and benefits of hormone therapy for asymptomatic postmenopausal women who are considering long-term hormone therapy to prevent disease or to prolong...

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.

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.

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.

Inflammatory markers and cognition in well-functioning African-American and white elders

Background: Several lines of evidence suggest that inflammatory mechanisms contribute to AD. Objective: To examine whether several markers of inflammation are associated with cognitive decline in African-American and white well-functioning elders. Methods: The authors studied 3,031 African-American and white men and women (mean age 74 years) enrolled in the Health, Aging, and Body Composition Study. Serum levels of interleukin-6 (IL-6) and C-reactive protein (CRP) and plasma levels of tumor necrosis factor-α (TNFα) were measured at baseline; cognition was assessed with the Modified Mini-Mental State Examination (3MS) at baseline and at follow-up. Cognitive decline was defined as a decline of >5 points. Results: In age-adjusted analyses, participants in the highest tertile of IL-6 or CRP performed nearly 2 points lower (worse) on baseline and follow-up 3MS (p < 0.001 for all) and declined by almost 1 point over the >2 years (p = 0.01 for IL-6 and p = 0.04 for CRP) compared with those in the lowest tertile. After multivariate adjustment, 3MS scores among participants in the highest tertile of IL-6 and CRP were similar at baseline but remained significantly lower at follow-up (p ≤ 0.05 for both). Those in the highest inflammatory marker tertile were also more likely to have cognitive decline compared with the lowest tertile for IL-6 (26 vs 20%; age-adjusted odds ratio [OR] = 1.34; 95% CI 1.06 to 1.69) and for CRP (24 vs 19%; OR = 1.41; 95% CI 1.10 to 1.79) but not for TNFα (23 vs 21%; OR = 1.12; 95% CI 0.88 to 1.43). There was no significant interaction between race and inflammatory marker or between nonsteroidal anti-inflammatory drug use and inflammatory marker on cognition. Conclusions: Serum markers of inflammation, especially IL-6 and CRP, are prospectively associated with cognitive decline in well-functioning elders. These findings support the hypothesis that inflammation contributes to cognitive decline in the elderly.

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.

The future of hip fractures in the United States. Numbers, costs, and potential effects of postmenopausal estrogen

Because of the increasing number of elderly people in the United States, the total number of hip fractures in persons 50 years and older will rise from 238,000 to 512,000 by the year 2040, with a concomitant increase in avoidable deaths, disability, and medical costs. The total annual cost of hip fractures (in 1984 dollars) will increase from approximately 7.2 billion dollars currently to 16 billion dollars in the year 2040. Universal use of estrogen therapy by postmenopausal white women may slow but not prevent this rise in hip fractures. New, effective, and widely applicable strategies to prevent hip fractures are urgently needed.

Physical activity, exercise, and inflammatory markers in older adults: Findings from the health, aging and body composition study

Objectives: To examine the association between physical activity and inflammatory markers, with consideration for body fatness and antioxidant use.

Limited literacy and mortality in the elderly: the health, aging, and body composition study.

BACKGROUND: While limited literacy is common and its prevalence increases with age, no prospective study has assessed whether limited literacy is associated with mortality in older adults.OBJECTIVE: To assess the association of limited literacy with mortality.DESIGN AND SETTING: Five-year prospective study from 1999 to 2004 of community-dwelling elders from Memphis, TN, and Pittsburgh, PA, who were from the Health, Aging, and Body Composition study. Subjects’ literacy was assessed with the Rapid Estimate of Adult Literacy in Medicine. Scores were categorzied into limited (0 to 8th grade reading level) or adequate literacy (≥9th grade reading level).PARTICIPANTS: Two thousand five hundred and twelve black and white elders without baseline functional difficulties or dementia.MEASUREMENTS: Time to death.RESULTS: Participants’ mean age was 75.6 years, 48% were male, 38% were black, and 24% had limited literacy; the median follow-up time was 4.2 years. Compared with those with adequate literacy, those with limited literacy had a higher risk of death (19.7% vs 10.6%) with a hazard ratio (HR) of 2.03 (95% confidence intervals [CI], 1.62 to 2.55). After adjusting for demographics and socioeconomic status, co-morbid conditions, self-rated health status, health-related behaviors, health care access measures, and psychosocial status, limited literacy remained independently associated with mortality (HR 1.75; 95% CI, 1.27 to 2.41).CONCLUSIONS: Limited literacy is independently associated with a nearly 2-fold increase in mortality in the elderly. Given the growth of the aging population and the prevalence of chronic diseases, the mechanisms by which limited literacy is associated with mortality in the elderly warrant further investigation.

Higher Inflammatory Marker Levels in Older Persons: Associations With 5-Year Change in Muscle Mass and Muscle Strength

BACKGROUND There is growing evidence that higher levels of inflammatory markers are associated with physical decline in older persons, possibly through the catabolic effects of inflammatory markers on muscle. The aim of this study was to investigate the association between serum levels of inflammatory markers and loss of muscle mass and strength in older persons. METHODS Using data on 2,177 men and women in the Health, Aging, and Body Composition Study, we examined 5-year change in thigh muscle area estimated by computed tomography and grip and knee extensor strength in relation to serum levels of interleukin-6 (IL-6), C-reactive protein, tumor necrosis factor-alpha (TNF-alpha), and soluble receptors (measured in a subsample) at baseline. RESULTS Higher levels of inflammatory markers were generally associated with greater 5-year decline in thigh muscle area. Most associations, with the exception of soluble receptors, were attenuated by adjustment for 5-year change in weight. Higher TNF-alpha and interleukin-6 soluble receptor levels remained associated with greater decline in grip strength in men. Analyses in a subgroup of weight-stable persons showed that higher levels of TNF-alpha and its soluble receptors were associated with 5-year decline in thigh muscle area and that higher levels of TNF-alpha were associated with decline in grip strength. CONCLUSIONS TNF-alpha and its soluble receptors showed the most consistent associations with decline in muscle mass and strength. The results suggest a weight-associated pathway for inflammation in sarcopenia.