Brenda W. J. H. Penninx

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.

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.

Exploring the effect of depression on physical disability: longitudinal evidence from the established populations for epidemiologic studies of the elderly.

OBJECTIVESnThis study examined the effect of depression on the incidence of physical disability and the role of confounding and explanatory variables in this relationship.nnnMETHODSnA cohort of 6247 subjects 65 years and older who were initially free of disability was followed up for 6 years. Baseline depression was assessed by the Center for Epidemiological Studies Depression Scale. Disability in mobility and disability in activities of daily living were measured annually.nnnRESULTSnCompared with the 5751 nondepressed subjects, the 496 depressed subjects had a relative risk (95% confidence interval) of 1.67 (1.44, 1.95) and 1.73 (1.54, 1.94) for incident disability in activities of daily living and mobility, respectively. Adjustment for sociodemographic characteristics and baseline chronic conditions reduced the risks to 1.39 (1.18, 1.63) and 1.45 (1.29, 1.93), respectively. Less physical activity and fewer social contacts among depressed persons further explained part of their increased disability risk.nnnCONCLUSIONSnDepression in older persons may increase the risk for incident disability. This excess risk is partly explained by depressed persons decreased physical activity and social interaction. The role of other factors (e.g., biological mechanisms) should be examined.

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.

Change in muscle strength explains accelerated decline of physical function in older women with high interleukin-6 serum levels

OBJECTIVES: To test whether accelerated sarcopenia in older persons with high interleukin (IL)‐6 serum levels plays a role in the prospective association between inflammation and disability found in many studies.

Anemia is associated with disability and decreased physical performance and muscle strength in the elderly

Objectives: To examine the association between anemia and disability, physical performance, and muscle strength in older persons.

Inflammatory markers and cardiovascular disease (The Health, Aging and Body Composition [Health ABC] Study) ☆

This study investigates the association of several inflammatory markers with subclinical and clinical cardiovascular disease in older men and women. Data are from the baseline assessment of 3,045 well-functioning persons aged 70 to 79 years, participating in the Health, Aging and Body Composition study. The study sample was divided into 3 groups: cardiovascular disease (diagnosis of congestive heart failure, coronary artery disease, peripheral artery disease, or stroke), subclinical cardiovascular disease (positive findings on the Rose questionnaire for angina or claudication, ankle-brachial index <0.9, or electrocardiographic abnormalities), and no cardiovascular disease. Serum levels of interleukin (IL)-6, C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha, and the soluble receptors IL-6 soluble receptor, IL-2 soluble receptor, TNF soluble receptor I, and TNF soluble receptor II were assessed. Of those with IL-6 levels in the highest compared with the lowest tertile, the odds ratio (OR) for subclinical cardiovascular disease was 1.58 (95% confidence interval [CI] 1.26 to 1.97) and for clinical cardiovascular disease was 2.35 (95% CI 1.79 to 3.09). A similar association was found for TNF-alpha (OR 1.48, 95% CI 1.16 to 1.88 and OR 2.05, 95% CI 1.55 to 2.72, respectively). In adjusted analyses, CRP was not significantly associated with overall subclinical or clinical cardiovascular disease, although additional analyses did find a strong specific association between CRP and congestive heart failure (OR 1.64, 95% CI 1.11 to 2.41). Of the soluble cytokine receptors, only TNF soluble receptor I showed a significant association with clinical cardiovascular disease. Thus, our findings suggest an important role for IL-6 and TNF-alpha in clinical as well as subclinical cardiovascular disease. In this study, CRP had a weaker association with cardiovascular disease than the cytokines.

Added Value of Physical Performance Measures in Predicting Adverse Health‐Related Events: Results from the Health, Aging and Body Composition Study

OBJECTIVES: To determine how three different physical performance measures (PPMs) combine for added utility in predicting adverse health events in elders.

Anemia and decline in physical performance among older persons

PURPOSEnAnemia is prevalent in old age and is potentially modifiable, but its effects on physical function have not been determined. We examined whether anemia in older persons increases the risk of subsequent decline in physical function, as measured by objective performance-based tests.nnnMETHODSnParticipants in this 4-year prospective cohort study included 1146 participants, aged 71 years or older, living in Iowa and Washington counties, Iowa. Anemia was defined according to World Health Organization (WHO) criteria as a hemoglobin concentration below 12 g/dL in women and below 13 g/dL in men. An assessment of standing balance, a timed 2.4-m walk, and a timed test of five chair rises were used to assess physical performance; these were combined into a 0 (poor) to 12 (excellent) summary scale.nnnRESULTSnAfter adjustment for baseline performance score, health status, and demographic characteristics, anemia was associated with greater mean decline in physical performance over 4 years; the adjusted mean decline was 2.3 (95% confidence interval [CI]: 1.7 to 2.8) in subjects with anemia and 1.4 (95% CI: 1.2 to 1.5) in those without anemia (P = 0.003). The association between anemia and greater physical decline was also present in participants who were free of diseases associated with anemia (cancer, infectious disease, and renal failure), and after adjustment for serum cholesterol, iron, and albumin levels. Persons with borderline anemia, a hemoglobin concentration within 1 g/dL above the WHO criteria, also showed greater mean physical decline (1.8; 95% CI: 1.5 to 2.2) than did those with higher hemoglobin concentrations (P = 0.02).nnnCONCLUSIONnThis study suggests that anemia in old age is an independent risk factor for decline in physical performance.

Effects of Social Support and Personal Coping Resources on Depressive Symptoms: Different for Various Chronic Diseases?

Effects of psychosocial coping resources on depressive symptoms were examined and compared in older persons with no chronic disease or with recently symptomatic diabetes mellitus, lung disease, cardiac disease, arthritis, or cancer. The 719 persons without diseases reported less depressive symptoms than the chronically ill. Direct favorable effects on depressive symptoms were found for having a partner, having many close relationships, greater feelings of mastery, greater self-efficacy expectations, and high self-esteem. Buffer effects were observed for feelings of mastery, having many diffuse relationships, and receiving emotional support. Buffer effects were differential across diseases for emotional support (in cardiac disease and arthritis only) and for diffuse relationships (in lung disease). Receiving instrumental support was associated with more depressive symptoms, especially in diabetes patients.