Does inflammation or undernutrition explain the low cholesterol-mortality association in high-functioning older persons? MacArthur studies of successful aging

OBJECTIVES: To explore the effect of inflammation and undernutrition on the association between hypocholesterolemia and higher overall mortality in high-functioning older persons. DESIGN: Prospective cohort study. SETTING: Three U.S. communities. PARTICIPANTS: A cohort of 870 participants from the MacArthur Studies of Successful Aging. MEASUREMENTS: Baseline information was obtained for serum levels of cholesterol, C-reactive protein, interleukin-6, and albumin; body mass index; prevalent medical conditions; health behaviors; and medications. Crude and multivariate logistic regression analyses were used to examine the association between serum total cholesterol levels and 7-year all-cause mortality, while adjusting for potential confounders. RESULTS: In univariate analysis, the risk ratio of low serum total cholesterol level (<169 mg/dL) for 7-year total mortality was 1.90 (95% confidence interval (CI) = 1.18-3.07). The multiple adjusted risk ratios were 1.82 (95% Cl = 1.10-3.00) after controlling for markers of inflammation and nutrition and 1.39 (95% Cl = 0.80-2.40) after adjustment for additional cardiovascular risk factors. Sex was an important confounding variable that contributed to the observed inverse association between low serum cholesterol and overall mortality in univariate analysis. CONCLUSIONS: Hypocholesterolemia is not an independent risk factor for increased overall mortality in high-functioning community-dwelling older men and women. The association between low total cholesterol and high mortality observed in crude analysis is mainly confounded by common cardiovascular risk factors, rather than underlying inflammation or undernutrition.