Plasma Leptin Levels and Incidence of Heart Failure, Cardiovascular Disease, and Total Mortality in Elderly Individuals

• Type of Material: Article
• Authors: Wolfgang Lieb, Framingham Heart Study; Lisa M. Sullivan, Boston University; Tamara B. Harris, National Institute on Aging; Ronenn Roubenoff, Tufts University; Emelia J. Benjamin, Framingham Heart Study; Daniel Levy, Framingham Heart Study; Caroline S. Fox, Framingham Heart Study; Thomas J. Wang, Framingham Heart Study; Peter Wilson, Emory University; William B. Kannel, Framingham Heart Study; Ramachandran S. Vasan, Framingham Heart Study
• Language: English
• Date: 2009-04-01
• Publisher: AMER DIABETES ASSOC
• Publication Version: Final Published Version
• Copyright Statement: © 2009 by the American Diabetes Association.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.2337/dc08-1596
• Title of Journal or Parent Work: DIABETES CARE
• Volume: 32
• Issue: 4
• Start Page: 612
• End Page: 616
• Grant/Funding Information: This work was supported through National Institutes of Health/National Heart, Lung, and Blood Institute Contracts N01-HC25195, N01-HV28178, K24-HL04334, and R01-DK080739. Contract N01-HC25195 funded the performance of examinations at which leptin levels were obtained. The other grants supported the interpretation of data and preparation of the manuscript.
• Keywords: OBESITY; Life Sciences & Biomedicine; MICE; RISK-FACTOR; WEIGHT; RAT VENTRICULAR MYOCYTES; Science & Technology; HYPERTROPHY; INSULIN; Endocrinology & Metabolism; MEN
• Research Categories: Health Sciences, Nutrition; Health Sciences, Public Health

Abstract

OBJECTIVE - Obesity predisposes individuals to congestive heart failure (CHF) and cardiovascular disease (CVD). Leptin regulates energy homeostasis, is elevated in obesity, and influences ventricular and vascular remodeling. We tested the hypothesis that leptin levels are associated with greater risk of CHF, CVD, and mortality in elderly individuals. RESEARCH DESIGN AND METHODS - We evaluated 818 elderly (mean age 79 years, 62% women) Framingham Study participants attending a routine examination at which plasma leptin was assayed. RESULTS - Leptin levels were higher in women and strongly correlated with BMI (P < 0.0001). On follow-up (mean 8.0 years), 129 (of 775 free of CHF) participants developed CHF, 187 (of 532 free of CVD) experienced a first CVD event, and 391 individuals died. In multivariable Cox regression models adjusting for established risk factors, log-leptin was positively associated with incidence of CHF and CVD (hazard ratio [HR] per SD increment 1.26 [95% CI 1.03-1.55] and 1.28 [1.09-1.50], respectively). Additional adjustment for BMI nullified the association with CHF (0.97 [0.75-1.24]) but only modestly attenuated the relation to CVD incidence (1.23 [1.00-1.51], P = 0.052). We observed a nonlinear, U-shaped relation between log-leptin and mortality (P = 0.005 for quadratic term) with greater risk of death evident at both low and high leptin levels. CONCLUSIONS - In our moderate-sized community-based elderly sample, higher circulating leptin levels were associated with a greater risk of CHF and CVD, but leptin did not provide incremental prognostic information beyond BMI. Additional investigations are warranted to elucidate the U-shaped relation of leptin to mortality.