Plasma Leptin Levels and Incidence of Heart Failure, Cardiovascular Disease, and Total Mortality in Elderly Individuals
- Wolfgang Lieb, MD1,
- Lisa M. Sullivan, PHD2,
- Tamara B. Harris, MD3,
- Ronenn Roubenoff, MD, MHS4,
- Emelia J. Benjamin, MD, SCM1,2,5,
- Daniel Levy, MD1,6,
- Caroline S. Fox, MD, MPH1,6,7,
- Thomas J. Wang, MD, MPH1,8,
- Peter W. Wilson, MD9,
- William B. Kannel, MD, MPH1 and
- Ramachandran S. Vasan, MD1,5
- 1Framingham Heart Study, Framingham, Massachusetts;
- 2Department of Biostatistics and Epidemiology, Boston University School of Public Health, Boston, Massachusetts;
- 3Intramural Research Program, Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, Maryland;
- 4Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts;
- 5Whitaker Cardiovascular Institute, Preventive Medicine and Cardiology Sections, Boston University School of Medicine, Boston, Massachusetts;
- 6The Center for Population Studies of the National Heart, Lung, and Blood Institute, Bethesda, Maryland;
- 7Endocrinology Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts;
- 8Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts;
- 9Emory University School of Medicine, Atlanta, Georgia.
- Corresponding author: Ramachandran S. Vasan, vasan{at}bu.edu.
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.
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Received August 29, 2008.
- Accepted December 22, 2008.
- © 2009 by the American Diabetes Association.
