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CLINICAL RESEARCH: HEART FAILURE

Resistin, Adiponectin, and Risk of Heart Failure

The Framingham Offspring Study

David S. Frankel, MD^_*, Ramachandran S. Vasan, MD^,, Ralph B. D'Agostino, Sr, PhD, Emelia J. Benjamin, MD, ScM^,,, Daniel Levy, MD^,||, Thomas J. Wang, MD^,¶ and James B. Meigs, MD, MPH^,#,_*

^_* Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
Framingham Heart Study, Framingham, Massachusetts
Department of Medicine, School of Medicine, Boston University, Boston, Massachusetts
Department of Epidemiology, School of Public Health, Boston University, Boston, Massachusetts
^|| National Heart, Lung, and Blood Institute, Bethesda, Maryland
^¶ Division of Cardiology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
^# General Medicine Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts

Manuscript received April 9, 2008; revised manuscript received June 11, 2008, accepted July 1, 2008.

^_* Reprint requests and correspondence: Dr. James B. Meigs, General Medicine Division, Massachusetts General Hospital, 50 Staniford Street, 9th Floor, Boston, Massachusetts 02114 (Email: jmeigs{at}partners.org).

Objectives: We tested the association of the adipokines resistin and adiponectin with incident heart failure.

Background: Abnormal concentrations of adipokines may partially explain the association between obesity and heart failure.

Methods: We related circulating adipokine concentrations to the incidence of heart failure in 2,739 participants in the Framingham Offspring Study.

Results: During 6 years of follow-up, 58 participants developed new-onset heart failure. In proportional hazards models (adjusting for age, sex, blood pressure, antihypertensive treatment, diabetes, smoking, total/high-density lipoprotein cholesterol ratio, prevalent coronary heart disease, valvular heart disease, left ventricular hypertrophy, and estimated glomerular filtration rate) using the lowest third of the resistin distribution as the referent, the hazard ratios for heart failure in the middle and top thirds were 2.89 (95% confidence interval [CI]: 1.05 to 7.92) and 4.01 (95% CI: 1.52 to 10.57), respectively (p = 0.004 for trend). Additional adjustment for body mass index, insulin resistance (measured with the homeostasis model), C-reactive protein, and B-type natriuretic peptide did not substantively weaken this association (multivariable hazard ratios [HRs]: 2.62 and 3.74, p = 0.007). In the maximally adjusted model, each SD increment in resistin (7.45 ng/ml) was associated with a 26% increase in heart failure risk (95% CI: 1% to 60%). Concentrations of adiponectin were not associated with heart failure (multivariable HRs: 0.87 and 0.97, p = 0.9).

Conclusions: Increased circulating concentrations of resistin were associated with incident heart failure, even after accounting for prevalent coronary heart disease, obesity, and measures of insulin resistance and inflammation. The findings suggest a role for resistin in human disease and a novel pathway to heart failure.

Key Words: heart failure • resistin • adiponectin • adipokines • epidemiology

Abbreviations and Acronyms   BMI = body mass index   CHD = coronary heart disease   CI = confidence interval   HDL = high-density lipoprotein   HOMA-IR = insulin resistance measured with the homeostasis model   HR = hazard ratio   UACR = urine albumin/creatinine ratio

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