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Ramachandran S. Vasan, MD; Alexa Beiser, PhD; Ralph B. D'Agostino, PhD; Daniel Levy, MD; Jacob Selhub, PhD; Paul F. Jacques, ScD; Irwin H. Rosenberg, MD; Peter W. F. Wilson, MD

JAMA. 2003;289:1251-1257.

Context  Elevated plasma homocysteine levels are associated with increased risk of vascular disease. It is unclear whether elevated homocysteine levels are a risk factor for congestive heart failure (CHF).

Objective  To study prospectively the association between nonfasting plasma homocysteine and incidence of CHF.

Design, Setting, and Participants  Community-based prospective cohort study of 2491 adults (mean age 72 years, 1547 women) who participated in the Framingham Heart Study during the 1979-1982 and 1986-1990 examinations and were free of CHF or prior myocardial infarction (recognized or unrecognized) at baseline.

Main Outcome Measure  Incidence of a first episode of CHF during an 8-year follow-up period.

Results  During follow-up, 156 subjects (88 women) developed CHF. In multivariable analyses controlling for established risk factors for CHF including the occurrence of myocardial infarction (recognized or unrecognized) during follow-up, plasma homocysteine levels higher than the sex-specific median value were associated with an adjusted hazards ratio for heart failure of 1.93 in women (95% confidence interval, 1.19-3.14) and 1.84 in men (95% confidence interval, 1.06-3.17). The relation of plasma homocysteine levels to CHF risk was more continuous in women than in men. In analyses restricted to participants without any manifestation of coronary heart disease at baseline, the association of plasma homocysteine levels with risk of CHF was maintained in men and women.

Conclusions  An increased plasma homocysteine level independently predicts risk of the development of CHF in adults without prior myocardial infarction. Additional investigations are warranted to confirm these findings.

Author Affiliations: National Heart, Lung, and Blood Institute's Framingham Heart Study (Drs Vasan, Beiser, D' Agostino, Levy, and Wilson), Framingham, Mass; Cardiology Section (Dr Vasan), Endocrinology Section (Dr Wilson), Preventive Medicine and Epidemiology (Drs Vasan, Levy, and Wilson), Department of Medicine, Boston University School of Medicine, and Department of Biostatistics, Boston University School of Public Health (Dr Beiser); and Department of Mathematics (Dr D'Agostino), Boston University, Boston, Mass; the Divisions of Cardiology and Clinical Epidemiology, Beth Israel Deaconess Medical Center (Dr Levy), Boston, Mass; and the National Heart, Lung, and Blood Institute, Bethesda, Md (Dr Levy); the Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging (Drs Selhub, Jacques, and Rosenberg) at Tufts University, Boston, Mass.

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