Homocysteine and heart failure: a review of investigations from the Framingham Heart Study.

High plasma homocysteine levels are associated with a moderately increased risk of cardiovascular disease, particularly of atherosclerotic events. We review the association of plasma homocysteine with heart failure, with a specific focus on a series of previously published investigations from the community-based Framingham Heart Study that evaluated the relations of plasma homocysteine levels with overt heart failure, and with its key antecedents, echocardiographic left ventricular (LV) mass and hypertension. In the Framingham sample, higher plasma homocysteine levels were associated with increased risk of new-onset heart failure in both men and women, with a more continuous and graded relation being observed in women. A positive relation between homocysteine and LV mass was observed in women, but not in men; this may underlie the stronger relations of homocysteine to heart failure risk in women. Plasma homocysteine was not associated with hypertension incidence prospectively in either sex. The relations of increased homocysteine to heart failure (in both sexes) and to greater LV mass (in women) noted in the Framingham sample should be confirmed in other community-based samples. Secondary analyses of heart failure outcomes in ongoing randomized clinical trials may provide insights into whether lowering of plasma homocysteine levels is associated with a reduction in LV mass and/or a reduction of heart failure risk.