Homocysteine and Cardiovascular Disease

Abstract

See related article, pages 598–606 An elevated plasma level of homocysteine has long been known as an independent predictor of cardiovascular disease.1,2 However, in the absence of a clear mechanism linking homocysteine to cardiovascular disease, there has been an ongoing debate about whether this relationship is one of cause and effect or whether an elevated level of plasma homocysteine is an epiphenomenon, reflecting the presence of some other proatherogenic factor that is actually responsible for the cardiovascular disease. In the current issue of this journal, Liao et al3 suggest that the mechanistic link may be a homocysteine-induced reduction in the concentration of high density lipoproteins (HDLs). Liao et al3 report that homocysteine reduces the concentration of HDL cholesterol in plasma by inhibiting the hepatic synthesis of apoA-I, the main HDL apolipoprotein. This conclusion supports the findings from another recent study by Mikael et al4 who also reported that homocysteine inhibits apoA-I synthesis. The results of these 2 studies not only explain the documented inverse correlation between the plasma concentrations of HDL cholesterol and homocysteine5,6 but also raise the real possibility that a homocysteine-induced inhibition of apoA-I synthesis is the mechanism linking homocysteine to the development of atherosclerosis. A low concentration of HDL cholesterol has been shown in numerous human population studies to be highly predictive of premature cardiovascular disease.7,8 Furthermore, treatments that increase the level of HDL cholesterol in plasma in both animals9,10 and humans11,12 reduce the progression or even promote …