Hyperhomocystcinemia as a cardiovascular risk factor. Current concepts

Resume Hyperhomocysteinemia is hypothesized to be a cardiovascular risk factor. Severe hyperhomocysteinemia due to rare genetic impairments of homocysteine metabolism predisposes to atherothrombosis. Even partial correction of homocysteine levels in patients with severe hyperhomocysteinemia leads to significant reduction in cardiovascular risk. Moderate hyperhomocysteinemia is common in the general population and is associated with the increased risk of cardiovascular disease. Moderate hyperhomocysteinemia leads to endothelial dysfunction, increased susceptibility to thrombosis and accelerated progression of atherosclerosis in animal models. Extensive epidemiological and experimental evidence lead to the hypothesis that correction of moderate hyperhomocysteinemia may significantly lower cardiovascular risk. Paradoxically, several large clinical trials failed to demonstrate any benefit from lowering of homocysteine levels in moderate hyperhomocysteinemia. This article discusses the current understanding of hyperhomocysteinemia as a cardiovascular risk factor in light of the negative results of clinical trials of homocysteine lowering therapy in moderate hyperhomocysteinemia.