Homocysteine: a novel risk factor in vascular disease

Abstract

Homocysteine is a sulphydryl-containing aminoacid derived from the metabolic demethylation of methionine. Moderately raised concentrations of total homocysteine (tHcy) have been correlated with an increased risk of atherothrombotic vascular events. The prevalence of hyperhomocysteinaemia has been estimated to be about 5% in the general population, and 13–47% among patients with symptomatic atherosclerotic vascular disease. Nutritional deficiencies in the vitamin cofactors (folate, vitamin B12, and vitamin B6) required for homocysteine metabolism may promote hyperhomocysteinaemia. Clinical and experimental studies suggest that high homocysteine concentrations may cause the atherogenic and thrombotic tendencies of homocystinuric and hyperhomocysteinaemic patients. Experimental evidence suggests that the atherogenic propensity associated with hyperhomocysteinaemia results from endothelial dysfunction and injury followed by platelet activation and thrombus formation. The treatment of hyperhomocysteinaemia varies with the underlying cause; however, vitamin supplementation (with folic acid, pyridoxine [vitamin B6], and vitamin B12) is generally effective in reducing homocysteine concentrations. Before advocating widespread screening of patients with atherosclerotic vascular disease, we must have a clearer understanding of the clinical efficacy of potential therapeutic interventions. Prospective, randomized clinical trials, however, will be necessary to determine the effect of vitamin supplementation on cardiovascular morbidity and mortality.