Homocysteine as a novel risk factor for atherosclerosis

Abstract

Homocysteine is a sulfhydryl amino acid formed during metabolism of methionine. Increasing evidence suggests that homocyst(e)ine may act as an independent risk factor for ischemic heart disease, cerebrovascular disease, and peripheral arterial disease. Recent prospective data have shown that homocyst(e)ine levels in the top 20% of the population increase the risk for ischemic heart disease by approximately twofold. Homocyst(e)ine seems to promote the progression of atherosclerosis by causing endothelial dysfunction, increasing oxidant stress, and promoting vascular smooth muscle growth. Recent human studies using methionine loading to experimentally induce moderate hyperhomocyst(e)inemia have demonstrated rapid and profound impairment of resistance and conduit artery endothelial function. No data are available from randomized, controlled trials of the effects of lowering plasma homocyst(e)ine on atherosclerotic vascular events; however, screening for hyperhomocyst(e)inemia should be actively considered in individuals with progressive and unexplained atherosclerosis. Both fasting and postmethionine load homocyst(e)ine levels should be measured. B vitamins, including folic acid and vitamins B6 and B12 are the mainstay of treatment of patients with hyperhomocyst(e)inemia. Primary prevention strategies await the completion of long-term, randomized, prospective studies.