Homocysteine and arterial occlusive disease: a concise review.

Abstract

Many cross-sectional and prospective studies have shown that raised serum/plasma levels of total homocysteine increase the risk of coronary, cerebral, and peripheral artery disease. The risk associated with hyperhomocysteinemia appears to be concentration-dependent and not attributable to traditional risk factors. The odds ratio for ischemic heart disease has been estimated to be 1.4 for every 5 mumol/l increase of total plasma homocysteine. Median fasting total plasma homocysteine in adult males is approximately 10 mumol/l. Mild hyperhomocysteinemia is estimated to occur in 5-10% of the general population. Plasma concentrations are increased as a result of age, male gender, impaired renal function, low vitamin B intake, and genetically-determined defects of the enzymes involved in homocysteine metabolism. Folate supplements can reduce total homocysteine levels by approximately 25%. Studies in vitro and in vivo indicate that homocysteine can impair endothelial function. Despite increasing recognition of hyperhomocysteinemia as a risk factor for arterial occlusive disease, irrefutable proof that mild hyperhomocysteinemia contributes directly to the pathogenesis of atherothrombosis will come if interventions to lower total homocysteine reduce cardiovascular events. Family studies may also provide evidence of causality if genetic causes of hyperhomocysteinemia are found to segregate with disease.