Homocysteine: evidence for a causal relationship with cardiovascular disease.

Elevated plasma homocysteine levels are associated with vascular disease and thrombosis. Premature atherosclerosis and thromboembolism are seen in children who are homozygotes for defects in enzymes responsible for the metabolism of homocysteine. Adults with heterozygous defects have less marked elevations of homocysteine, and onset of atherosclerosis and vascular disease are delayed into the fourth and fifth decade of life. Homocysteine can damage vascular endothelium, cause proliferation of vascular smooth muscle, activate platelets, promote lipid peroxidation, and activate the coagulation cascade. Epidemiologic studies have linked elevations in plasma homocysteine with coronary artery disease, cerebrovascular disease, and thromboembolism. Folic acid, in combination with vitamins B6 and B12, can normalize homocysteine levels in most patients. Although randomized trials assessing the efficacy of homocysteine reduction have yet to be completed, treatment with vitamin supplementation should be considered in all patients at risk for vascular disease.