On the basis of recent retrospective and prospective studies, it is now widely accepted that increased total plasma homocysteine is a risk factor for cardiovascular disease. Impaired enzyme function as a result of genetic mutation or deficiency of the essential B vitamins folic acid, B12, and B6 can lead to hyperhomocysteinemia. Oxidized forms of homocysteine account for 98-99% of total plasma homocysteine. Although there is uncertainty as to whether increased homocysteine is causal or merely a proxy for cardiovascular disease, several lines of evidence suggest that it may play a role in atherothrombotic disease. Homocysteine appears to alter the anticoagulant properties of endothelial cells to a procoagulant phenotype. Mildly increased homocysteine causes dysfunction of the vascular endothelium. Folic acid effectively lowers homocysteine concentration in the plasma. Intervention studies are urgently needed to determine if lowering homocysteine is effective in decreasing the morbidity and mortality of cardiovascular disease.
