Hyperhomocysteinemia and atherosclerotic vascular disease - Pathophysiology, screening, and treatment

Hyperhomocysteinemia has recently been identified as an important risk factor for atherosclerotic vascular disease. This article reviews homocysteine metabolism, causes of hyperhomocysteinemia, the pathophysiological findings of this disorder, and epidemiological studies of homocysteine and vascular disease. Screening for hyperhomocysteinemia should be considered for patients at high risk for vascular disease or abnormalities of homocysteine metabolism. For primary prevention of vascular disease, treatment of patients with homocysteine levels of 14 mu mol/L or higher should be considered. For secondary prevention, treatment of patients with homocysteine levels of 11 mu mol/L or higher should be considered. Treatment is most conveniently administered as a folic acid supplement (400-1000 pg) and a high-potency multivitamin that contains at least 400 mu g of folate. Higher doses of folic acid and cyanocobalamin supplements may be required in some patients. Until prospective clinical trial data become available, these conservative recommendations provide a safe, effective, and evidence-based approach to the diagnosis, evaluation, and management of patients with hyperhomocysteinemia.