Homocysteinemia: new information about an old risk factor for vascular disease.

OBJECTIVE To determine the importance of homocysteinemia as a risk factor for atherosclerotic vascular disease. DESIGN Literature review of published studies homocysteine as risk factor for atherosclerotic vascular disease. METHODS MEDLINE search from 1969 to 1998 using homocysteine and vascular disease as search terms, from which 13 articles were selected for review. RESULTS Homocysteine is a sulfur containing amino acid derivative formed during methionine metabolism. Inherited deficiencies of cystathionine B synthase or MTHF reductase result in markedly elevated plasma homocysteine levels and homocystinuria. Although rare, hereditary homocystinuria results in a variety of life threatening vascular complications occurring at a young age. Lesser degrees of homocysteinemia may result from vitamin B12, folate and pyridoxine deficiencies as well as a recently described mutation of the MTHF reductase gene. Homocysteinemia from these causes has been shown to increase the risk of coronary artery disease, peripheral artery disease, stroke, and venous thrombosis. Postulated mechanisms for this association are discussed. CONCLUSION Homocysteinemia is a risk factor for premature vascular disease. The strength of this association is similar to that due to hyperlipidemia and tobacco use. Although vitamin supplementation with folic acid, B12, and B6 is able to reduce homocysteine levels in many persons, proof of the effectiveness of vitamin treatment in preventing or halting the progression of vascular disease is not yet available.