Elevated plasma concentrations of total homocysteine (homocyst(e)ine) are associated with increased risk of coronary artery disease, cerebrovascular disease, peripheral vascular disease, and thrombosis. The relationship between plasma homocyst(e)ine concentrations and risk of atherosclerosis is independent and is graded even for values between the 50th and 95th percentiles. Hyperhomocyst(e)inemia has been detected in 10 to 40% of subjects with myocardial infarction, and it appears to be most prevalent among such individuals with normal or low plasma cholesterol levels. Although a cause and effect link between homocyst(e)ine and atherosclerosis has not been established, several lines of evidence suggest that homocysteine is atherogenic and not merely a marker for increased risk. Potential mechanisms by which homocyst(e)ine might contribute to atherogenesis include direct cytotoxic effects, generation of reactive oxygen species, diminished release of nitric oxide (a primary mediator of endothelium-dependent vasodilation), endothelial dysfunction, potentiation of LDL oxidation, stimulation of smooth muscle cell proliferation, and possible abnormalities in platelet function. Screening for hyperhomocyst(e)inemia is indicated in all individuals with atherosclerosis or a strong family history of arterial occlusive disease. Folic acid deficiency is a common cause of elevated plasm homocyst(e)ine concentrations, particularly among subjects with mutations in the gene for methylenetetrahydrofolate reductase. Deficiencies of vitamins B6 and B12 also can contribute to hyperhomocyst(e)inemia. Successful treatment of hyperhomocyst(e)inemia usually is accomplished by increasing intake of folic acid above 400 to 800 μg daily, with the addition of vitamins B6 and B12 if indicated. Although lowering of plasma homocyst(e)ine levels has not been proven to reduce risk of atherosclerosis, the treatment is relatively safe and inexpensive and is expected to provide benefit. Thus, there are not compelling reasons not to provide therapy. Within the next few years, the results of intervention trials are expected to become available that will help substantiate the anticipated effects of treatment on atherosclerotic risk.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism