Does Homocysteine Promote Atherosclerosis?

The hypothesis that homocysteine is atherogenic was proposed more than 30 years ago by Kilmer McCully,1 who observed vascular lesions in children with inherited disorders of methionine metabolism. Since McCully’s pioneering observations in 1969, a large number of epidemiological studies have confirmed that an elevation of total plasma homocysteine (tHcy) is prevalent in patients with stroke, myocardial infarction, peripheral vascular disease, and venous thrombosis.2 A significant association between hyperhomocysteinemia and clinical cardiovascular events has been observed in several large prospective studies, although a few prospective studies have failed to demonstrate this association.2 Nevertheless, hyperhomocysteinemia is now considered by many an independent risk factor for atherosclerotic vascular disease.3See p 1470 Homocysteine is a thiol amino acid, but only a small fraction ( 15 μmol/L and may be caused by genetic defects, renal insufficiency, certain drugs, or nutritional deficiencies of folate, vitamin B6, or vitamin B12.5 Even a mild elevation of plasma tHcy to levels within the high-to-normal range (10 to 15 μmol/L) may increase cardiovascular risk.2 Because plasma tHcy can often be lowered by oral administration of folic acid or combinations of B vitamins, there is growing enthusiasm for treatment of hyperhomocysteinemia as a strategy for prevention of cardiovascular disease and …