Plasma homocysteine and severity of atherosclerosis in young patients with lower-limb atherosclerotic disease

Elevated plasma homocysteine levels are recognized as an independent risk factor for atherosclerotic disease. It is not known (1) whether the severity of atherosclerotic disease is related to hyperhomocyst(e)inemia or (2) whether any such relation differs between fasting and post-methionine loading plasma homocysteine levels. Therefore, in 171 consecutive patients under 55 years of age with first symptoms of lower-limb disease, we examined the relation between severity of atherosclerosis and plasma homocysteine concentration. Severity of atherosclerotic disease was estimated from the prevalence of coronary artery disease and cerebrovascular disease and from the angiographic extent of lower-limb disease. Plasma homocysteine was measured after a period of fasting and in response to methionine loading (0.1 g/kg). In multivariate analysis, the prevalence of coronary artery disease plus cerebrovascular disease was related to both fasting and post-methionine homocysteine levels (odds ratio [OR] for the upper quartile versus the lower three quartiles, 2.8, 95% confidence interval [CI], 1.1 to 7.5; and OR 3.0: 95% CI, 1.1 to 7.8, respectively). The extent of lower-limb disease was weakly related to the fasting homocysteine level (partial correlation coefficient, .12; P=.17) and more strongly related to the postmethionine homocysteine level (partial correlation coefficient, .25; P=.003). These relations tended to be more pronounced in women than in men. They were independent of age, total serum cholesterol, blood pressure, and smoking habit. We concluded that the severity of atherosclerotic disease in young patients with lower-limb atherosclerotic disease is associated with high postmethionine and fasting homocysteine concentrations.