HYPERHOMOCYST(E)INEMIA IS A RISK FACTOR FOR ARTERIAL ENDOTHELIAL DYSFUNCTION IN HUMANS

Background Hyperhomocyst(e)inemia is associated with premature periphe ral vascular, cerebrovascular, and coronary artery disease. Because ho mocysteine has been found to be damaging to endothelial cells in anima l and cell culture studies, we evaluated the association between hyper homocysteinemia and arterial endothelial dysfunction (a marker of earl y atherosclerosis) in asymptomatic adult subjects. Methods and Results Using high-resolution ultrasound, we measured endothelium-dependent f low-mediated dilation (EDD) and endothelium-independent nitroglycerin- induced dilation (GTN) of the brachial artery in 14 prospectively defi ned hyperhomocysteinemic (mean plasma homocysteine, 34.8+/-8.5 mu mol/ L), nonsmoking, healthy subjects aged 53+/-9 years and 14 control subj ects with low plasma homocysteine levels (9.9+/-3.2 mu mol/L). The two groups were well matched for age; sex; body mass index; blood pressur e, blood cholesterol, folate, and vitamin B-12 levels; and vessel diam eter. EDD was significantly lower in hyperhomocysteinemic subjects (6. 5+/-1.7%) than in subjects with low homocysteine levels (10.8+/-1.7%) (P<.001). GTN responses were similar in the two subject groups (P=.90) . Multivariate analysis confirmed homocysteine level as the strongest predictor for impaired EDD, independent of age, sex, body mass index, or blood pressure, folate, vitamin B-12, and cholesterol levels. Concl usions Hyperhomocysteinemia is an independent risk factor for arterial endothelial dysfunction in healthy middle-aged adults.