Hyperhomocysteinaemia in young adults is not associated with impaired endothelial function

A mild to moderate elevation of the total homocysteine concentration (tHcy) is now recognized as a risk factor for vascular disease. It is also associ ated with endothelial dysfunction in middle-aged and elderly individuals wi thout overt atherosclerotic vascular disease. This is important, as endothe lial dysfunction is a well recognized early and potentially reversible mark er of the atherosclerotic process. We investigated whether mild hyperhomocy steinaemia was associated with endothelial dysfunction in otherwise healthy young males. We compared endothelial function, by measuring forearm blood flow, in 17 males with mild hyperhomocysteinaemia (defined as tHcy > 10 mu mol/l) and 14 controls with low tHcy (defined as < 5 <mu>mol/l). Forearm bl ood flow was measured in response to the intra-arterial infusion of acetylc holine (endothelial-dependent response) or sodium nitroprusside (endothelia l-independent response). Responses to the vasoactive substances were expres sed as the area under the cu rye of the change in forearm blood flow from b aseline. Data are given as mean (95% confidence interval). The two groups w ere well matched for age, body mass index, pulse rate and blood pressure, t Hcy was significantly different between the groups [12.3 (10.4-14.2) mu mol /l compared with 4.9 (4.6-5.1) mu mol/l; P < 0.001]. Concentrations of vita min B-12 and folate were significantly higher in the control group. There w as no difference in basal forearm blood flow between the group with mild hy perhomocysteinaemia and the controls, and both the endothelial-dependent [3 7.5 (26.2-38.8) and 35.3 (26.1-44.4) arbitrary units respectively] and -ind ependent [26.1 (22.2-29.9) and 25.9 (21.0-30.8) units respectively] respons es were not significantly different between the groups. Thus the present st udy demonstrates that, in healthy adults, mild elevation of tHcy was not as sociated with impaired endothelial-dependent vasodilation. These data sugge st an age effect with regard to homocysteine and endothelial dysfunction. T he development of vascular disease in individuals with hyperhomocysteinaemi a may only result with higher concentrations or after prolonged exposure.