ENDOTHELIAL DYSFUNCTION IS ASSOCIATED WITH CHOLESTEROL LEVELS IN THE HIGH NORMAL RANGE IN HUMANS

Background The purpose of this study was to test the hypothesis that c holesterol levels in the high normal range are associated with impaire d endothelium-dependent vasodilation. Methods and Results We studied l eg blood flow (LBF) responses to graded intrafemoral artery infusions of the endothelium-dependent vasodilator methacholine chloride (MCh) o r the endothelium-independent vasodilator sodium nitroprusside (SNP) i n normal volunteers exhibiting a wide range of total cholesterol level s within the normal range (< 75th percentile). LBF increased in a dose -dependent fashion in response to the femoral artery infusions of MCh and SNP (P < .001). LBF responses to MCh were significantly blunted (P < .001) in subjects with high normal cholesterol (195 +/- 6 mg/dL, n = 13) compared with subjects with low normal cholesterol (146 +/- 5 mg /dL, n = 20). Maximal endothelium-dependent vasodilation in the high n ormal group was decreased by nearly 50% compared with the low normal g roup (146 +/- 13% versus 268 +/- 34%, P < .01). There was a negative c orrelation between total cholesterol levels and maximal endothelium-de pendent vasodilation (total cholestero,l r = -.41, P < .02; LDL choles terol, r = -.42, P < .02). On the other hand, LBF responses to the end othelium-independent vasodilator SNP did not differ between groups. Co nclusions These data suggest that an inverse and continuous relationsh ip exists between the prevailing cholesterol level and endothelium-dep endent vasodilation. Moreover, cholesterol levels even in the normal r ange may be associated with endothelial dysfunction, thus potentially contributing to the increased risk of macrovascular disease conferred by cholesterol elevations.