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 cholesterol levels in the high normal range are associated with impaired endothelium-dependent vasodilation. Methods and Results We studied leg blood flow (LBF) responses to graded intrafemoral artery infusions of the endothelium-dependent vasodilator methacholine chloride (MCh) or the endothelium-independent vasodilator sodium nitroprusside (SNP) in normal volunteers exhibiting a wide range of total cholesterol levels 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 normal group was decreased by nearly 50% compared with the low normal group (146 +/- 13% versus 268 +/- 34%, P < .01). There was a negative correlation between total cholesterol levels and maximal endothelium-dependent vasodilation (total cholestero,l r = -.41, P < .02; LDL cholesterol, r = -.42, P < .02). On the other hand, LBF responses to the endothelium-independent vasodilator SNP did not differ between groups. Conclusions These data suggest that an inverse and continuous relationship exists between the prevailing cholesterol level and endothelium-dependent vasodilation. Moreover, cholesterol levels even in the normal range may be associated with endothelial dysfunction, thus potentially contributing to the increased risk of macrovascular disease conferred by cholesterol elevations.