Endothelial Dysfunction Is Associated With Cholesterol Levels in the High Normal Range in Humans

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Abstract
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 (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.

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