Endothelial dysfunction is associated with cholesterol levels in the high normal range in humans

• Published in: Circulation (New York, N.Y.) Vol. 96; no. 10; pp. 3287 - 3293
• Main Authors: STEINBERG, H. O, BAYAZEED, B, HOOK, G, JOHNSON, A, CRONIN, J, BARON, A. D
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 18.11.1997; American Heart Association, Inc
• Subjects: Adult; Biological and medical sciences; Blood Pressure - drug effects; Cardiovascular system; Cholesterol - blood; Endothelium, Vascular - physiopathology; Female; Femoral Artery; Hemodynamics - drug effects; Hemodynamics - physiology; Humans; Injections, Intra-Arterial; Investigative techniques, diagnostic techniques (general aspects); Leg - blood supply; Male; Medical sciences; Methacholine Chloride - pharmacology; Nitroprusside - pharmacology; Osmolar Concentration; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Reference Values; Regional Blood Flow - drug effects; Vascular Resistance - drug effects; Vasodilator Agents - pharmacology; Human; Pharmacologic test; Femoral artery; Methacholine chloride; Lipids; Exploration; Concentration; Respiratory system; Artery; Cholesterol; Blood plasma; Relation; Vasomotricity; Blood vessel
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.96.10.3287

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. 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 cholesterol, 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. 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.