Rapid Effect of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibition on Coronary Endothelial Function

Abstract

Treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) decreases cardiovascular event rates in hypercholesterolemic patients. Whether statins exert effects within 24 hours on the coronary vasculature in patients with endothelial dysfunction has not been elucidated. Twenty-seven patients with stable angina pectoris and average low-density lipoprotein cholesterol concentrations of 138±9 mg/dL at baseline were allocated to treatment with placebo (14 patients) or 40 mg/d pravastatin (13 patients) in a randomized, double-blind, prospective trial. Coronary endothelial function was assessed before and 24 hours after single treatment by quantitative coronary angiography during intracoronary infusion of nitroglycerin or increasing concentrations of acetylcholine (0.01, 0.1, and 1 μmol/L). Coronary blood flow reserve was measured by Doppler velocimetry during adenosine infusion. Intracoronary acetylcholine infusion induced abnormal vasoconstriction in both groups before treatment, indicating coronary endothelial dysfunction. Treatment with a single oral 40-mg dose of pravastatin significantly attenuated acetylcholine-mediated vasoconstriction after 24 hours (mean±SE decrease in luminal diameter before and after treatment: 0.01 μmol/L, 6.1±2.2% versus 3.0±1.2%; 0.1 μmol/L, 15.6±2.6% versus 7.4±1.8%; P <0.05; 1 μmol/L, 22.9±2.9% versus 13.2±2.6%; P <0.05). There was no significant difference in the response to acetylcholine in the placebo group (8.1±2.4% versus 9.7±2.4%, 16.1±2.9% versus 16.8±3.2%, and 21.4±3.9% versus 23.3±4.2%). The response to nitroglycerin infusion was not altered in both groups. Increase in coronary blood flow in response to adenosine and coronary flow reserve remained unchanged during placebo and statin treatment. Serum concentrations of blood lipids and high-sensitive C-reactive protein were not significantly altered after 24 hours in response to placebo or pravastatin therapy. Statin treatment improves endothelium-dependent coronary vasomotion within 24 hours in the absence of significant cholesterol reduction. The full text of this article is available online at http://www.circresaha.org.