Cerivastatin, a hydroxymethylglutaryl coenzyme A reductase inhibitor, improves endothelial function in elderly diabetic patients within 3 days

Background-The short-term effects of hydroxymethylglutaryl coenzyme A reduc tase inhibitors (statins) on endothelial function at doses that do not affe ct plasma lipid levels are not known. Methods and Results-We investigated the short-term effects of cerivastatin, a hydroxymethylglutaryl coenzyme A reductase inhibitor, on endothelial fun ction and endothelium-related products in elderly diabetic patients. Twenty -seven elderly diabetic patients (aged 69.3 +/-3.4 years), with or without mild hypercholesterolemia, were enrolled in this study, which tested ceriva statin treatment (0.15 mg/d) for 3 days. Endothelium-dependent flow-mediate d dilatation, endothelium-independent dilatation by nitroglycerin in the br achial artery, nitric oxide-related products (nitrite/nitrate and cGMP), en dothelium-related products (von Willebrand Factor, soluble vascular cell ad hesion molecule-1, and soluble intercellular adhesion molecule-1), and a ma rker of oxidant stress (8-isoprostane) were, assessed. Levels of plasma lip ids were not changed before and after treatment with cerivastatin. Flow-med iated dilatation was significantly increased by cerivastatin treatment, as were plasma nitrite/nitrate levels (from 16.9 +/-3.4 to 22.0 +/-3.7 mu mol/ L, P<0.05) and cGMP values. The percent of nitroglycerin-induced dilatation was not changed. Plasma concentrations of 8-isoprostane decreased, and lev els of soluble vascular cell adhesion molecule also tended to decrease with cerivastatin. Conclusions-Improvement of endothelial function was in line with antiathero sclerotic effects. Cerivastatin improved impaired endothelial function in t he short-term without affecting lipid profiles in elderly diabetic patients . This effect may be partly due to upregulation of endothelial nitric oxide synthase.