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

Abstract

BACKGROUND:

The short-term effects of hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) on endothelial function at doses that do not affect 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 function 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 cerivastatin treatment (0.15 mg/d) for 3 days. Endothelium-dependent flow-mediated dilatation, endothelium-independent dilatation by nitroglycerin in the brachial artery, nitric oxide-related products (nitrite/nitrate and cGMP), endothelium-related products (von Willebrand Factor, soluble vascular cell adhesion molecule-1, and soluble intercellular adhesion molecule-1), and a marker of oxidant stress (8-isoprostane) were assessed. Levels of plasma lipids were not changed before and after treatment with cerivastatin. Flow-mediated dilatation was significantly increased by cerivastatin treatment, as were plasma nitrite/nitrate levels (from 16.9+/-3.4 to 22.0+/-3.7 micromol/L, P<0.05) and cGMP values. The percent of nitroglycerin-induced dilatation was not changed. Plasma concentrations of 8-isoprostane decreased, and levels of soluble vascular cell adhesion molecule also tended to decrease with cerivastatin.

CONCLUSIONS:

Improvement of endothelial function was in line with antiatherosclerotic effects. Cerivastatin improved impaired endothelial function in the short-term without affecting lipid profiles in elderly diabetic patients. This effect may be partly due to upregulation of endothelial nitric oxide synthase.

• Authors: T Tsunekawa, T Hayashi, H Kano, D Sumi, H Matsui-Hirai, N K Thakur, K Egashira, A Iguchi
• Journal: Circulation (Circulation) Vol. 104 Issue 4 Pg. 376-9 (Jul 24 2001) ISSN: 1524-4539 [Electronic] United States
• PMID: 11468195 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Lipids
• Nitrates
• Nitrites
• Pyridines
• cerivastatin
• Cyclic GMP

Topics

• Aged
• Brachial Artery (drug effects, physiology)
• Cyclic GMP (blood)
• Diabetes Complications
• Diabetes Mellitus (drug therapy, physiopathology)
• Endothelium, Vascular (drug effects, physiopathology)
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology, therapeutic use)
• Hypercholesterolemia (blood, complications)
• Lipids (blood)
• Male
• Nitrates (blood)
• Nitrites (blood)
• Pyridines (pharmacology, therapeutic use)
• Time Factors
• Treatment Outcome
• Vasodilation (drug effects)