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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1471.)
© 2007 American Heart Association, Inc.

Thrombosis

Fluvastatin Alters Platelet Aggregability in Patients With Hypercholesterolemia

Possible Improvement of Intraplatelet Redox Imbalance via HMG-CoA Reductase

Nobuya Haramaki; Hisao Ikeda; Katsuhiko Takenaka; Atsushi Katoh; Ryo Sugano; Sho-ichi Yamagishi; Hidehiro Matsuoka; Tsutomu Imaizumi

From the Division of Cardiovascular Medicine, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.

Correspondence to Hisao Ikeda, MD, PhD, Division of Cardiovascular Medicine, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan. E-mail ikeda_hisao{at}kurume-u.ac.jp

Background— Hypercholesterolemia enhances platelet aggregability. Statins have beneficial effects on cardiovascular events. The purpose of this study is to investigate whether statins inhibit platelet aggregation and, if so, the mechanisms.

Methods and Results— Twelve patients with hypercholesterolemia were prospectively randomized in a crossover design to receive either fluvastatin (20 mg/d) or colestimide (3000 mg/d) for 12 weeks. The subjects were switched to the opposite arm for additional 12 weeks. Before and after first and second treatments, experiments were performed. Eleven age-matched volunteers with normal lipid profiles served as controls. ADP-induced platelet aggregation, platelet-derive nitric oxide (PDNO) release, intraplatelet levels of GSH and GSSG, and intraplatelet nitrotyrosine production during platelet aggregation were measured. Fluvastatin and colestimide equally lowered total and low density lipoprotein cholesterol levels in hypercholesterolemia. Platelet aggregation was greater in hypercholesterolemia than in normocholesterolemia before treatment and was altered by fluvastatin. PDNO release, intraplatelet glutathione level, and GSH/GSSG ratio were lower in hypercholesterolemia than in normocholesterolemia before treatment and were increased by fluvastatin. Intraplatelet nitrotyrosine formation was greater in hypercholesterolemia than in normocholesterolemia, and decreased by fluvastatin. Colestimide did not have such effects. In vitro application of fluvastatin dose-dependently inhibited platelet aggregation. Furthermore, in vitro application of fluvastatin dose-dependently inhibited platelet nitrotyrosine expressions and the inhibitory effects by fluvastatin were reversed by preincubation with geranylgeranylpyrophosphate.

Conclusions— Fluvastatin altered platelet aggregability in hypercholesterolemic patients in a cholesterol-lowering independent manner, which was partly mediated by the improvement of intraplatelet redox imbalance.

This study examined whether statins inhibit platelet aggregation. Twelve patients with hypercholesterolemia were randomized in a crossover design to receive either fluvastatin or colestimide for 12 weeks. Fluvastatin altered platelet aggregability in hypercholesterolemic patients in a cholesterol-lowering independent manner, which was partly mediated by the improvement of intraplatelet redox imbalance.

Key Words: lipids • platelets • aggregation • redox • statins

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