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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:1524.)
© 2005 American Heart Association, Inc.

Letters to the Editor

Simvastatin Given for 3 Days Can Inhibit Thrombin Generation and Activation of Factor V and Enhance Factor Va Inactivation in Hypercholesterolemic Patients

Anetta Undas; Magdalena Celinska-Löwenhoff; Kathleen E. Brummel-Ziedins; Jan Brozek; Andrew Szczeklik; Kenneth G. Mann

Department of Medicine (A.U., M.C.-L., J.B., A.S.) Jagiellonian University School of Medicine Krakow, Poland and the Department of Biochemistry (K.E.B.-Z., K.G.M.) University of Vermont, Burlington

An extract of the first 250 words of the full text is provided, because this article has no abstract.

To the Editor:

The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, have been reported to exert multiple cholesterol-independent actions, including inhibition of blood coagulation, most likely attributable to downregulation of tissue factor (TF) expression.¹ Previously, we have demonstrated that simvastatin inhibits blood clotting after a 3-month simvastatin therapy.² It is unknown how rapidly statin administration can influence thrombin formation, factor (F)V activation, and the proteolytic degradation of FVa. The aim of the current study was to assess early effects of statins on coagulant reactions.

Fourteen men (mean age, 54.6 years) with LDL cholesterol levels >3.4 mmol/L (130 mg/dL), who were treated with low-dose aspirin (75 mg/d), participated in the study after giving informed written consent. At baseline and after 3 days of simvastatin administration (40 mg/d), coagulant reactions were assessed in blood collected every 30 seconds at the site of microvascular injury, as previously described.^2,3 Using quantitative Western blotting, we evaluated the time-courses of FVa generation and FVa inactivation, along with thrombin formation. We also determined lipid profiles, C-reactive protein (CRP) levels, fibrinogen, and thrombin-antithrombin complexes (TAT) in peripheral venous blood (Dade Behring) with data expressed as mean±SEM. Paired t test and Wilcoxon signed ranks test were used when appropriate to compare the differences before and after simvastatin treatment. Spearman rank correlation coefficients were calculated to test the association between two variables.

A 3-day simvastatin administration significantly retarded prothrombin activation (P=0.002; Figure, A) and FVa heavy (P=0.027; Figure, B) and light chains (. . . [Full Text of this Article]

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