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(Circulation. 2001;103:1942.)
© 2001 American Heart Association, Inc.

Clinical Investigation and Reports

Fluvastatin Lowers Atherogenic Dense Low-Density Lipoproteins in Postmenopausal Women With the Atherogenic Lipoprotein Phenotype

Winfried März, MD; Hubert Scharnagl, BSc; Claudia Abletshauser, MD; Michael M. Hoffmann, PhD; Aloys Berg, MD; Joseph Keul, MD; Heinrich Wieland, MD; Manfred W. Baumstark, PhD

From the Division of Clinical Chemistry (W.M., H.S., M.M.H., H.W.) and the Division of Sports Medicine, Department of Medicine (A.B., J.K., M.W.B.), Albert Ludwigs-University, Freiburg, Germany; and Novartis Pharma AG, Nürnberg, Germany (C.A.).

Correspondence to Winfried März, MD, Department of Medicine, Hugstetter Straße 55, D-79106 Freiburg, Germany. E-mail maerz{at}med1.ukl.uni-freiburg.de

Background—Although HMG-CoA reductase inhibitors (HMGRIs) are effective lipid-lowering agents, it remains controversial whether these agents also lower dense LDL (dLDL), a predominance of which is considered to contribute to the atherogenicity of the metabolic syndrome.

Methods and Results—In a multicenter, double-blind, randomized, placebo-controlled study, we determined the effect of the HMGRI fluvastatin on lipids, apolipoproteins, and LDL subfractions (by equilibrium density gradient ultracentrifugation). A total of 52 postmenopausal women with combined hyperlipidemia and increased dLDL were treated with either fluvastatin 40 mg/d (n=35) or placebo (n=17). After 12 weeks’ treatment, significant reductions (P<0.001) in total cholesterol (-19%), IDL cholesterol (-35%), LDL cholesterol (-23%), apolipoprotein B (-21%), and apolipoprotein B in dLDL (-42%) were apparent among fluvastatin recipients. No significant changes in triglycerides or HDL cholesterol were observed. The effect of fluvastatin on dLDL was correlated with baseline values. There was no consistent relationship, however, between the effect of fluvastatin on triglycerides and the decrease in dLDL.

Conclusions—Fluvastatin lowers total and LDL cholesterol and the concentration of dLDL. This profile may contribute to an antiatherogenic effect for fluvastatin that is greater than expected on the basis of changes in lipids and apolipoproteins.

Key Words: fluvastatin • coronary disease • lipoproteins

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