Circulation. 2002;106:399-402
Published online before print July 1, 2002, doi: 10.1161/01.CIR.0000025419.95769.F0
Published online before print July 1, 2002, doi: 10.1161/01.CIR.0000025419.95769.F0
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(Circulation. 2002;106:399.)
© 2002 American Heart Association, Inc.
Brief Rapid Communications |
Association Between Enhanced Soluble CD40L and Prothrombotic State in Hypercholesterolemia
Effects of Statin Therapy
From the Center of Excellence on Aging (E.P., C.D.F., M.N., A.F., F.C., G.D.), Center for the Prevention of Atherosclerosis (F.C., A.M., M.F.), University of Chieti "G. D’Annunzio" School of Medicine, Chieti, Italy.
Correspondence to Giovanni Davì, MD, Dipartimento di Medicina e Scienze dell’Invecchiamento, via dei Vestini 31, 66013 Chieti, Italy. E-mail gdavi{at}unich.it
Background— Hypercholesterolemia is associated with inflammation and the prothrombotic state. CD40-CD40 ligand (CD40L) interactions promote a prothrombotic response in nucleated cells. The aim of this study was to characterize the in vivo expression of soluble CD40L (sCD40L) in hypercholesterolemia, to correlate it with the extent of the prothrombotic state, and to investigate whether it may be modified by statins.
Methods and Results— We studied 80 hypercholesterolemic patients and 80 matched healthy subjects. Hypercholesterolemic subjects had enhanced levels of sCD40L, factor VIIa (FVIIa), and prothrombin fragment 1+2 (F1+2) compared with healthy subjects. sCD40L correlated with total cholesterol and LDL cholesterol. Moreover, sCD40L was positively associated with in vivo platelet activation, as reflected by plasma P-selectin and urinary 11-dehydro-thromboxane B2, and with procoagulant state, as reflected by FVIIa and F1+2. Inhibition of cholesterol biosynthesis by pravastatin or cerivastatin was associated with comparable, significant reductions in sCD40L, FVIIa, and F1+2.
Conclusions— This study suggests that sCD40L may represent the molecular link between hypercholesterolemia and the prothrombotic state and demonstrates that statin therapy may significantly reduce sCD40L and the prothrombotic state.
Key Words: risk factors • atherosclerosis • hypercholesterolemia • inflammation
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