Association Between Enhanced Soluble CD40L and Prothrombotic State in Hypercholesterolemia Effects of Statin Therapy

• Published in: Circulation (New York, N.Y.) Vol. 106; no. 4; pp. 399 - 402
• Main Authors: Cipollone, Francesco, Mezzetti, Andrea, Porreca, Ettore, Di Febbo, Concetta, Nutini, Michele, Fazia, Maria, Falco, Angela, Cuccurullo, Franco, Davì, Giovanni
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 23.07.2002
• Subjects: Biological and medical sciences; CD40 Ligand - blood; Double-Blind Method; Factor VIIa - analysis; Female; General and cellular metabolism. Vitamins; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Hypercholesterolemia - blood; Hypercholesterolemia - drug therapy; Hypercholesterolemia - urine; Inflammation - blood; Inflammation - drug therapy; Male; Medical sciences; Middle Aged; P-Selectin - blood; Peptide Fragments - blood; Pharmacology. Drug treatments; Platelet Activation; Protein Precursors - blood; Prothrombin - analysis; Thromboxane B2 - analogs & derivatives; Thromboxane B2 - urine; Human; Prognosis; Enzyme; Hydroxymethylglutaryl-CoA synthase; Enzyme inhibitor; Cardiovascular disease; Metabolic diseases; Lipids; Hyperlipoproteinemia; Lyases; Inflammation; Factor VII; Oxo-acid-lyases; Vascular disease; Carbon-carbon lyases; Chemotherapy; Hypercholesterolemia; Treatment; Atherosclerosis; Prothrombin; Dyslipemia; Antilipemic agent
• ISSN: 0009-7322; 1524-4539; 1524-4539
• DOI: 10.1161/01.CIR.0000025419.95769.F0

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 B 2 , 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.