Atherosclerosis 153 (2000) 181 – 189 Statins and cardiovascular diseases: the multiple effects of lipid-lowering therapy by statins U. Rauch a,b , J.I. Osende a,b , J.H. Chesebro b , V. Fuster b , D.A. Vorchheimer b , K. Harris b , P. Harris b , D.A. Sandler b , J.T. Fallon b,c , S. Jayaraman a , J.J. Badimon a,b, * a The Cardioascular Biology Research Laboratory, The Zena and Michael A. Wiener Cardioascular Institute, Mount Sinai School Of Medicine, One GustaeL. Ley Place, Box 1030, New York, NY-10029, USA b The Zena and Michael A. Wiener Cardioascular Institute, New York NY-10029, USA c Department of Pathology, Mount Sinai School of Medicine, New York NY-10029, USA Received 12 October 1999; received in revised form 20 December 1999; accepted 19 January 2000 Abstract Cholesterol lowering involving different therapies improves the clinical outcome of patients. To define the underlying pathomechanism, we studied whether treatment with statins was associated with changes in blood thrombogenicity, endothelial dysfunction and soluble adhesion molecule levels. Fifty hypercholesterolemic patients were treated with pravastatin (40 mg/day, n =24) or simvastatin (20 mg/day, n =26). Lipid profile and blood thrombogenicity were assessed in all patients before and after 3 months of cholesterol reducing therapy. Blood thrombogenicity was assessed as thrombus formation, perfusing non-anticoagu- lated blood directly from the patients’ vein through the Badimon perfusion chamber (shear rate 1690/s). Endothelial-dependent vasomotor response was tested by laser-Doppler flowmeter. Soluble adhesion molecule level were measured by ELISA. Total and LDL cholesterol were reduced in the two treatment groups by statin therapy. Statin therapy was associated with a significant reduction in blood thrombogenicity and endothelium-dependent vasoresponse. No differences were observed between simvastatin or pravastatin treatment. Lipid lowering by statins had no effect on plasma levels of fibrinogen, sL-selectin, sP-selectin and sICAM-1 antigen. Cholesterol lowering by both statins reduced the increased blood reactivity and endothelial dysfunction present under hypercholesterolemia. The multiple effects of lipid lowering therapy by statins may explain the benefits observed in recent epidemiological trials. © 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Statin; Hyperlipidemia; Thrombosis; Endothelium; Atherosclerosis www.elsevier.com/locate/atherosclerosis 1. Introduction Hypercholesterolemia — the major risk factors for the development of atherosclerotic disease [1 – 4] is asso- ciated with increased deposition of lipids and mono- cytes/macrophages within the arterial wall, endothelial dysfunction and vasoconstriction, enhanced platelet re- activity, and hypercoagulability [5,6]. Reduction of serum cholesterol levels by different interventions in- cluding diet, exercise, lifestyle changes or pharmacolog- ical approaches is associated with a significant reduction in cardiovascular mortality and morbidity [3–6]. Recently, the effectiveness of a new class of powerful hypolipidemic agents, the statins, has been tested in several large clinical trials. These trials showed significant improvement in clinical outcomes of patients with and without coronary artery disease [7 – 12]. These observations were applicable to primary and secondary prevention of coronary events in both, hyper- and normocholesterolemic populations [4,6 – 12]. Statin treatment was associated with a consistent reduction in coronary events of 30 – 40% [13,14]. Angiographic trials assessing the effect of lipid lower- ing treatment on coronary atherosclerosis showed only a small reduction in coronary stenosis [14,15]. The clinical benefits observed in these trials significantly * Corresponding author. Tel.: +1-212-2418484; fax: +1-212- 4266962. E-mail address: jbadimo@smtplink.mssm.edu (J.J. Badimon). 0021-9150/00/$ - see front matter © 2000 Elsevier Science Ireland Ltd. All rights reserved. PII:S0021-9150(00)00397-X