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(Circulation. 1999;99:3227-3233.)
© 1999 American Heart Association, Inc.

Clinical Investigation and Reports

Cholesterol Reduction Rapidly Improves Endothelial Function After Acute Coronary Syndromes

The RECIFE (Reduction of Cholesterol in Ischemia and Function of the Endothelium) Trial

Jocelyn Dupuis, MD, PhD; Jean-Claude Tardif, MD; Peter Cernacek, MD; Pierre Théroux, MD

From the Department of Medicine and Research Centre, Montreal Heart Institute, Montreal, Quebec, Canada.

Correspondence to Dr Jocelyn Dupuis, Research Centre, Montreal Heart Institute, 5000 Bélanger Street East, Montreal, Quebec H1T 1C8, Canada. E-mail dupuisj{at}icm.umontreal.ca

Background—Cholesterol lowering reduces coronary events. One mechanism could be improvement of endothelial function. In line with this hypothesis, this study investigates whether cholesterol reduction can result in rapid improvement of endothelial function after acute coronary syndromes.

Methods and Results—Patients with acute myocardial infarction or unstable angina and total cholesterol levels at admission 5.2 mmol/L or LDL 3.4 mmol/L were randomized to placebo (n=30) or pravastatin 40 mg daily (n=30) for 6 weeks. Brachial ultrasound was used to measure endothelium-dependent flow-mediated dilatation (FMD) and response to endothelium-independent nitroglycerin. Changes in the levels of markers of platelet activation, coagulation factors, and plasma endothelin levels were also assessed. Total and LDL cholesterol levels were similar at admission and before randomization in both groups. With pravastatin, but not with placebo, they decreased by 23% (P<0.05) and 33% (P<0.01), respectively. FMD was unchanged with placebo, 5.43±0.74% (mean±SEM) to 5.84±0.81%, but increased with pravastatin, 4.93±0.81% to 7.0±0.79% (P=0.02), representing a 42% relative increase. Responses to nitroglycerin were similar during the time course of the study in the 2 groups. Markers of platelet activity, coagulation factors, and endothelin levels were not affected by pravastatin.

Conclusions—Cholesterol reduction with pravastatin initiated early after acute coronary syndromes rapidly improves endothelial function after 6 weeks of therapy.

Key Words: coronary disease • cholesterol • endothelium • risk factors

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				S. Vehkavaara, T. Hakala-Ala-Pietila, A. Virkamaki, R. Bergholm, C. Ehnholm, O. Hovatta, M.-R. Taskinen, and H. Yki-Jarvinen Differential Effects of Oral and Transdermal Estrogen Replacement Therapy on Endothelial Function in Postmenopausal Women Circulation, November 28, 2000; 102(22): 2687 - 2693. [Abstract] [Full Text] [PDF]

				M. Shechter, M. Sharir, M. J. P. Labrador, J. Forrester, B. Silver, and C. N. Bairey Merz Oral Magnesium Therapy Improves Endothelial Function in Patients With Coronary Artery Disease Circulation, November 7, 2000; 102(19): 2353 - 2358. [Abstract] [Full Text] [PDF]

				L. M. Title, P. M. Cummings, K. Giddens, J. J. Genest Jr, and B. A. Nassar Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease J. Am. Coll. Cardiol., September 1, 2000; 36(3): 758 - 765. [Abstract] [Full Text] [PDF]

				J. A. Vita, A. C. Yeung, M. Winniford, J. M. Hodgson, C. B. Treasure, J. L. Klein, S. Werns, M. Kern, D. Plotkin, W. J. Shih, et al. Effect of Cholesterol-Lowering Therapy on Coronary Endothelial Vasomotor Function in Patients With Coronary Artery Disease Circulation, August 22, 2000; 102(8): 846 - 851. [Abstract] [Full Text] [PDF]

				D. Waters Cholesterol Lowering : Should It Continue to Be the Last Thing We Do? Circulation, June 29, 1999; 99(25): 3215 - 3217. [Full Text] [PDF]

				A. W. Chan, D. L. Bhatt, D. P. Chew, M. J. Quinn, D. J. Moliterno, E. J. Topol, and S. G. Ellis Early and Sustained Survival Benefit Associated With Statin Therapy at the Time of Percutaneous Coronary Intervention Circulation, February 12, 2002; 105(6): 691 - 696. [Abstract] [Full Text] [PDF]

				K. Yokoyama, T. Ishibashi, H. Ohkawara, J. Kimura, I. Matsuoka, T. Sakamoto, K. Nagata, K. Sugimoto, S. Sakurada, and Y. Maruyama HMG-CoA Reductase Inhibitors Suppress Intracellular Calcium Mobilization and Membrane Current Induced by Lysophosphatidylcholine in Endothelial Cells Circulation, February 26, 2002; 105(8): 962 - 967. [Abstract] [Full Text] [PDF]