(Circulation. 1997;95:1126-1131.)
© 1997 American Heart Association, Inc.
Articles |
Simvastatin, an HMG–Coenzyme A Reductase Inhibitor, Improves Endothelial Function Within 1 Month
the Department of Cardiology and Medicine, Royal Perth (Australia) Hospital and the Department of Human Movement, University of Western Australia, Perth (D.G.).
Correspondence to Gerard O'Driscoll, Department of Cardiology, Royal Perth Hospital, Wellington St, Perth, Western Australia 6000.
Background Cholesterol-lowering therapy can improve cardiovascular morbidity and mortality in patients with atherosclerosis. Although the mechanisms responsible are unclear, these benefits precede macroscopic changes in the vasculature. Emerging evidence that improvement in endothelial function may occur requires substantiation; in particular, it is unclear how early any such improvement would be detectable after initiation of therapy.
Methods and Results This randomized, double-blind, placebo-controlled crossover study evaluated the effect of simvastatin (20 mg daily for 4 weeks) on endothelium-dependent and endothelium-independent vasodilation and on the response to the inhibitor of nitric oxide synthesis, NG-monomethyl-L-arginine (L-NMMA), in the forearm vasculature of subjects with moderate elevation of total serum cholesterol (6.0 to 10.0 mmol/L) by use of strain-gauge plethysmography. Studies were repeated after 3 more months of open therapy. When the results are expressed as percentage changes in flow in the infused arm relative to the noninfused arm, the vasodilator response to acetylcholine was significantly increased after 4 weeks of treatment with simvastatin (P<.0005), and this improvement was further enhanced after 3 months (P<.005). Concurrently, simvastatin augmented the vasoconstrictor response to L-NMMA, an effect that was maintained at 3 months (P<.0005). The response to the endothelium-independent vasodilator sodium nitroprusside was unaltered.
Conclusions These observations indicate that within 1 month of treatment with simvastatin, both the stimulated and basal nitric oxide dilator functions of the endothelium are augmented, and the benefits of this HMG–coenzyme A reductase inhibitor persist with continued therapy.
Key Words: blood flow • cholesterol • endothelium • hypercholesterolemia
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P. Di Napoli, A.A. Taccardi, M. Oliver, and R. De Caterina Statins and stroke: evidence for cholesterol-independent effects Eur. Heart J., December 2, 2002; 23(24): 1908 - 1921. [PDF]
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V. Schachinger and A. M. Zeiher Atherogenesis--recent insights into basic mechanisms and their clinical impact Nephrol. Dial. Transplant., December 1, 2002; 17(12): 2055 - 2064. [Full Text] [PDF]
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M. J. McGirt, J. R. Lynch, A. Parra, H. Sheng, R. D. Pearlstein, D. T. Laskowitz, D. A. Pelligrino, and D. S. Warner Simvastatin Increases Endothelial Nitric Oxide Synthase and Ameliorates Cerebral Vasospasm Resulting From Subarachnoid Hemorrhage Stroke, December 1, 2002; 33(12): 2950 - 2956. [Abstract] [Full Text] [PDF]
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 T. Nishimura, J. L. Faul, G. J. Berry, L. T. Vaszar, D. Qiu, R. G. Pearl, and P. N. Kao Simvastatin Attenuates Smooth Muscle Neointimal Proliferation and Pulmonary Hypertension in Rats Am. J. Respir. Crit. Care Med., November 15, 2002; 166(10): 1403 - 1408. [Abstract] [Full Text] [PDF]
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D. J. Lefer Statins as Potent Antiinflammatory Drugs Circulation, October 15, 2002; 106(16): 2041 - 2042. [Full Text] [PDF]
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D. Pruefer, J. Makowski, M. Schnell, U. Buerke, M. Dahm, H. Oelert, U. Sibelius, U. Grandel, F. Grimminger, W. Seeger, et al. Simvastatin Inhibits Inflammatory Properties of Staphylococcus aureus{alpha}-Toxin Circulation, October 15, 2002; 106(16): 2104 - 2110. [Abstract] [Full Text] [PDF]
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D Patterson, J B C Dick, and A D Struthers Intensive statin treatment improves baroreflex sensitivity: another cardioprotective mechanism for statins? Heart, October 1, 2002; 88(4): 415 - 416. [Full Text] [PDF]
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A. C. Sposito and M. J. Chapman Statin Therapy in Acute Coronary Syndromes: Mechanistic Insight Into Clinical Benefit Arterioscler Thromb Vasc Biol, October 1, 2002; 22(10): 1524 - 1534. [Abstract] [Full Text] [PDF]
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 R. S. Wright, J. G. Murphy, K. A. Bybee, S. L. Kopecky, and J.-M. LaBlanche Statin Lipid-Lowering Therapy for Acute Myocardial Infarction and Unstable Angina: Efficacy and Mechanism of Benefit Mayo Clin. Proc., October 1, 2002; 77(10): 1085 - 1092. [Abstract] [PDF]
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G. K. Sukhova, J. K. Williams, and P. Libby Statins Reduce Inflammation in Atheroma of Nonhuman Primates Independent of Effects on Serum Cholesterol Arterioscler Thromb Vasc Biol, September 1, 2002; 22(9): 1452 - 1458. [Abstract] [Full Text] [PDF]
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D. Green, C. Cheetham, L. Mavaddat, K. Watts, M. Best, R. Taylor, and G. O'Driscoll Effect of lower limb exercise on forearm vascular function: contribution of nitric oxide Am J Physiol Heart Circ Physiol, September 1, 2002; 283(3): H899 - H907. [Abstract] [Full Text] [PDF]
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C. S. Hayward, M. Kraidly, C. M. Webb, and P. Collins Assessment of endothelial function using peripheral waveform analysis: A clinical application J. Am. Coll. Cardiol., August 7, 2002; 40(3): 521 - 528. [Abstract] [Full Text] [PDF]
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H. R. Hellstrom Coronary microvascular spasm in patients with vasospastic angina J. Am. Coll. Cardiol., August 7, 2002; 40(3): 573 - 574. [Full Text] [PDF]
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K. Bates, C. E. Ruggeroli, S. Goldman, and M. A. Gaballa Simvastatin restores endothelial NO-mediated vasorelaxation in large arteries after myocardial infarction Am J Physiol Heart Circ Physiol, August 1, 2002; 283(2): H768 - H775. [Abstract] [Full Text] [PDF]
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C. Vecchione and R. P. Brandes Withdrawal of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors Elicits Oxidative Stress and Induces Endothelial Dysfunction in Mice Circ. Res., July 26, 2002; 91(2): 173 - 179. [Abstract] [Full Text] [PDF]
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 M. A. Sardo, M. Castaldo, M. Cinquegrani, M. Bonaiuto, A. Maesano, A. Versace, M. Spadaro, S. Campo, G. Nicocia, D. Altavilla, et al. Effects of Atorvastatin Treatment on sICAM-1 and Plasma Nitric Oxide Levels in Hypercholesterolemic Subjects Clinical and Applied Thrombosis/Hemostasis, July 1, 2002; 8(3): 257 - 263. [Abstract] [PDF]
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F. V. van Venrooij, M. A. van de Ree, M. L. Bots, R. P. Stolk, M. V. Huisman, and J. D. Banga Aggressive Lipid Lowering Does Not Improve Endothelial Function in Type 2 Diabetes: The Diabetes Atorvastatin Lipid Intervention (DALI) Study: a randomized, double-blind, placebo-controlled trial Diabetes Care, July 1, 2002; 25(7): 1211 - 1216. [Abstract] [Full Text] [PDF]
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J. R. Sowers Endothelial Vasodilation Effects of Statins in Type 2 Diabetic Patients : Response to van Venrooij et al. Diabetes Care, July 1, 2002; 25(7): 1242 - 1243. [Full Text] [PDF]
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L. K. Newby, A. Kristinsson, M. V. Bhapkar, P. E. Aylward, A. P. Dimas, W. W. Klein, D. K. McGuire, D. J. Moliterno, F. W. A. Verheugt, W. D. Weaver, et al. Early Statin Initiation and Outcomes in Patients With Acute Coronary Syndromes JAMA, June 19, 2002; 287(23): 3087 - 3095. [Abstract] [Full Text] [PDF]
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 J. R Chiong and A. B Miller Review: Renin-angiotensin system antagonism and lipid-lowering therapy in cardiovascular risk management Journal of Renin-Angiotensin-Aldosterone System, June 1, 2002; 3(2): 96 - 102. [Abstract] [PDF]
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H. Krum and J. J. McMurray Statins and chronic heart failure: do we need a large-scale outcome trial? J. Am. Coll. Cardiol., May 15, 2002; 39(10): 1567 - 1573. [Abstract] [Full Text] [PDF]
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K. E. Ferrier, M. H. Muhlmann, J.-P. Baguet, J. D. Cameron, G. L. Jennings, A. M. Dart, and B. A. Kingwell Intensive cholesterol reduction lowers blood pressure and large artery stiffness in isolated systolic hypertension J. Am. Coll. Cardiol., March 20, 2002; 39(6): 1020 - 1025. [Abstract] [Full Text] [PDF]
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S. Wassmann, U. Laufs, K. Muller, C. Konkol, K. Ahlbory, A. T. Baumer, W. Linz, M. Bohm, and G. Nickenig Cellular Antioxidant Effects of Atorvastatin In Vitro and In Vivo Arterioscler Thromb Vasc Biol, February 1, 2002; 22(2): 300 - 305. [Abstract] [Full Text] [PDF]
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