Published online before print October 9, 2003, doi: 10.1161/01.RES.0000099503.13312.7B
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on August 7, 2003
Revised on September 9, 2003
Accepted on September 25, 2003
Rapid Effect of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibition on Coronary Endothelial Function
Sven Wassmann ;
From Medizinische Klinik und Poliklinik, Innere Medizin III, Universitätskliniken des Saarlandes, Homburg/Saar, Germany.
* To whom correspondence should be addressed. E-mail: nickenig{at}med-in.uni-saarland.de.
Treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) decreases cardiovascular event rates in hypercholesterolemic patients. Whether statins exert effects within 24 hours on the coronary vasculature in patients with endothelial dysfunction has not been elucidated. Twenty-seven patients with stable angina pectoris and average low-density lipoprotein cholesterol concentrations of 138±9 mg/dL at baseline were allocated to treatment with placebo (14 patients) or 40 mg/d pravastatin (13 patients) in a randomized, double-blind, prospective trial. Coronary endothelial function was assessed before and 24 hours after single treatment by quantitative coronary angiography during intracoronary infusion of nitroglycerin or increasing concentrations of acetylcholine (0.01, 0.1, and 1 µmol/L). Coronary blood flow reserve was measured by Doppler velocimetry during adenosine infusion. Intracoronary acetylcholine infusion induced abnormal vasoconstriction in both groups before treatment, indicating coronary endothelial dysfunction. Treatment with a single oral 40-mg dose of pravastatin significantly attenuated acetylcholine-mediated vasoconstriction after 24 hours (mean±SE decrease in luminal diameter before and after treatment: 0.01 µmol/L, 6.1±2.2% versus 3.0±1.2%; 0.1 µmol/L, 15.6±2.6% versus 7.4±1.8%; P<0.05; 1 µmol/L, 22.9±2.9% versus 13.2±2.6%; P<0.05). There was no significant difference in the response to acetylcholine in the placebo group (8.1±2.4% versus 9.7±2.4%, 16.1±2.9% versus 16.8±3.2%, and 21.4±3.9% versus 23.3±4.2%). The response to nitroglycerin infusion was not altered in both groups. Increase in coronary blood flow in response to adenosine and coronary flow reserve remained unchanged during placebo and statin treatment. Serum concentrations of blood lipids and high-sensitive C-reactive protein were not significantly altered after 24 hours in response to placebo or pravastatin therapy. Statin treatment improves endothelium-dependent coronary vasomotion within 24 hours in the absence of significant cholesterol reduction. The full text of this article is available online at http://www.circresaha.org.
Key words: endothelial function • statins • coronary disease • acetylcholine • angiography
This article has been cited by other articles:
 |
|
 |
|
  A. Nusca, R. Melfi, and G. Di Sciascio Review: Percutaneous coronary interventions and statins therapy Therapeutic Advances in Cardiovascular Disease, April 1, 2008; 2(2): 101 - 107. [Abstract] [PDF]
|
|
|
|
 |
|
 X. Sun and D. D. Ku Rosuvastatin provides pleiotropic protection against pulmonary hypertension, right ventricular hypertrophy, and coronary endothelial dysfunction in rats Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H801 - H809. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Mangat, S. Agarwal, and C. Rosendorff Do Statins Lower Blood Pressure? Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2007; 12(2): 112 - 123. [Abstract] [PDF]
|
|
|
|
 |
|
 G. Patti, V. Pasceri, G. Colonna, M. Miglionico, D. Fischetti, G. Sardella, A. Montinaro, and G. Di Sciascio Atorvastatin Pretreatment Improves Outcomes in Patients With Acute Coronary Syndromes Undergoing Early Percutaneous Coronary Intervention: Results of the ARMYDA-ACS Randomized Trial J. Am. Coll. Cardiol., March 27, 2007; 49(12): 1272 - 1278. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. N. Boushra and M. Muntazar Review article: The role of statins in reducing perioperative cardiac risk: physiologic and clinical perspectives: [Le role des statines dans la reduction du risque cardiaque perioperatoire : perspectives physiologiques et cliniques]. Can J Anesth, November 1, 2006; 53(11): 1126 - 1147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Fichtlscherer, C. Schmidt-Lucke, S. Bojunga, L. Rossig, C. Heeschen, S. Dimmeler, and A. M. Zeiher Differential effects of short-term lipid lowering with ezetimibe and statins on endothelial function in patients with CAD: clinical evidence for 'pleiotropic' functions of statin therapy Eur. Heart J., May 2, 2006; 27(10): 1182 - 1190. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Werner, S. Wassmann, P. Ahlers, S. Kosiol, and G. Nickenig Circulating CD31+/Annexin V+ Apoptotic Microparticles Correlate With Coronary Endothelial Function in Patients With Coronary Artery Disease Arterioscler. Thromb. Vasc. Biol., January 1, 2006; 26(1): 112 - 116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Schafer, D. Fraccarollo, M. Eigenthaler, P. Tas, A. Firnschild, S. Frantz, G. Ertl, and J. Bauersachs Rosuvastatin Reduces Platelet Activation in Heart Failure: Role of NO Bioavailability Arterioscler. Thromb. Vasc. Biol., May 1, 2005; 25(5): 1071 - 1077. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Pasceri, G. Patti, A. Nusca, C. Pristipino, G. Richichi, G. Di Sciascio, and on behalf of the ARMYDA Investigators Randomized Trial of Atorvastatin for Reduction of Myocardial Damage During Coronary Intervention: Results From the ARMYDA (Atorvastatin for Reduction of MYocardial Damage during Angioplasty) Study Circulation, August 10, 2004; 110(6): 674 - 678. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P.J. Halcox and J. E. Deanfield Beyond the Laboratory: Clinical Implications for Statin Pleiotropy Circulation, June 1, 2004; 109(21_suppl_1): II-42 - II-48. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. B. Hussain, S. Singhal, H. S. Markus, and D. R.J. Singer Abnormal Vasoconstrictor Responses to Angiotensin II and Noradrenaline in Isolated Small Arteries From Patients With Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL) Stroke, April 1, 2004; 35(4): 853 - 858. [Abstract] [Full Text] [PDF]
|
|