Circulation. 2002;106:1447-1452
Published online before print August 26, 2002, doi: 10.1161/01.CIR.0000029743.68247.31
Published online before print August 26, 2002, doi: 10.1161/01.CIR.0000029743.68247.31
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2002;106:1447.)
© 2002 American Heart Association, Inc.
Clinical Investigation and Reports |
Simvastatin Lowers C-Reactive Protein Within 14 Days
An Effect Independent of Low-Density Lipoprotein Cholesterol Reduction
From the Division of Endocrinology, Metabolism, and Diabetes (J.K.P., T.L.H., K.M.W., P.P., R.H.E.) and the Department of Preventive Medicine and Biometrics (G.K.G.), University of Colorado Health Sciences Center, Denver, Colo, and the Department of Medicine, Northwest Lipid Research Laboratories, University of Washington, Seattle, Wash (S.M.M.).
Correspondence to Robert H. Eckel, MD, Division of Endocrinology, Metabolism, and Diabetes, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Box B151, Denver, CO 80262. E-mail robert.eckel{at}uchsc.edu
Background— The early response of C-reactive protein to initiation of a hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) is not known. The purpose of this study was to determine the rate at which highly sensitive C-reactive protein (hsCRP) levels change after initiation of simvastatin and whether this occurs independently of the change in LDL cholesterol.
Methods and Results— The study was a crossover, double-blind design including 40 subjects with elevated LDL cholesterol. Subjects were randomly assigned to 1 of 2 groups: simvastatin 40 mg for 14 days, then placebo for 14 days, or placebo first, then simvastatin. Simvastatin decreased LDL cholesterol by 56±4 mg/dL (P<0.0001) at day 7 and by an additional 8±3 mg/dL (P=0.02) at day 14. Baseline log(hsCRP) levels were similar in the 2 groups. By day 14, log(hsCRP) was significantly lower in patients on simvastatin when compared with placebo (P=0.011). Although there was no significant difference in fibrinogen levels, simvastatin produced a modest increase in log[lipoprotein(a)] (P=0.03) at days 7 and 14. There were no relationships between the decrease in LDL cholesterol and the decrease in hsCRP.
Conclusions— Simvastatin lowers hsCRP by 14 days, independent of its effect on LDL cholesterol. This rapid impact of a statin on hsCRP has potential implications in the management of acute coronary syndromes.
Key Words: C-reactive protein • lipoproteins • fibrinogen • inflammation
This article has been cited by other articles:
 |
|
 |
|
  L. Fauchier, B. Pierre, A. de Labriolle, C. Grimard, N. Zannad, and D. Babuty Antiarrhythmic Effect of Statin Therapy and Atrial Fibrillation: A Meta-Analysis of Randomized Controlled Trials J. Am. Coll. Cardiol., February 26, 2008; 51(8): 828 - 835. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Lertsburapa, C. M. White, J. Kluger, O. Faheem, J. Hammond, and C. I. Coleman Preoperative statins for the prevention of atrial fibrillation after cardiothoracic surgery. J. Thorac. Cardiovasc. Surg., February 1, 2008; 135(2): 405 - 411. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Momin, N. Melikian, S. B. Wheatcroft, D. Grieve, L. C. John, A. El Gamel, M. T. Marrinan, J. B. Desai, C. Driver, R. Sherwood, et al. The association between saphenous vein endothelial function, systemic inflammation, and statin therapy in patients undergoing coronary artery bypass surgery J. Thorac. Cardiovasc. Surg., August 1, 2007; 134(2): 335 - 341. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Tanzer C-Reactive Protein Is Still a Potential Aid in Rheumatoid Arthritis Predictors Arch Intern Med, July 23, 2007; 167(14): 1552 - 1552. [Full Text] [PDF]
|
|
|
|
 |
|
 M.S. Kostapanos, E.N. Liberopoulos, J.A. Goudevenos, D.P. Mikhailidis, and M.S. Elisaf Do statins have an antiarrhythmic activity? Cardiovasc Res, July 1, 2007; 75(1): 10 - 20. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Ridker C-Reactive Protein and the Prediction of Cardiovascular Events Among Those at Intermediate Risk: Moving an Inflammatory Hypothesis Toward Consensus J. Am. Coll. Cardiol., May 29, 2007; 49(21): 2129 - 2138. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kinlay Low-Density Lipoprotein-Dependent and -Independent Effects of Cholesterol-Lowering Therapies on C-Reactive Protein: A Meta-Analysis J. Am. Coll. Cardiol., May 22, 2007; 49(20): 2003 - 2009. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kapiotis, G. Holzer, G. Schaller, M. Haumer, H. Widhalm, D. Weghuber, B. Jilma, G. Roggla, M. Wolzt, K. Widhalm, et al. A Proinflammatory State Is Detectable in Obese Children and Is Accompanied by Functional and Morphological Vascular Changes Arterioscler. Thromb. Vasc. Biol., November 1, 2006; 26(11): 2541 - 2546. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Zimmet and J. M. Hare Nitroso-Redox Interactions in the Cardiovascular System Circulation, October 3, 2006; 114(14): 1531 - 1544. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Suzuki, M. Saito, T. Nagai, H. Saeki, and Y. Kazatani Prevention of Positive Coronary Artery Remodeling with Statin Therapy in Patients with Coronary Artery Diseases Angiology, May 1, 2006; 57(3): 259 - 265. [Abstract] [PDF]
|
|
|
|
|
|
M. E. Marketou, E. A. Zacharis, D. Nikitovic, E. S. Ganotakis, F. I. Parthenakis, N. Maliaraki, and P. E. Vardas Early Effects of Simvastatin versus Atorvastatin on Oxidative Stress and Proinflammatory Cytokines in Hyperlipidemic Subjects Angiology, March 1, 2006; 57(2): 211 - 218. [Abstract] [PDF]
|
|
|
|
 |
|
 M. A. Arias, J. Sanchez-Gila, and D. Amar Obesity As a Risk Factor for Developing Postoperative Atrial Fibrillation Chest, March 1, 2006; 129(3): 828 - 829. [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Boos, R. A. Anderson, and G. Y.H. Lip Is atrial fibrillation an inflammatory disorder? Eur. Heart J., January 2, 2006; 27(2): 136 - 149. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-J. Li, C.-H. Fang, H.-Y. Qian, and W.-L. Hu Time Course of Rapid C-Reactive Protein Reduction by Pravastatin in Patients with Stable Angina Angiology, January 1, 2006; 57(1): 1 - 7. [Abstract] [PDF]
|
|
|
|
 |
|
 D. A. Pascual, J. M. Arribas, P. L. Tornel, F. Marin, C. Oliver, M. Ahumada, J. Gomez-Plana, P. Martinez, R. Arcas, and M. Valdes Preoperative Statin Therapy and Troponin T Predict Early Complications of Coronary Artery Surgery Ann. Thorac. Surg., January 1, 2006; 81(1): 78 - 83. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Hindler, C. S. Cleeland, E. Rivera, and C. D. Collard The Role of Statins in Cancer Therapy. Oncologist, January 1, 2006; 11(3): 306 - 315. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Sun, T. Koike, T. Ichikawa, K. Hatakeyama, M. Shiomi, B. Zhang, S. Kitajima, M. Morimoto, T. Watanabe, Y. Asada, et al. C-Reactive Protein in Atherosclerotic Lesions: Its Origin and Pathophysiological Significance Am. J. Pathol., October 1, 2005; 167(4): 1139 - 1148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. F. Bonvini, T. Hendiri, and E. Camenzind Inflammatory response post-myocardial infarction and reperfusion: a new therapeutic target? Eur. Heart J. Suppl., October 1, 2005; 7(suppl_I): I27 - I36. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Erkkila, M. Jauhiainen, K. Laitinen, K. Haasio, T. Tiirola, P. Saikku, and M. Leinonen Effect of Simvastatin, an Established Lipid-Lowering Drug, on Pulmonary Chlamydia pneumoniae Infection in Mice Antimicrob. Agents Chemother., September 1, 2005; 49(9): 3959 - 3962. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-J. Li and C.-H. Fang Effects of 4 Weeks of Atorvastatin Administration on the Antiinflammatory Cytokine Interleukin-10 in Patients with Unstable Angina Clin. Chem., September 1, 2005; 51(9): 1735 - 1738. [Full Text] [PDF]
|
|
|
|
|
|
R. A.H. Stewart, H. D. White, A. C. Kirby, S. R. Heritier, R. J. Simes, P. J. Nestel, M. J. West, D. M. Colquhoun, A. M. Tonkin, and for the Long-Term Intervention With Pravastatin in White Blood Cell Count Predicts Reduction in Coronary Heart Disease Mortality With Pravastatin Circulation, April 12, 2005; 111(14): 1756 - 1762. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Yonemura, Y. Momiyama, Z. A. Fayad, M. Ayaori, R. Ohmori, K. Higashi, T. Kihara, S. Sawada, N. Iwamoto, M. Ogura, et al. Effect of lipid-lowering therapy with atorvastatin on atherosclerotic aortic plaques detected by noninvasive magnetic resonance imaging J. Am. Coll. Cardiol., March 1, 2005; 45(5): 733 - 742. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Nissen, E. M. Tuzcu, P. Schoenhagen, T. Crowe, W. J. Sasiela, J. Tsai, J. Orazem, R. D. Magorien, C. O'Shaughnessy, P. Ganz, et al. Statin Therapy, LDL Cholesterol, C-Reactive Protein, and Coronary Artery Disease N. Engl. J. Med., January 6, 2005; 352(1): 29 - 38. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. A. Spencer, G. C. Fonarow, P. D. Frederick, R. S. Wright, N. Every, R. J. Goldberg, J. M. Gore, W. Dong, R. C. Becker, W. French, et al. Early Withdrawal of Statin Therapy in Patients With Non-ST-Segment Elevation Myocardial Infarction: National Registry of Myocardial Infarction Arch Intern Med, October 25, 2004; 164(19): 2162 - 2168. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-S. Lee, C.-C. Chang, Y. Zhu, and J. Y.-J. Shyy Simvastatin Induces Heme Oxygenase-1: A Novel Mechanism of Vessel Protection Circulation, September 7, 2004; 110(10): 1296 - 1302. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Fliser, K. Buchholz, H. Haller, and for the EUropean Trial on Olmesartan and Pravastat Antiinflammatory Effects of Angiotensin II Subtype 1 Receptor Blockade in Hypertensive Patients With Microinflammation Circulation, August 31, 2004; 110(9): 1103 - 1107. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Kluft Identifying patients at risk of coronary vascular disease: the potential role of inflammatory markers Eur. Heart J. Suppl., July 1, 2004; 6(suppl_C): C21 - C27. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Paoletti, A. M. Gotto Jr, and D. P. Hajjar Inflammation in Atherosclerosis and Implications for Therapy Circulation, June 15, 2004; 109(23_suppl_1): III-20 - III-26. [Abstract] [Full Text]
|
|
|
|
|
|
J. Davignon Beneficial Cardiovascular Pleiotropic Effects of Statins Circulation, June 15, 2004; 109(23_suppl_1): III-39 - III-43. [Abstract] [Full Text]
|
|
|
|
|
|
M. Schillinger, M. Exner, W. Mlekusch, J. Amighi, S. Sabeti, M. Muellner, H. Rumpold, O. Wagner, and E. Minar Statin therapy improves cardiovascular outcome of patients with peripheral artery disease Eur. Heart J., May 1, 2004; 25(9): 742 - 748. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Verma, P. E. Szmitko, and E. T.H. Yeh C-Reactive Protein: Structure Affects Function Circulation, April 27, 2004; 109(16): 1914 - 1917. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Nomura, A. Shouzu, S. Omoto, M. Nishikawa, and T. Iwasaka Effects of Losartan and Simvastatin on Monocyte-Derived Microparticles in Hypertensive Patients With and Without Type 2 Diabetes Mellitus Clinical and Applied Thrombosis/Hemostasis, April 1, 2004; 10(2): 133 - 141. [Abstract] [PDF]
|
|
|
|
 |
|
 B. L. Stauffer, G. L. Hoetzer, D. T. Smith, and C. A. DeSouza Plasma C-reactive protein is not elevated in physically active postmenopausal women taking hormone replacement therapy J Appl Physiol, January 1, 2004; 96(1): 143 - 148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.M. Hirschfield and M.B. Pepys C-reactive protein and cardiovascular disease: new insights from an old molecule QJM, November 1, 2003; 96(11): 793 - 807. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Marcovina, M. L. Koschinsky, J. J. Albers, and S. Skarlatos Report of the National Heart, Lung, and Blood Institute Workshop on Lipoprotein(a) and Cardiovascular Disease: Recent Advances and Future Directions Clin. Chem., November 1, 2003; 49(11): 1785 - 1796. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M Cummings, D. E King, and A. G Mainous III C-Reactive Protein, Antiinflammatory Drugs, and Quality of Life in Diabetes Ann. Pharmacother., November 1, 2003; 37(11): 1593 - 1597. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Balk, J. Lau, L. C. Goudas, H. S. Jordan, B. Kupelnick, L. U. Kim, and R. H. Karas Effects of Statins on Nonlipid Serum Markers Associated with Cardiovascular Disease: A Systematic Review Ann Intern Med, October 21, 2003; 139(8): 670 - 682. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Kereiakes Adjunctive Pharmacotherapy before Percutaneous Coronary Intervention in Non-ST-Elevation Acute Coronary Syndromes: The Role of Modulating Inflammation Circulation, October 21, 2003; 108(90161): III-22 - 27. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. M. Shamsuzzaman, B. J. Gersh, and V. K. Somers Obstructive Sleep Apnea: Implications for Cardiac and Vascular Disease JAMA, October 8, 2003; 290(14): 1906 - 1914. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Liu, S.-P. Zhao, Y.-C. Cheng, and Y.-L. Li Xuezhikang Decreases Serum Lipoprotein(a) and C-reactive Protein Concentrations in Patients with Coronary Heart Disease Clin. Chem., August 1, 2003; 49(8): 1347 - 1352. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kobayashi, N. Inoue, Y. Ohashi, M. Terashima, K. Matsui, T. Mori, H. Fujita, K. Awano, K. Kobayashi, H. Azumi, et al. Interaction of Oxidative Stress and Inflammatory Response in Coronary Plaque Instability: Important Role of C-Reactive Protein Arterioscler. Thromb. Vasc. Biol., August 1, 2003; 23(8): 1398 - 1404. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. W. Chan, D. L. Bhatt, D. P. Chew, J. Reginelli, J. P. Schneider, E. J. Topol, and S. G. Ellis Relation of Inflammation and Benefit of Statins After Percutaneous Coronary Interventions Circulation, April 8, 2003; 107(13): 1750 - 1756. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. T.H. Yeh and J. T. Willerson Coming of Age of C-Reactive Protein: Using Inflammation Markers in Cardiology Circulation, January 28, 2003; 107(3): 370 - 371. [Full Text] [PDF]
|
|