(Circulation. 1999;100:96-102.)
© 1999 American Heart Association, Inc.
Current Perspective |
C-Reactive Protein as a Cardiovascular Risk Factor
More Than an Epiphenomenon?
From the Departments of Cardiology (W.K.L., C.A.V.), Pathology (H.W.M.N.), and Internal Medicine (C.E.H.), Free University Hospital, Amsterdam; Cardiovascular Research Institute Maastricht (CARIM) (W.T.H.), University of Maastricht; the Department of Cardiology (F.W.A.V.), University Hospital Sint Radboud, Nijmegen; and CLB (G.-J.W., C.E.H.), Sanquin Blood Supply Foundation, Amsterdam, The Netherlands.
Correspondence to Wim K. Lagrand, Free University Hospital, Department of Cardiology, PO Box 7057, NL 1007 MB Amsterdam, The Netherlands. E-mail cardiol{at}azvu.nl
Background—Circulating levels of C-reactive protein (CRP) may constitute an independent risk factor for cardiovascular disease. How CRP as a risk factor is involved in cardiovascular disease is still unclear.
Methods and Results—By reviewing available studies, we discuss explanations for the associations between CRP and cardiovascular disease. CRP levels within the upper quartile/quintile of the normal range constitute an increased risk for cardiovascular events, both in apparently healthy persons and in persons with preexisting angina pectoris. High CRP responses after acute myocardial infarction indicate an unfavorable outcome, even after correction for other risk factors. This link between CRP and cardiovascular disease has been considered to reflect the response of the body to the inflammatory reactions in the atherosclerotic (coronary) vessels and adjacent myocardium. However, because CRP localizes in infarcted myocardium (with colocalization of activated complement), we hypothesize that CRP may directly interact with atherosclerotic vessels or ischemic myocardium by activation of the complement system, thereby promoting inflammation and thrombosis.
Conclusions—CRP constitutes an independent cardiovascular risk factor. Unraveling the molecular background of this association may provide new directions for prevention of cardiovascular events.
Key Words: cardiovascular diseases • myocardial infarction • inflammation • risk factors • physiology
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S. K. James, P. Armstrong, E. Barnathan, R. Califf, B. Lindahl, A. Siegbahn, M. L. Simoons, E. J. Topol, P. Venge, L. Wallentin, et al. Troponin and C-reactive protein have different relations to subsequent mortality and myocardial infarction after acute coronary syndrome: A GUSTO-IV substudy J. Am. Coll. Cardiol., March 19, 2003; 41(6): 916 - 924. [Abstract] [Full Text] [PDF]
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T. Vainas, T. Lubbers, F. R.M. Stassen, S. B. Herngreen, M. P. van Dieijen-Visser, C. A. Bruggeman, P. J.E.H.M. Kitslaar, and G. W. H. Schurink Serum C-Reactive Protein Level Is Associated With Abdominal Aortic Aneurysm Size and May Be Produced by Aneurysmal Tissue Circulation, March 4, 2003; 107(8): 1103 - 1105. [Abstract] [Full Text] [PDF]
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R. Corti, V. Fuster, and J. J. Badimon Pathogenetic concepts of acute coronary syndromes J. Am. Coll. Cardiol., February 19, 2003; 41(4_Suppl_S): 7S - 14S. [Abstract] [Full Text] [PDF]
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J Oldgren, L Wallentin, L Grip, R Linder, B.L Norgaard, and A Siegbahn Myocardial damage, inflammation and thrombin inhibition in unstable coronary artery disease Eur. Heart J., January 1, 2003; 24(1): 86 - 93. [Abstract] [Full Text] [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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G. Engstrom, L. Janzon, G. Berglund, P. Lind, L. Stavenow, B. Hedblad, and F. Lindgarde Blood Pressure Increase and Incidence of Hypertension in Relation to Inflammation-Sensitive Plasma Proteins Arterioscler Thromb Vasc Biol, December 1, 2002; 22(12): 2054 - 2058. [Abstract] [Full Text] [PDF]
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C. Kluft, R. Kleemann, and M.P.M. de Maat How best to counteract the enemies? By controlling inflammation in the coronary circulation Eur. Heart J. Suppl., November 1, 2002; 4(suppl_G): G53 - G65. [Abstract] [PDF]
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L. Sternik, S. Samee, H. V. Schaff, K. J. Zehr, L. O. Lerman, D. R. Holmes, J. Herrmann, and A. Lerman C-Reactive Protein Relaxes Human Vessels In Vitro Arterioscler Thromb Vasc Biol, November 1, 2002; 22(11): 1865 - 1868. [Abstract] [Full Text] [PDF]
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T.S. Church, C.E. Barlow, C.P. Earnest, J.B. Kampert, E.L. Priest, and S.N. Blair Associations Between Cardiorespiratory Fitness and C-Reactive Protein in Men Arterioscler Thromb Vasc Biol, November 1, 2002; 22(11): 1869 - 1876. [Abstract] [Full Text] [PDF]
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R. P. Tracy Inflammation in Cardiovascular Disease: Cart, Horse or Both-Revisited Arterioscler Thromb Vasc Biol, October 1, 2002; 22(10): 1514 - 1515. [Full Text] [PDF]
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K. Winbeck, H. Poppert, T. Etgen, B. Conrad, and D. Sander Prognostic Relevance of Early Serial C-Reactive Protein Measurements After First Ischemic Stroke Stroke, October 1, 2002; 33(10): 2459 - 2464. [Abstract] [Full Text] [PDF]
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C. H. Toh, J. Samis, C. Downey, J. Walker, L. Becker, N. Brufatto, L. Tejidor, G. Jones, W. Houdijk, A. Giles, et al. Biphasic transmittance waveform in the APTT coagulation assay is due to the formation of a Ca++-dependent complex of C-reactive protein with very-low-density lipoprotein and is a novel marker of impending disseminated intravascular coagulation Blood, September 18, 2002; 100(7): 2522 - 2529. [Abstract] [Full Text] [PDF]
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T. J. Wang, M. G. Larson, D. Levy, E. J. Benjamin, M. J. Kupka, W. J. Manning, M. E. Clouse, R. B. D'Agostino, P. W.F. Wilson, and C. J. O'Donnell C-Reactive Protein Is Associated With Subclinical Epicardial Coronary Calcification in Men and Women: The Framingham Heart Study Circulation, September 3, 2002; 106(10): 1189 - 1191. [Abstract] [Full Text] [PDF]
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J. Oh, R. Wunsch, M. Turzer, M. Bahner, P. Raggi, U. Querfeld, O. Mehls, and F. Schaefer Advanced Coronary and Carotid Arteriopathy in Young Adults With Childhood-Onset Chronic Renal Failure Circulation, July 2, 2002; 106(1): 100 - 105. [Abstract] [Full Text] [PDF]
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A. J.G. Hanley, K. Williams, M. P. Stern, and S. M. Haffner Homeostasis Model Assessment of Insulin Resistance in Relation to the Incidence of Cardiovascular Disease: The San Antonio Heart Study Diabetes Care, July 1, 2002; 25(7): 1177 - 1184. [Abstract] [Full Text] [PDF]
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R.J. de Winter, G.S. Heyde, K.T. Koch, J. Fischer, J.P. van Straalen, M. Bax, C.E. Schotborgh, K.J. Mulder, G.T. Sanders, J.J. Piek, et al. The prognostic value of pre-procedural plasma C-reactive protein in patients undergoing elective coronary angioplasty Eur. Heart J., June 2, 2002; 23(12): 960 - 966. [Abstract] [Full Text] [PDF]
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A. S.M. Shamsuzzaman, M. Winnicki, P. Lanfranchi, R. Wolk, T. Kara, V. Accurso, and V. K. Somers Elevated C-Reactive Protein in Patients With Obstructive Sleep Apnea Circulation, May 28, 2002; 105(21): 2462 - 2464. [Abstract] [Full Text] [PDF]
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C. D.A. Stehouwer, M.-A. Gall, J. W.R. Twisk, E. Knudsen, J. J. Emeis, and H.-H. Parving Increased Urinary Albumin Excretion, Endothelial Dysfunction, and Chronic Low-Grade Inflammation in Type 2 Diabetes: Progressive, Interrelated, and Independently Associated With Risk of Death Diabetes, April 1, 2002; 51(4): 1157 - 1165. [Abstract] [Full Text] [PDF]
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M. A Vickers, F. R Green, C. Terry, B. M Mayosi, C. Julier, M. Lathrop, P. J Ratcliffe, H. C Watkins, and B. Keavney Genotype at a promoter polymorphism of the interleukin-6 gene is associated with baseline levels of plasma C-reactive protein Cardiovasc Res, March 1, 2002; 53(4): 1029 - 1034. [Abstract] [Full Text] [PDF]
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A. Tchernof, A. Nolan, C. K. Sites, P. A. Ades, and E. T. Poehlman Weight Loss Reduces C-Reactive Protein Levels in Obese Postmenopausal Women Circulation, February 5, 2002; 105(5): 564 - 569. [Abstract] [Full Text] [PDF]
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R. Nijmeijer, W. K Lagrand, A. Baidoshvili, Y. T.P Lubbers, W. T. Hermens, C. J.L.M Meijer, C. A Visser, C.E. Hack, and H. W.M Niessen Secretory type II phospholipase A2 binds to ischemic myocardium during myocardial infarction in humans Cardiovasc Res, January 1, 2002; 53(1): 138 - 146. [Abstract] [Full Text] [PDF]
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E. Rizos and D. P Mikhailidis Are high density lipoprotein (HDL) and triglyceride levels relevant in stroke prevention? Cardiovasc Res, November 1, 2001; 52(2): 199 - 207. [Abstract] [Full Text] [PDF]
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A. Galante, A. Pietroiusti, M. Vellini, P. Piccolo, G. Possati, M. De Bonis, R. L. Grillo, C. Fontana, and C. Favalli C-reactive protein is increased in patients with degenerative aortic valvular stenosis J. Am. Coll. Cardiol., October 1, 2001; 38(4): 1078 - 1082. [Abstract] [Full Text] [PDF]
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