(Circulation. 2000;102:1000.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Elevated C-Reactive Protein Levels and Impaired Endothelial Vasoreactivity in Patients With Coronary Artery Disease
From the Department of Internal Medicine IV, Division of Cardiology, Johann W. Goethe University, Frankfurt, Germany.
Correspondence to Andreas M. Zeiher, MD, Department of Internal Medicine IV, Division of Cardiology, Johann W. Goethe University, Theodor Stern Kai 7, D-60590 Frankfurt, Germany. E-mail zeiher{at}em.uni-frankfurt.de
Background—Elevated C-reactive protein (CRP) serum levels, an exquisitely sensitive objective marker of inflammation, relate to long-term prognosis in patients with coronary artery disease and in apparently healthy men. Because abnormalities of endothelial regulation of vascular function may contribute to the occurrence of coronary events, we tested the hypothesis that elevated CRP levels are associated with an abnormal systemic endothelial vascular reactivity.
Methods and Results—Endothelium-dependent (10 to 50 µg/min acetylcholine) and endothelium-independent (2 to 8 µg/min sodium nitroprusside) forearm blood flow responses were measured with venous occlusion plethysmography in 60 male patients with angiographically documented coronary artery disease. Forearm blood flow responses to acetylcholine were inversely correlated with CRP serum levels (r=-0.46, P=0.001). With multivariate analysis that included the classic risk factors for coronary artery disease, elevated CRP serum level remained a statistically significant independent predictor of a blunted endothelial vasodilator capacity. Most important, normalization of elevated CRP levels over time was associated with a normalization of endothelium-mediated forearm blood flow responses after 3 months.
Conclusions—Thus, elevated CRP serum levels indicative of a systemic inflammatory response are associated with a blunted systemic endothelial vasodilator function. The identification of elevated CRP levels as a transient independent risk factor for endothelial dysfunction might provide an important clue to link a systemic marker of inflammation to atherosclerotic disease progression.
Key Words: endothelium • proteins • blood flow • coronary disease • angina • inflammation
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D.J. Brull, N. Serrano, F. Zito, L. Jones, H.E. Montgomery, A. Rumley, P. Sharma, G.D.O. Lowe, M.J. World, S.E. Humphries, et al. Human CRP Gene Polymorphism Influences CRP Levels: Implications for the Prediction and Pathogenesis of Coronary Heart Disease Arterioscler Thromb Vasc Biol, November 1, 2003; 23(11): 2063 - 2069. [Abstract] [Full Text] [PDF]
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S. Verma, M. R. Buchanan, and T. J. Anderson Endothelial Function Testing as a Biomarker of Vascular Disease Circulation, October 28, 2003; 108(17): 2054 - 2059. [Full Text] [PDF]
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S. K. Venugopal, S. Devaraj, and I. Jialal C-Reactive Protein Decreases Prostacyclin Release From Human Aortic Endothelial Cells Circulation, October 7, 2003; 108(14): 1676 - 1678. [Abstract] [Full Text] [PDF]
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M. E. Widlansky, N. Gokce, J. F. Keaney Jr, and J. A. Vita The clinical implications of endothelial dysfunction J. Am. Coll. Cardiol., October 1, 2003; 42(7): 1149 - 1160. [Abstract] [Full Text] [PDF]
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A. Hognestad, K. Endresen, R. Wergeland, O. Stokke, O. Geiran, T. Holm, S. Simonsen, J. K. Kjekshus, and A. K. Andreassen Plasma C-reactive protein as a marker of cardiac allograft vasculopathy in heart transplant recipients J. Am. Coll. Cardiol., August 6, 2003; 42(3): 477 - 482. [Abstract] [Full Text] [PDF]
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S. Taddei, N. Caraccio, A. Virdis, A. Dardano, D. Versari, L. Ghiadoni, A. Salvetti, E. Ferrannini, and F. Monzani Impaired Endothelium-Dependent Vasodilatation in Subclinical Hypothyroidism: Beneficial Effect of Levothyroxine Therapy J. Clin. Endocrinol. Metab., August 1, 2003; 88(8): 3731 - 3737. [Abstract] [Full Text] [PDF]
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S. Amar, N. Gokce, S. Morgan, M. Loukideli, T. E. Van Dyke, and J. A. Vita Periodontal Disease Is Associated With Brachial Artery Endothelial Dysfunction and Systemic Inflammation Arterioscler Thromb Vasc Biol, July 1, 2003; 23(7): 1245 - 1249. [Abstract] [Full Text] [PDF]
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J. T. Kuvin and R. H. Karas Clinical Utility of Endothelial Function Testing: Ready for Prime Time? Circulation, July 1, 2003; 107(25): 3243 - 3247. [Full Text] [PDF]
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R. A. Vogel Heads and Hearts: The Endothelial Connection Circulation, June 10, 2003; 107(22): 2766 - 2768. [Full Text] [PDF]
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J. Cosin-Sales, C. Pizzi, S. Brown, and J. C. Kaski C-reactive protein, clinical presentation, and ischemic activity in patients with chest pain and normal coronary angiograms J. Am. Coll. Cardiol., May 7, 2003; 41(9): 1468 - 1474. [Abstract] [Full Text] [PDF]
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D. E. King, A. G. Mainous III, T. A. Buchanan, and W. S. Pearson C-Reactive Protein and Glycemic Control in Adults With Diabetes Diabetes Care, May 1, 2003; 26(5): 1535 - 1539. [Abstract] [Full Text] [PDF]
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P. Khairy, S. Rinfret, J.-C. Tardif, R. Marchand, S. Shapiro, J. Brophy, and J. Dupuis Absence of Association Between Infectious Agents and Endothelial Function in Healthy Young Men Circulation, April 22, 2003; 107(15): 1966 - 1971. [Abstract] [Full Text] [PDF]
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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]
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T. H. Schindler, B. Hornig, P. T. Buser, M. Olschewski, N. Magosaki, M. Pfisterer, E. U. Nitzsche, U. Solzbach, and H. Just Prognostic Value of Abnormal Vasoreactivity of Epicardial Coronary Arteries to Sympathetic Stimulation in Patients With Normal Coronary Angiograms Arterioscler Thromb Vasc Biol, March 1, 2003; 23(3): 495 - 501. [Abstract] [Full Text] [PDF]
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 C. R. Isasi, R. J. Deckelbaum, R. P. Tracy, T. J. Starc, L. Berglund, and S. Shea Physical Fitness and C-Reactive Protein Level in Children and Young Adults: The Columbia University BioMarkers Study Pediatrics, February 1, 2003; 111(2): 332 - 338. [Abstract] [Full Text] [PDF]
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R. Chenevard, D. Hurlimann, M. Bechir, F. Enseleit, L. Spieker, M. Hermann, W. Riesen, S. Gay, R. E. Gay, M. Neidhart, et al. Selective COX-2 Inhibition Improves Endothelial Function in Coronary Artery Disease Circulation, January 28, 2003; 107(3): 405 - 409. [Abstract] [Full Text] [PDF]
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The ENCORE Investigators* Effect of Nifedipine and Cerivastatin on Coronary Endothelial Function in Patients With Coronary Artery Disease: The ENCORE I Study (Evaluation of Nifedipine and Cerivastatin On Recovery of coronary Endothelial function) Circulation, January 28, 2003; 107(3): 422 - 428. [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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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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S. K. Venugopal, S. Devaraj, I. Yuhanna, P. Shaul, and I. Jialal Demonstration That C-Reactive Protein Decreases eNOS Expression and Bioactivity in Human Aortic Endothelial Cells Circulation, September 17, 2002; 106(12): 1439 - 1441. [Abstract] [Full Text] [PDF]
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A. Decensi, U. Omodei, C. Robertson, B. Bonanni, A. Guerrieri-Gonzaga, F. Ramazzotto, H. Johansson, S. Mora, M. T. Sandri, M. Cazzaniga, et al. Effect of Transdermal Estradiol and Oral Conjugated Estrogen on C-Reactive Protein in Retinoid-Placebo Trial in Healthy Women Circulation, September 3, 2002; 106(10): 1224 - 1228. [Abstract] [Full Text] [PDF]
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S. P Marso Review: The pathogenesis of type 2 diabetes and cardiovascular disease The British Journal of Diabetes & Vascular Disease, September 1, 2002; 2(5): 350 - 356. [Abstract] [PDF]
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K. K. Koh, J. Y. Ahn, D. K. Jin, B.-K. Yoon, H. S. Kim, D. S. Kim, M.-S. Shin, J. W. Son, I. S. Choi, and E. K. Shin Effects of Continuous Combined Hormone Replacement Therapy on Inflammation in Hypertensive and/or Overweight Postmenopausal Women Arterioscler Thromb Vasc Biol, September 1, 2002; 22(9): 1459 - 1464. [Abstract] [Full Text] [PDF]
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K. B. Vallbracht, P. L. Schwimmbeck, B. Seeberg, U. Kuhl, and H.-P. Schultheiss Endothelial dysfunction of peripheral arteries in patients with immunohistologically confirmed myocardial inflammation correlates with endothelial expression of human leukocyte antigens and adhesion molecules in myocardial biopsies J. Am. Coll. Cardiol., August 7, 2002; 40(3): 515 - 520. [Abstract] [Full Text] [PDF]
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