on September 2, 2003
Circulation. 2003
Published online before print September 2, 2003, doi: 10.1161/01.CIR.0000090690.67322.51
Published online before print September 2, 2003, doi: 10.1161/01.CIR.0000090690.67322.51
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Submitted on March 28, 2003
From the University of Hamburg, Department of Cardiology, Hamburg, Germany (S.B., T. Münzel, T. Meinertz); Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Frankfurt, Germany (C.H., A.M.Z.); University of California at Davis, Department of Internal Medicine and Department of Human Physiology, Davis, Calif (J.P.E.); Erasmus University, Thoraxcentre, Rotterdam, Netherlands (M.L.S.); and Kerckhoff Heart Center, Bad Nauheim, Germany (C.W.H.).\
*These authors contributed equally to this work. * To whom correspondence should be addressed. E-mail: baldus{at}uke.uni-hamburg.de.
Background--Polymorphonuclear neutrophils (PMNs) have gained attention as critical mediators of acute coronary syndromes (ACS). Myeloperoxidase (MPO), a hemoprotein abundantly expressed by PMNs and secreted during activation, possesses potent proinflammatory properties and may contribute directly to tissue injury. However, whether MPO also provides prognostic information in patients with ACS remains unknown. Methods and Results--MPO serum levels were assessed in 1090 patients with ACS. We recorded death and myocardial infarctions during 6 months of follow-up. MPO levels did not correlate with troponin T, soluble CD40 ligand, or C-reactive protein levels or with ST-segment changes. However, patients with elevated MPO levels (>350 µg/L; 31.3%) experienced a markedly increased cardiac risk (adjusted hazard ratio [HR] 2.25 [1.32 to 3.82]; P=0.003). In particular, MPO serum levels identified patients at risk who had troponin T levels below 0.01 µg/L (adjusted HR 7.48 [95% CI 1.98 to 28.29]; P=0.001). In a multivariate model that included other biochemical markers, troponin T (HR 1.99; P=0.023), C-reactive protein (1.25; P=0.044), vascular endothelial growth factor (HR 1.87; P=0.041), soluble CD40 ligand (HR 2.78; P<0.001), and MPO (HR 2.11; P=0.008) were all independent predictors of the patient's 6-month outcome. Conclusions--In patients with ACS, MPO serum levels powerfully predict an increased risk for subsequent cardiovascular events and extend the prognostic information gained from traditional biochemical markers. Given its proinflammatory properties, MPO may serve as both a marker and mediator of vascular inflammation and further points toward the significance of PMN activation in the pathophysiology of ACS.
Revised on July 9, 2003
Accepted on July 10, 2003
Myeloperoxidase Serum Levels Predict Risk in Patients With Acute Coronary Syndromes
Stephan Baldus MD*,
Key words: angina • myocardial infarction • leukocytes • prognosis • inflammation
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 D. Lau, H. Mollnau, J. P. Eiserich, B. A. Freeman, A. Daiber, U. M. Gehling, J. Brummer, V. Rudolph, T. Munzel, T. Heitzer, et al. Myeloperoxidase mediates neutrophil activation by association with CD11b/CD18 integrins PNAS, January 11, 2005; 102(2): 431 - 436. [Abstract] [Full Text] [PDF]
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L. Zheng, M. Settle, G. Brubaker, D. Schmitt, S. L. Hazen, J. D. Smith, and M. Kinter Localization of Nitration and Chlorination Sites on Apolipoprotein A-I Catalyzed by Myeloperoxidase in Human Atheroma and Associated Oxidative Impairment in ABCA1-dependent Cholesterol Efflux from Macrophages J. Biol. Chem., January 7, 2005; 280(1): 38 - 47. [Abstract] [Full Text] [PDF]
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L. M. Biasucci CDC/AHA Workshop on Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: Clinical Use of Inflammatory Markers in Patients With Cardiovascular Diseases: A Background Paper Circulation, December 21, 2004; 110(25): e560 - e567. [Abstract] [Full Text] [PDF]
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 C. Zhang, J. Yang, and L. K. Jennings Leukocyte-Derived Myeloperoxidase Amplifies High-Glucose--Induced Endothelial Dysfunction Through Interaction With High-Glucose--Stimulated, Vascular Non--Leukocyte-Derived Reactive Oxygen Species Diabetes, November 1, 2004; 53(11): 2950 - 2959. [Abstract] [Full Text] [PDF]
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T. Khreiss, L. Jozsef, L. A. Potempa, and J. G. Filep Opposing Effects of C-Reactive Protein Isoforms on Shear-Induced Neutrophil-Platelet Adhesion and Neutrophil Aggregation in Whole Blood Circulation, October 26, 2004; 110(17): 2713 - 2720. [Abstract] [Full Text] [PDF]
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P. J. Mateos-Caceres, A. Garcia-Mendez, A. Lopez Farre, C. Macaya, A. Nunez, J. Gomez, S. Alonso-Orgaz, C. Carrasco, M. E. Burgos, R. de Andres, et al. Proteomic analysis of plasma from patients during an acute coronary syndrome J. Am. Coll. Cardiol., October 19, 2004; 44(8): 1578 - 1583. [Abstract] [Full Text] [PDF]
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A. P. Miller, W. Feng, D. Xing, N. M. Weathington, J. E. Blalock, Y.-F. Chen, and S. Oparil Estrogen Modulates Inflammatory Mediator Expression and Neutrophil Chemotaxis in Injured Arteries Circulation, September 21, 2004; 110(12): 1664 - 1669. [Abstract] [Full Text] [PDF]
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J. A. Vita, M.-L. Brennan, N. Gokce, S. A. Mann, M. Goormastic, M. H. Shishehbor, M. S. Penn, J. F. Keaney Jr, and S. L. Hazen Serum Myeloperoxidase Levels Independently Predict Endothelial Dysfunction in Humans Circulation, August 31, 2004; 110(9): 1134 - 1139. [Abstract] [Full Text] [PDF]
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A. S. Jaffe and H. Katus Acute Coronary Syndrome Biomarkers: The Need for More Adequate Reporting Circulation, July 13, 2004; 110(2): 104 - 106. [Full Text] [PDF]
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M. Panteghini Role and importance of biochemical markers in clinical cardiology Eur. Heart J., July 2, 2004; 25(14): 1187 - 1196. [Abstract] [Full Text] [PDF]
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S. L. Hazen Myeloperoxidase and Plaque Vulnerability Arterioscler Thromb Vasc Biol, July 1, 2004; 24(7): 1143 - 1146. [Full Text] [PDF]
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 M. Kemp, J. Donovan, H. Higham, and J. Hooper Biochemical markers of myocardial injury Br. J. Anaesth., July 1, 2004; 93(1): 63 - 73. [Abstract] [Full Text] [PDF]
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S. Sugiyama, K. Kugiyama, M. Aikawa, S. Nakamura, H. Ogawa, and P. Libby Hypochlorous Acid, a Macrophage Product, Induces Endothelial Apoptosis and Tissue Factor Expression: Involvement of Myeloperoxidase-Mediated Oxidant in Plaque Erosion and Thrombogenesis Arterioscler Thromb Vasc Biol, July 1, 2004; 24(7): 1309 - 1314. [Abstract] [Full Text] [PDF]
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P. M Ridker, N. J. Brown, D. E. Vaughan, D. G. Harrison, and J. L. Mehta Established and Emerging Plasma Biomarkers in the Prediction of First Atherothrombotic Events Circulation, June 29, 2004; 109(25_suppl_1): IV-6 - IV-19. [Full Text] [PDF]
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C. Tiruppathi, T. Naqvi, Y. Wu, S. M. Vogel, R. D. Minshall, and A. B. Malik Albumin mediates the transcytosis of myeloperoxidase by means of caveolae in endothelial cells PNAS, May 18, 2004; 101(20): 7699 - 7704. [Abstract] [Full Text] [PDF]
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C. Wang, C. Jiao, H. D. Hanlon, W. Zheng, R. J. Tomanek, and G. C. Schatteman Mechanical, cellular, and molecular factors interact to modulate circulating endothelial cell progenitors Am J Physiol Heart Circ Physiol, May 1, 2004; 286(5): H1985 - H1993. [Abstract] [Full Text] [PDF]
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A. P. Kumar, F. J. Piedrafita, and W. F. Reynolds Peroxisome Proliferator-activated Receptor {gamma} Ligands Regulate Myeloperoxidase Expression in Macrophages by an Estrogen-dependent Mechanism Involving the -463GA Promoter Polymorphism J. Biol. Chem., February 27, 2004; 279(9): 8300 - 8315. [Abstract] [Full Text] [PDF]
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A. Elsaesser and C. W. Hamm Acute Coronary Syndrome: The Risk of Being Female Circulation, February 10, 2004; 109(5): 565 - 567. [Full Text] [PDF]
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 W. E. Cayley Jr., F. W. Asselbergs, J.-W. Cohen Tervaert, R. A. Tio, M.-L. Brennan, M. S. Penn, and S. L. Hazen Prognostic Value of Myeloperoxidase in Patients with Chest Pain N. Engl. J. Med., January 29, 2004; 350(5): 516 - 518. [Full Text] [PDF]
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