(Circulation. 2000;101:2149.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Elevation of Tumor Necrosis Factor-
and Increased Risk of Recurrent Coronary Events After Myocardial Infarction
From the Leducq Center for Molecular and Genetic Epidemiology of Cardiovascular Disorders (P.M.R.), the Center for Cardiovascular Prevention (P.M.R.), Division of Cardiovascular Diseases (P.M.R., M.P., F.S., E.B.) and the Division of Preventive Medicine (P.M.R.), Brigham and Women’s Hospital; the Department of Pathology, Children’s Hospital Medical Center (N.R.), Harvard Medical School, Boston, Mass; and the Centre Universitaire de Sante de l’Estrie (S.L.), Sherbrooke, Quebec, Canada.
Correspondence to Dr Paul M. Ridker, Cardiovascular Diseases, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115.
Background—Levels of tumor
necrosis factor-
(TNF-) increase with acute ischemia.
However, whether elevations of TNF- in the stable phase after
myocardial ischemia (MI) are associated with increased risk of
recurrent coronary events is unknown.
Methods and Results—A nested case-control design was used to
compare TNF- levels obtained an average of 8.9 months after initial
MI among 272 participants in the Cholesterol And Recurrent
Events (CARE) trial who subsequently developed recurrent nonfatal MI or
a fatal cardiovascular event (cases) and from an equal
number of age- and sex-matched participants who remained free of these
events during follow-up (controls). Overall, TNF- levels were
significantly higher among cases than controls (2.84 versus 2.57 pg/mL,
P=0.02). The excess risk of recurrent coronary
events after MI was predominantly seen among those with the highest
levels of TNF-, such that those with levels in excess of 4.17 pg/mL
(the 95th percentile of the control distribution) had an 
3-fold
increase in risk (RR=2.7, 95% CI 1.4 to 5.2, P=0.004).
Risk estimates were independent of other risk factors and were similar
in subgroup analyses limited to cardiovascular
death (RR=2.1) or to recurrent nonfatal MI (RR=3.2).
Conclusions—Plasma concentrations of TNF- are persistently
elevated among post-MI patients at increased risk for recurrent
coronary events. These data support the hypothesis that a
persistent inflammatory instability is present among stable
patients at increased vascular risk. Novel therapies designed to
attenuate inflammation may thus represent a new direction in
the treatment of MI.
Key Words: inflammation • myocardial infarction • tumor necrosis factor • atherosclerosis
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L S Rallidis, M G Zolindaki, P C Pentzeridis, K P Poulopoulos, A H Velissaridou, and T S Apostolou Raised concentrations of macrophage colony stimulating factor in severe unstable angina beyond the acute phase are strongly predictive of long term outcome Heart, January 1, 2004; 90(1): 25 - 29. [Abstract] [Full Text] [PDF]
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E. Lutgens, R.-J. van Suylen, B. C. Faber, M. J. Gijbels, P. M. Eurlings, A.-P. Bijnens, K. B. Cleutjens, S. Heeneman, and M. J.A.P. Daemen Atherosclerotic Plaque Rupture: Local or Systemic Process? Arterioscler Thromb Vasc Biol, December 1, 2003; 23(12): 2123 - 2130. [Abstract] [Full Text] [PDF]
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T. Mazurek, L. Zhang, A. Zalewski, J. D. Mannion, J. T. Diehl, H. Arafat, L. Sarov-Blat, S. O'Brien, E. A. Keiper, A. G. Johnson, et al. Human Epicardial Adipose Tissue Is a Source of Inflammatory Mediators Circulation, November 18, 2003; 108(20): 2460 - 2466. [Abstract] [Full Text] [PDF]
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P. Schoenhagen, G. W. Stone, S. E. Nissen, C. L. Grines, J. Griffin, B. S. Clemson, D. G. Vince, K. Ziada, T. Crowe, C. Apperson-Hanson, et al. Coronary Plaque Morphology and Frequency of Ulceration Distant From Culprit Lesions in Patients With Unstable and Stable Presentation Arterioscler Thromb Vasc Biol, October 1, 2003; 23(10): 1895 - 1900. [Abstract] [Full Text] [PDF]
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A. P. Miller, Y.-F. Chen, D. Xing, W. Feng, and S. Oparil Hormone Replacement Therapy and Inflammation: Interactions in Cardiovascular Disease Hypertension, October 1, 2003; 42(4): 657 - 663. [Abstract] [Full Text] [PDF]
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 L. J. Dacey, J. DeSimone, J. H. Braxton, B. J. Leavitt, S. J. Lahey, J. D. Klemperer, B. M. Westbrook, E. M. Olmstead, and G. T. O'Connor Preoperative white blood cell count and mortality and morbidity after coronary artery bypass grafting Ann. Thorac. Surg., September 1, 2003; 76(3): 760 - 764. [Abstract] [Full Text] [PDF]
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T. Pischon, S. E. Hankinson, G. S. Hotamisligil, N. Rifai, W. C. Willett, and E. B. Rimm Habitual Dietary Intake of n-3 and n-6 Fatty Acids in Relation to Inflammatory Markers Among US Men and Women Circulation, July 15, 2003; 108(2): 155 - 160. [Abstract] [Full Text] [PDF]
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 H. F. Berg, B. Maraha, G.-J. Scheffer, M. F. Peeters, and J. A. J. W. Kluytmans Effect of Clarithromycin on Inflammatory Markers in Patients with Atherosclerosis Clin. Vaccine Immunol., July 1, 2003; 10(4): 525 - 528. [Abstract] [Full Text] [PDF]
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E. C. Suarez, R. R. Krishnan, and J. G. Lewis The Relation of Severity of Depressive Symptoms to Monocyte-Associated Proinflammatory Cytokines and Chemokines in Apparently Healthy Men Psychosom Med, May 1, 2003; 65(3): 362 - 368. [Abstract] [Full Text] [PDF]
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J.-P. Despres, I. Lemieux, A. Pascot, N. Almeras, M. Dumont, A. Nadeau, J. Bergeron, and D. Prud'homme Gemfibrozil Reduces Plasma C-Reactive Protein Levels in Abdominally Obese Men With the Atherogenic Dyslipidemia of the Metabolic Syndrome Arterioscler Thromb Vasc Biol, April 1, 2003; 23(4): 702 - 703. [Full Text] [PDF]
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S. Chia, M. Qadan, R. Newton, C. A. Ludlam, K. A.A. Fox, and D. E. Newby Intra-Arterial Tumor Necrosis Factor-{alpha} Impairs Endothelium-Dependent Vasodilatation and Stimulates Local Tissue Plasminogen Activator Release in Humans Arterioscler Thromb Vasc Biol, April 1, 2003; 23(4): 695 - 701. [Abstract] [Full Text] [PDF]
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S. Blankenberg, H. J. Rupprecht, O. Poirier, C. Bickel, M. Smieja, G. Hafner, J. Meyer, F. Cambien, L. Tiret, and for the AtheroGene Investigators Plasma Concentrations and Genetic Variation of Matrix Metalloproteinase 9 and Prognosis of Patients With Cardiovascular Disease Circulation, April 1, 2003; 107(12): 1579 - 1585. [Abstract] [Full Text] [PDF]
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D. R. Murray and G. L. Freeman Proinflammatory Cytokines: Predictors of a Failing Heart? Circulation, March 25, 2003; 107(11): 1460 - 1462. [Full Text] [PDF]
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R. S. Vasan, L. M. Sullivan, R. Roubenoff, C. A. Dinarello, T. Harris, E. J. Benjamin, D. B. Sawyer, D. Levy, P. W.F. Wilson, and R. B. D'Agostino Inflammatory Markers and Risk of Heart Failure in Elderly Subjects Without Prior Myocardial Infarction: The Framingham Heart Study Circulation, March 25, 2003; 107(11): 1486 - 1491. [Abstract] [Full Text] [PDF]
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 J. H. Von der Thusen, J. Kuiper, T. J. C. Van Berkel, and E. A. L. Biessen Interleukins in Atherosclerosis: Molecular Pathways and Therapeutic Potential Pharmacol. Rev., March 1, 2003; 55(1): 133 - 166. [Abstract] [Full Text] [PDF]
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S. Chia, C. A. Ludlam, K. A. A. Fox, and D. E. Newby Acute systemic inflammation enhances endothelium-dependent tissue plasminogen activator release in men J. Am. Coll. Cardiol., January 15, 2003; 41(2): 333 - 339. [Abstract] [Full Text] [PDF]
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K. Esposito, F. Nappo, R. Marfella, G. Giugliano, F. Giugliano, M. Ciotola, L. Quagliaro, A. Ceriello, and D. Giugliano Inflammatory Cytokine Concentrations Are Acutely Increased by Hyperglycemia in Humans: Role of Oxidative Stress Circulation, October 15, 2002; 106(16): 2067 - 2072. [Abstract] [Full Text] [PDF]
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D. Tanne, M. Haim, V. Boyko, U. Goldbourt, T. Reshef, S. Matetzky, Y. Adler, Y. A. Mekori, and S. Behar Soluble Intercellular Adhesion Molecule-1 and Risk of Future Ischemic Stroke: A Nested Case-Control Study From the Bezafibrate Infarction Prevention (BIP) Study Cohort Stroke, September 1, 2002; 33(9): 2182 - 2186. [Abstract] [Full Text] [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. K. Koh Effects of estrogen on the vascular wall: vasomotor function and inflammation Cardiovasc Res, September 1, 2002; 55(4): 714 - 726. [Full Text] [PDF]
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P. Schoenhagen, E. M. Tuzcu, and S. G. Ellis Plaque Vulnerability, Plaque Rupture, and Acute Coronary Syndromes: (Multi)-Focal Manifestation of a Systemic Disease Process Circulation, August 13, 2002; 106(7): 760 - 762. [Full Text] [PDF]
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K. Esposito, A. Pontillo, M. Ciotola, C. Di Palo, E. Grella, G. Nicoletti, and D. Giugliano Weight Loss Reduces Interleukin-18 Levels in Obese Women J. Clin. Endocrinol. Metab., August 1, 2002; 87(8): 3864 - 3866. [Abstract] [Full Text] [PDF]
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S. Kiechl, E. Lorenz, M. Reindl, C. J. Wiedermann, F. Oberhollenzer, E. Bonora, J. Willeit, and D. A. Schwartz Toll-like Receptor 4 Polymorphisms and Atherogenesis N. Engl. J. Med., July 18, 2002; 347(3): 185 - 192. [Abstract] [Full Text] [PDF]
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P. Libby, P. M. Ridker, and A. Maseri Inflammation and Atherosclerosis Circulation, March 5, 2002; 105(9): 1135 - 1143. [Abstract] [Full Text] [PDF]
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G.J. Blake and P.M. Ridker Tumour necrosis factor-{alpha}, inflammatory biomarkers, and atherogenesis Eur. Heart J., March 1, 2002; 23(5): 345 - 347. [Full Text] [PDF]
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T. Skoog, W. Dichtl, S. Boquist, C. Skoglund-Andersson, F. Karpe, R. Tang, M.G. Bond, U. de Faire, J. Nilsson, P. Eriksson, et al. Plasma tumour necrosis factor-{alpha} and early carotid atherosclerosis in healthy middle-aged men Eur. Heart J., March 1, 2002; 23(5): 376 - 383. [Abstract] [Full Text] [PDF]
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M. S. Elkind, J. Cheng, B. Boden-Albala, T. Rundek, J. Thomas, H. Chen, L. E. Rabbani, R. L. Sacco, and A. G. Thrift Tumor Necrosis Factor Receptor Levels Are Associated With Carotid Atherosclerosis * Editorial Comment Stroke, January 1, 2002; 33(1): 31 - 38. [Abstract] [Full Text] [PDF]
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