(Circulation. 1997;96:4095-4103.)
© 1997 American Heart Association, Inc.
Articles |
Roles of Infectious Agents in Atherosclerosis and Restenosis1
An Assessment of the Evidence and Need for Future Research
From Brigham and Women's Hospital, Harvard Medical School, Boston, Mass (P.L.), and the National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Md (D.E., S.S.).
Correspondence to Peter Libby, MD, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, 221 Longwood Ave, Boston, MA 02115. E-mail plibby@bustoff.bwh.harvard.edu
Key Words: endothelium • leukocytes • muscle, smooth • risk factors • viruses
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Introduction |
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The past few years have witnessed a resurgence of interest in the possibility that infectious processes may contribute to arterial diseases, including atherosclerosis and restenosis after arterial intervention. The recent recognition that Helicobacter pylori contributes to peptic ulcers illustrates how a disease previously believed to result primarily from excessive gastric acid production often involves a microbial pathogen. Although hypercholesterolemia clearly predisposes to development of coronary heart disease, many patients with arterial pathology have serum cholesterol levels within or below the average range. Coronary heart disease frequently affects individuals who lack other traditional risk factors as well. These findings suggest that heretofore unrecognized risk factors may also contribute to the pathogenesis of coronary heart disease.
At a recent Special Emphasis Panel convened by the National Heart, Lung, and Blood Institute, a number of experts reviewed the evidence for links between infectious processes and atherosclerosis and restenosis. This report will summarize and examine critically the evidence for involvement of infectious agents in arterial diseases based on the deliberations of this expert panel. It will also highlight some of the unanswered questions in this area that may warrant further investigation.
Many reports of associations between a wide variety of infectious
agents and atherosclerosis have recently appeared. An
exhaustive evaluation of each of these purported associations lies
beyond the scope of this survey. Rather, we will concentrate
particularly on two particular infectious agents, one viral and one
bacterial, currently linked with atherogenesis and supported by
emerging evidence. Specifically, this report will focus primarily on
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S. Kiechl, G. Egger, M. Mayr, C. J. Wiedermann, E. Bonora, F. Oberhollenzer, M. Muggeo, Q. Xu, G. Wick, W. Poewe, et al. Chronic Infections and the Risk of Carotid Atherosclerosis : Prospective Results From a Large Population Study Circulation, February 27, 2001; 103(8): 1064 - 1070. [Abstract] [Full Text] [PDF]
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L. Gullestad, H. Aass, J. G. Fjeld, L. Wikeby, A. K. Andreassen, H. Ihlen, S. Simonsen, J. Kjekshus, S. Nitter-Hauge, T. Ueland, et al. Immunomodulating Therapy With Intravenous Immunoglobulin in Patients With Chronic Heart Failure Circulation, January 16, 2001; 103(2): 220 - 225. [Abstract] [Full Text] [PDF]
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P. K. Shah Link Between Infection and Atherosclerosis: Who Are The Culprits: Viruses, Bacteria, Both, or Neither? Circulation, January 2, 2001; 103(1): 5 - 6. [Full Text] [PDF]
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R. G. J. Gibbs, M. Sian, A. W. M. Mitchell, R. M. Greenhalgh, A. H. Davies, and N. Carey Chlamydia pneumoniae Does Not Influence Atherosclerotic Plaque Behavior in Patients With Established Carotid Artery Stenosis Stroke, December 1, 2000; 31(12): 2930 - 2935. [Abstract] [Full Text] [PDF]
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J. B. Muhlestein, J. L. Anderson, J. F. Carlquist, K. Salunkhe, B. D. Horne, R. R. Pearson, T. J. Bunch, A. Allen, S. Trehan, and C. Nielson Randomized Secondary Prevention Trial of Azithromycin in Patients With Coronary Artery Disease : Primary Clinical Results of the ACADEMIC Study Circulation, October 10, 2000; 102(15): 1755 - 1760. [Abstract] [Full Text] [PDF]
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C. Espinola-Klein, H.-J. Rupprecht, S. Blankenberg, C. Bickel, H. Kopp, G. Rippin, G. Hafner, U. Pfeifer, and J. Meyer Are Morphological or Functional Changes in the Carotid Artery Wall Associated With Chlamydia pneumoniae, Helicobacter pylori, Cytomegalovirus, or Herpes Simplex Virus Infection? Stroke, September 1, 2000; 31(9): 2127 - 2133. [Abstract] [Full Text] [PDF]
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S. Fichtlscherer, G. Rosenberger, D. H. Walter, S. Breuer, S. Dimmeler, and A. M. Zeiher Elevated C-Reactive Protein Levels and Impaired Endothelial Vasoreactivity in Patients With Coronary Artery Disease Circulation, August 29, 2000; 102(9): 1000 - 1006. [Abstract] [Full Text] [PDF]
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D. G. Alber, K. L. Powell, P. Vallance, D. A. Goodwin, and C. Grahame-Clarke Herpesvirus Infection Accelerates Atherosclerosis in the Apolipoprotein E-Deficient Mouse Circulation, August 15, 2000; 102(7): 779 - 785. [Abstract] [Full Text] [PDF]
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J. M. Waugh, J. Li-Hawkins, E. Yuksel, M. D. Kuo, P. N. Cifra, P. R. Hilfiker, R. Geske, M. Chawla, J. Thomas, S. M. Shenaq, et al. Thrombomodulin Overexpression to Limit Neointima Formation Circulation, July 18, 2000; 102(3): 332 - 337. [Abstract] [Full Text] [PDF]
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G. Liuzzo, J. J. Goronzy, H. Yang, S. L. Kopecky, D. R. Holmes, R. L. Frye, and C. M. Weyand Monoclonal T-Cell Proliferation and Plaque Instability in Acute Coronary Syndromes Circulation, June 27, 2000; 101(25): 2883 - 2888. [Abstract] [Full Text] [PDF]
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P. K. Shah Circulating Markers of Inflammation for Vascular Risk Prediction : Are they Ready for Prime Time Circulation, April 18, 2000; 101(15): 1758 - 1759. [Full Text] [PDF]
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P. M. Ridker, N. Rifai, M. J. Stampfer, and C. H. Hennekens Plasma Concentration of Interleukin-6 and the Risk of Future Myocardial Infarction Among Apparently Healthy Men Circulation, April 18, 2000; 101(15): 1767 - 1772. [Abstract] [Full Text] [PDF]
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M. J Davies CORONARY DISEASE: The pathophysiology of acute coronary syndromes Heart, March 1, 2000; 83(3): 361 - 366. [Full Text]
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J. Willeit, S. Kiechl, F. Oberhollenzer, G. Rungger, G. Egger, E. Bonora, M. Mitterer, and M. Muggeo Distinct Risk Profiles of Early and Advanced Atherosclerosis : Prospective Results From the Bruneck Study Arterioscler Thromb Vasc Biol, February 1, 2000; 20(2): 529 - 537. [Abstract] [Full Text] [PDF]
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C. Urbich, M. Fritzenwanger, A. M. Zeiher, and S. Dimmeler Laminar Shear Stress Upregulates the Complement-Inhibitory Protein Clusterin : A Novel Potent Defense Mechanism Against Complement-Induced Endothelial Cell Activation Circulation, February 1, 2000; 101(4): 352 - 355. [Abstract] [Full Text] [PDF]
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M. Roivainen, M. Viik-Kajander, T. Palosuo, P. Toivanen, M. Leinonen, P. Saikku, L. Tenkanen, V. Manninen, T. Hovi, and M. Manttari Infections, Inflammation, and the Risk of Coronary Heart Disease Circulation, January 25, 2000; 101(3): 252 - 257. [Abstract] [Full Text] [PDF]
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C. Bartels, M. Maass, G. Bein, N. Brill, J. F. M. Bechtel, R. Leyh, and H.-H. Sievers Association of Serology With the Endovascular Presence of Chlamydia pneumoniae and Cytomegalovirus in Coronary Artery and Vein Graft Disease Circulation, January 18, 2000; 101(2): 137 - 141. [Abstract] [Full Text] [PDF]
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J. A. Ambrose and G. Dangas Unstable Angina: Current Concepts of Pathogenesis and Treatment Arch Intern Med, January 10, 2000; 160(1): 25 - 37. [Abstract] [Full Text] [PDF]
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A. Hoffmeister, D. Rothenbacher, P. Wanner, G. Bode, K. Persson, H. Brenner, V. Hombach, and W. Koenig Seropositivity to chlamydial lipopolysaccharide and chlamydia pneumoniae, systemic inflammation and stable coronary artery disease: Negative results of a case-control study J. Am. Coll. Cardiol., January 1, 2000; 35(1): 112 - 118. [Abstract] [Full Text] [PDF]
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A. Kol, A. H. Lichtman, R. W. Finberg, P. Libby, and E. A. Kurt-Jones Cutting Edge: Heat Shock Protein (HSP) 60 Activates the Innate Immune Response: CD14 Is an Essential Receptor for HSP60 Activation of Mononuclear Cells J. Immunol., January 1, 2000; 164(1): 13 - 17. [Abstract] [Full Text] [PDF]
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W. Koenig, D. Rothenbacher, A. Hoffmeister, M. Miller, G. Bode, G. Adler, V. Hombach, W. Marz, M. B. Pepys, and H. Brenner Infection With Helicobacter pylori Is Not a Major Independent Risk Factor for Stable Coronary Heart Disease : Lack of a Role of Cytotoxin-Associated Protein A-Positive Strains and Absence of a Systemic Inflammatory Response Circulation, December 7, 1999; 100(23): 2326 - 2331. [Abstract] [Full Text] [PDF]
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C. J. Wiedermann, S. Kiechl, S. Dunzendorfer, P. Schratzberger, G. Egger, F. Oberhollenzer, and J. Willeit Association of endotoxemia with carotid atherosclerosis and cardiovascular disease: Prospective results from the bruneck study J. Am. Coll. Cardiol., December 1, 1999; 34(7): 1975 - 1981. [Abstract] [Full Text] [PDF]
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T. Quaschning and C. Wanner The role of Chlamydia in coronary heart disease--fact or fiction? Nephrol. Dial. Transplant., December 1, 1999; 14(12): 2800 - 2803. [Full Text] [PDF]
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Z. Mallat, S. Besnard, M. Duriez, V. Deleuze, F. Emmanuel, M. F. Bureau, F. Soubrier, B. Esposito, H. Duez, C. Fievet, et al. Protective Role of Interleukin-10 in Atherosclerosis Circ. Res., October 15, 1999; 85 (8): e17 - e24. [Abstract] [Full Text] [PDF]
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P. Libby and P. M. Ridker Novel Inflammatory Markers of Coronary Risk : Theory Versus Practice Circulation, September 14, 1999; 100(11): 1148 - 1150. [Full Text] [PDF]
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G. M. Chisolm III, S. L. Hazen, P. L. Fox, and M. K. Cathcart The Oxidation of Lipoproteins by Monocytes-Macrophages. BIOCHEMICAL AND BIOLOGICAL MECHANISMS J. Biol. Chem., September 10, 1999; 274(37): 25959 - 25962. [Full Text] [PDF]
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C. Zellner, T. M. Chou, V. Pasceri, A. Maseri, G. Cammarota, G. Patti, L. Cuoco, A. Gasbarrini, R. L. Grillo, G. Fedeli, et al. Antibiotic Prophylaxis and Treatment of Cardiovascular Disease • Response Circulation, April 13, 1999; 99 (14): 1922 - 1926. [Full Text] [PDF]
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