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Biomarkers of Infection and Risk of Coronary Heart Disease

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Part of the book series: Contemporary Cardiology ((CONCARD))

Abstract

Chronic infection has been found to be significantly associated with the development of atherosclerosis and the clinical complications of unstable angina, myocardial infarction, and stroke. A variety of infectious agents have been proposed to be involved in atherothrombosis, and, indeed, the number of implicated agents continues to increase each year. These include specific bacterial and viral agents, as well as a variety of agents associated with periodontal disease. However, failure to confirm initial reports of serological associations also has been common. The infectious agents with the most evidence to support an etiological role in atherosclerosis include Chlamydia pneumoniae and cytomegalovirus. In addition, evidence is mounting for a variety of other potential agents including other herpes viruses, influenza, other specific bacteria (such as Mycoplasma pneumoniae), and chronic infections with common bacterial agents (e.g., periodontal disease, chronic bronchitis, chronic urinary tract infection). Nevertheless, specific causative relationships on par with that determined between Helicobacter pylori and peptic ulcer disease have not yet been established. In addition, treatment of some of these pathogens has failed to reduce the risk of cardiovascular complications. Future studies are expected to elucidate further the pathophysiological relationship between chronic infection and atherosclerosis and the potential of a variety of treatment approaches including antibiotics. Until then, however, a general recommendation for the use of any of these infectious markers during routine cardiovascular risk stratification cannot be made.

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References

  1. Farmer JA, Gotto AM Jr. Dyslipidemia and other risk factors for coronary artery disease. In: Braunwald E, ed. Heart Disease: A Textbook of Cardiovascular Medicine, 5th ed. WB Saunders, Philadelphia, 1997, pp. 1126–1160.

    Google Scholar 

  2. Wilson PW, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation 1998;97(18):1837–1847.

    PubMed  CAS  Google Scholar 

  3. Grayston IT, Kuo C-C, Campbell LA, Wang S-P. Chlamydia pneumoniae sp. Nov. for Chlamydia sp strain TWAR. Int J Syst Bacteriol 1989;39:88–90.

    Article  Google Scholar 

  4. Grayston IT, Campbell LA, Kuo C-C, et al. A new respiratory tract pathogen: Chlamydia pneumoniae strain TWAR. J Infect Dis 1990;161:618–625.

    PubMed  CAS  Google Scholar 

  5. Beatty WL, Morrison RP, Byrne GI. Persistent chlamydiae: from cell culture to a paradigm for chlamydial pathogenesis. Microbiol Rev 1994;58(4):686–699.

    PubMed  CAS  Google Scholar 

  6. Saikku P, Mattila K, Nieminen MS, et al. Serological evidence of an association of a novel Chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarction. Lancet 1998;2(8618): 983–986.

    Google Scholar 

  7. Saikku P, Leinonen M, Tenkanen L, et al. Chronic Chlamydia pneumoniae infection as a risk factor for coronary heart disease in the Helsinki heart study. Ann Intern Med 1992;116:273–278.

    PubMed  CAS  Google Scholar 

  8. Anderson JL, Carlquist JF, Muhlestein JB, Horne BD, Elmer SP. Evaluation of C-reactive protein, an inflammatory marker, and infectious serology as risk factors for coronary artery disease and myocardial infarction. J Am Coll Cardiol 1998;32(1):35–41.

    Article  PubMed  CAS  Google Scholar 

  9. Dowell SF, Peeling RW, Boman J, et al. Standardizing Chlamydia pneumoniae assays: recommendations from the Centers for Disease Control and Prevention (USA) and the Laboratory Centre for Disease Control (Canada). Clin Infect Dis 2001;33:492–502.

    Article  PubMed  CAS  Google Scholar 

  10. Boman J, Soderberg S, Forsberg J, et al. High prevalence of Chlamydia pneumoniae DNA in peripheral blood mononuclear cells in patients with cardiovascular disease and in middle-aged blood donors. J Infec Dis 1998;178(1):274–277.

    Article  CAS  Google Scholar 

  11. Muhlestein JB, Carlquist JF, Hammond EH, et al. Detection of Chlamydia pneumoniae bacteremia in patients with symptomatic coronary atherosclerosis. J Invest Med 1997;45(1):142A.

    Google Scholar 

  12. Nyvad O, Larsen NA, Lokkegaard N, Pedersen RS, Solling J, Pedersen EB. Chlamydia pneumoniae DNA in peripheral blood mononuclear cells in dialysis patients, renal transplant recipients and healthy controls. Scand J Clin Lab Invest 2002;62(7):503–509.

    Article  PubMed  Google Scholar 

  13. Smieja M, Mahony J, Petrich A, Boman J, Chernesky M. Association of circulating Chlamydia pneumoniae DNA with cardiovascular disease: a systematic review. BMC Infect Dis 2002;2(1):21.

    Article  PubMed  Google Scholar 

  14. Freidank HM, Lux A, Dern P, Meyer-Konig U, Els T. Chlamydia pneumoniae DNA in peripheral venous blood samples from patients with carotid artery stenosis. Eur J Clin Microbiol Infect Dis 2002; 21(1):60–62.

    Article  PubMed  CAS  Google Scholar 

  15. Leowattana W, Pokum S, Mahanonda N, Poungvarin N. Rapid detection of Chlamydia pneumoniae DNA in peripheral blood mononuclear cells of coronary artery disease patients by real-time fluorescence PCR. J Med Assoc Thai 2002;84(Suppl 3):S658–S668.

    Google Scholar 

  16. Rassu M, Lauro FM, Cazzavillan S, et al. Detection of Chlamydia pneumoniae DNA in peripheral blood mononuclear cells of blood donors in the north-east of Italy. Med Microbiol Immun 2001;190(3): 139–144.

    CAS  Google Scholar 

  17. Sessa R, Di Pietro M, Schiavoni G, et al. Prevalence of Chlamydia pneumoniae in peripheral blood mononuclear cells in Italian patients with acute ischaemic heart disease. Atherosclerosis 2001;159(2): 521–525.

    Article  PubMed  CAS  Google Scholar 

  18. Smieja M, Chong S, Natarajan M, Petrich A, Rainen L, Mahony JB. Circulating nucleic acids of Chlamydia pneumoniae and cytomegalovirus in patients undergoing coronary angiography. J Clin Microbiol 2001;39(2):596–600.

    Article  PubMed  CAS  Google Scholar 

  19. Iliescu EA, Fiebig MF, Morton AR, Sankar-Mistry P. Chlamydia pneumoniae DNA in peripheral blood mononuclear cells in peritoneal dialysis patients. Peritoneal Dial Int 2000;20(6):722–726.

    CAS  Google Scholar 

  20. Kaul R, Uphoff J, Wiedeman J, Yadlapalli S, Wenman WM. Detection of Chlamydia pneumoniae DNA in CD3+ lymphocytes from healthy blood donors and patients with coronary artery disease. Circulation 2000;102(19):2341–2346.

    PubMed  CAS  Google Scholar 

  21. Mahony JB, Chong S, Coombes BK, Smieja M, Petrich A. Analytical sensitivity, reproducibility of results, and clinical performance of five PCR assays for detecting Chlamydia pneumoniae DNA in peripheral blood mononuclear cells. J Clin Microbiol 2000;38(7):2622–2627.

    PubMed  CAS  Google Scholar 

  22. Maass M, Jahn J, Gieffers J, Dalhoff K, Katus HA, Solbach W. Detection of Chlamydia pneumoniae within peripheral blood monocytes of patients with unstable angina or myocardial infarction. J Infect Dis 2000;181(Suppl 3):S449–S451.

    Article  PubMed  CAS  Google Scholar 

  23. Bodetti TJ, Timms P. Detection of Chlamydia pneumoniae DNA and antigen in the circulating mononuclear cell fractions of humans and koalas. Infect Immun 2000;68(5):2744–2747.

    Article  PubMed  CAS  Google Scholar 

  24. Blasi F, Boman J, Esposito G, et al. Chlamydia pneumoniae DNA detection in peripheral blood mononuclear cells is predictive of vascular infection. J Infect Dis 1999;180(6):2074–2076.

    Article  PubMed  CAS  Google Scholar 

  25. Boman J, Soderberg S, Forsberg J, et al. High prevalence of Chlamydia pneumoniae DNA in peripheral blood mononuclear cells in patients with cardiovascular disease and in middle-aged blood donors. J Infect Dis 1998;178(1):274–277.

    Article  PubMed  CAS  Google Scholar 

  26. Shor A, Kuo C-C, Patton DL. Detection of Chlamydia pneumoniae in coronary arterial fatty streaks and atherosclerotic plaques. S Afr Med J 1992;82:158–161.

    PubMed  CAS  Google Scholar 

  27. Muhlestein JB, Hammond EH, Carlquist JF, et al. Increased incidence of Chlamydia species within the coronary arteries of patients with symptomatic atherosclerotic versus other forms of cardiovascular disease. J Am Coll Cardiol 1996;27:1555–1561.

    Article  PubMed  CAS  Google Scholar 

  28. Jackson LA, Campbell LA, Kuo CC, Rodriguez DI, Lee A, Grayston JT. Isolation of Chlamydia pneumoniae from a carotid endarterectomy specimen. J Infect Dis 1997;176(1):292–295.

    Article  PubMed  CAS  Google Scholar 

  29. Ramirez JA. Isolation of Chlamydia pneumoniae from the coronary artery of a patient with coronary atherosclerosis. The Chlamydia pneumoniae/Atherosclerosis Study Group. Ann Intern Med 1996;12(12):979–982.

    Google Scholar 

  30. Fong IW, Chiu B, Vira E, Fong MW, Jang D, Mahony J. Rabbit model for Chlamydia pneumoniae infection. J Clin Microbiol 1997:35(1):48–52.

    PubMed  CAS  Google Scholar 

  31. Laitinen K, Laurila A, Pyhala L, Leinonen M, Saikku P. Chlamydia pneumoniae infection induces inflammatory changes in the aortas of rabbits. Infect Immun 1997;65(11):4832–4835.

    PubMed  CAS  Google Scholar 

  32. Muhlestein JB, Anderson JL, Hammond EF, et al. Infection with Chlamydia pneumoniae accelerates the development of atherosclerosis and treatment with azithromycin prevents it in a rabbit model. Circulation 1998;97:633–636.

    PubMed  CAS  Google Scholar 

  33. Moazed TC, Kuo C, Grayston JT, Campbell LA. Murine models of Chlamydia pneumoniae infection and atherosclerosis. J Infect Dis 1997;175(4):883–890.

    Article  PubMed  CAS  Google Scholar 

  34. Hu H, Pierce GN, Zhong G. The atherogenic effects of chlamydia are dependent on serum cholesterol and specific to Chlamydia pneumoniae. J Clin Invest 1999;103(5):747–753.

    Article  PubMed  CAS  Google Scholar 

  35. Saikku P, Laitinen K, Leinonen M. Animal models for Chlamydia pneumoniae infection. Atherosclerosis 1998;140(Suppl 1):S17–S19.

    Article  PubMed  CAS  Google Scholar 

  36. Liuba P, Karnani P, Pesonen E, et al. Endothelial dysfunction after repeated Chlamydia pneumoniae infection in apolipoprotein E-knockout mice. Circulation 2000;102(9):1039–1044.

    PubMed  CAS  Google Scholar 

  37. Aalto-Setala K, Laitinen K, Erkkila L, et al. Chlamydia pneumoniae does not increase atherosclerosis in the aortic root of apolipoprotein E-deficient mice. Arterioscl Thromb Vasc Biol 2001;21(4):578–584.

    PubMed  CAS  Google Scholar 

  38. Blessing E, Lin TM, Campbell LA, Rosenfeld ME, Lloyd D, Kuo C. Chlamydia pneumoniae induces inflammatory changes in the heart and aorta of normocholesterolemic C57BL/6J mice. Infect Immun 2000;68(8):4765–4768.

    Article  PubMed  CAS  Google Scholar 

  39. Gupta S, Leatham EW, Carrington D, Mendall MA, Kaski JC. Elevated Chlamydia pneumoniae antibodies, cardiovascular events, and azithromycin in male survivors of myocardial infarction. Circulation 1997;96(2):404–407.

    PubMed  CAS  Google Scholar 

  40. Gurfinkel E, Bozovich G, Daroca A, Beck E, Mautner B. Randomised trial of roxithromycin in non-Qwave coronary syndromes: ROXIS Pilot Study. ROXIS Study Group. Lancet 1997;350(9075):404–407.

    Article  PubMed  CAS  Google Scholar 

  41. Gurfinkel E, Bozovich G, Beck E, Testa E, Livellara B, Mautner B. Treatment with the antibiotic roxithromycin in patients with acute non-Q-wave coronary syndromes: the final report of the ROXIS Study. Eur Heart J 1999;20(2):121–127.

    Article  PubMed  CAS  Google Scholar 

  42. Anderson JL, Muhlestein JB, Carlquist J, et al. Randomized secondary prevention trial of azithromycin in patients with coronary artery disease and serological evidence for Chlamydia pneumoniae infection. The azithromycin in coronary artery disease: elimination of myocardial infection with Chlamydia (ACADEMIC) study. Circulation 1999;99:1540–1547.

    PubMed  CAS  Google Scholar 

  43. Muhlestein JB, Anderson JL, Carlquist JF, et al. Randomized secondary prevention trial of azithromycin in patients with coronary artery disease: primary clinical results of the ACADEMIC study. Circulation 2000;102:1755–1760.

    PubMed  CAS  Google Scholar 

  44. Neumann F, Kastrati A, Miethke T, et al. Treatment of Chlamydia pneumoniae infection with roxithromycin and effect on neointima proliferation after coronary stent placement (ISAR-3): a randomised, double-blind, placebo-controlled trial. Lancet 2001;357(9274):2085–2089.

    Article  PubMed  CAS  Google Scholar 

  45. Stone AFM, Mendall M, Kaski J-C, Gupta S, Camm J, Northfield T. Antibiotics against Chlamydia pneumoniae and Helicobacter pylori reduce further cardiovascular events in patients with acute coronary syndromes. J Am Coll Cardiol 2001;37(2A):349A.

    Google Scholar 

  46. Dunne MW. Rationale and design of a secondary prevention trial of antibiotic use in patients after myocardial infarction: the WIZARD (weekly intervention with Zithromax [azithromycin] for atherosclerosis and its related disorders) trial. J Infect Dis 2000;181(Suppl 3):S572–S578.

    Article  PubMed  CAS  Google Scholar 

  47. Coletta A, Thackray S, Nikitin N, Cleland JG. Clinical trials update: highlights of the scientific sessions of The American College of Cardiology 2002: LIFE, DANAMI 2, MADIT-2, MIRACLE-ICD, OVERTURE, OCTAVE, ENABLE 1 & 2, CHRISTMAS, AFFIRM, RACE, WIZARD, AZACS, REMATCH, BNP trial and HARDBALL. Eur J Heart Failure 2002;4(3):381–388.

    Article  Google Scholar 

  48. Cercek B, Shah PK, Noc M, et al. Effect of short-term treatment with azithromycin on recurrent ischaemic events in patients with acute coronary syndrome in the Azithromycin in Acute Coronary Syndrome (AZACS) trial: a randomised controlled trial. Lancet 2003;361(9360):809–813.

    Article  PubMed  CAS  Google Scholar 

  49. Grayston JT. Secondary prevention antibiotic treatment trials for coronary artery disease. Circulation 2000;102(15):1742, 1743.

    PubMed  CAS  Google Scholar 

  50. Gieffers J, Füüllgraf H, Jahn J, et al. Chlamydia pneumoniae infection in circulating human monocytes is refractory to antibiotic treatment. Circulation 2000;103:351–356.

    Google Scholar 

  51. Goodwin CS, Worsley BW. Microbiology of Helicobacter pylori. Gastroenterol Clin N Am 1993;22:5–19.

    CAS  Google Scholar 

  52. Goodwin CS, Mendall MM, Northfield TC. Helicobacter pylori infection. Lancet 1997;349(9047):265–269.

    Article  PubMed  CAS  Google Scholar 

  53. Wisniewski RM, Peura DA. Helicobacter pylori: beyond peptic ulcer disease. Gastroenterologist 1997;5(4):295–305.

    PubMed  CAS  Google Scholar 

  54. Mendall MA, Goggin PM, Molineaux N, et al. Relation of Helicobacter pylori infection and coronary heart disease. Br Heart J 1994;71(5):437–439.

    Article  PubMed  CAS  Google Scholar 

  55. Danesh J, Collins R, Peto R. Chronic infections and coronary heart disease: is there a link? Lancet 1997; 350(9075):430–436.

    Article  PubMed  CAS  Google Scholar 

  56. Danesh J, Peto R. Risk factors for coronary heart disease and infection with Helicobacter pylori: metaanalysis of 18 studies. BMJ 1998;316(7138):1130–1132.

    PubMed  CAS  Google Scholar 

  57. Mendall MA, Patel P, Ballam L, Strachan D, Northfield TC. C reactive protein and its relation to cardiovascular risk factors: a population based cross sectional study. BMJ 1996;312(7038):1061–1065.

    PubMed  CAS  Google Scholar 

  58. Birnie DH, Holme ER, McKay IC, Hood S, McColl KE, Hillis WS. Association between antibodies to heat shock protein 65 and coronary atherosclerosis: possible mechanism of action of Helicobacter pylori and other bacterial infections in increasing cardiovascular risk. Eur Heart J 1998;19(3):387–394.

    Article  PubMed  CAS  Google Scholar 

  59. Pasceri V, Cammarota G, Patti G, et al. Circulation 1998;97(17):1675–1679.

    PubMed  CAS  Google Scholar 

  60. Mayr M, Kiechl S, Mendall MA, Willeit J, Wick G, Xu Q. Increased risk of atherosclerosis is confined to CagA-positive Helicobacter pylori strains: prospective results from the Bruneck study. Stroke 2003;34(3):610–615.

    Article  PubMed  Google Scholar 

  61. Kowalski M, Rees W, Konturek PC, et al. Detection of Helicobacter pylori specific DNA in human atheromatous coronary arteries and its association to prior myocardial infarction and unstable angina. Dig Liver Dis 2002;34(6):398–402.

    Article  PubMed  CAS  Google Scholar 

  62. (No authors listed). iCase Records of the Massachusetts General Hospital. Weekly clinicopathological exercises: case 39-1983. N Engl J Med 1983;309:782–789.

    Google Scholar 

  63. Taylor-Robinson D. Infections due to species of Mycoplasma and Ureaplasma: an update. Clin Infect Dis 1996;23:671–684.

    PubMed  CAS  Google Scholar 

  64. Luby JP. Pneumonia caused by Mycoplasma pneumoniae infection. Clin Chest Med 1991;12:237–244.

    PubMed  CAS  Google Scholar 

  65. Horne BD, Muhlestein JB, Carlquist JF, et al. IgA seropositivity to mycoplasma pneumoniae predicts the diagnosis of coronary artery disease. J Am Coll Cardiol 2000;35(2 Suppl A):312A.

    Google Scholar 

  66. Lim TH, Muhlestein JB, Carlquist JF, et al. Mycoplasma pneumoniae high IgA titer but not IgG predicts increased hazard of death or myocardial infarction among patients with angiographically-defined coronary artery disease. J Am Coll Cardiol 2002;39(5 Suppl A):327A.

    Article  Google Scholar 

  67. Higuchi M de L, Higuchi-Dos-Santos MH, Pierri H, et al. Mycoplasma pneumoniae and Chlamydia pneumoniae in calcified nodules of aortic stenotic valves. Revista Instituto Medicina Tropical Sao Paulo 2002;44(4):209–212.

    Google Scholar 

  68. Maraha B, Berg H, Scheffer GJ, et al. Correlation between detection methods of Chlamydia pneumoniae in atherosclerotic and non-atherosclerotic tissues. Diagn Microbiol Infect Dis 2001;39(3):139–143.

    Article  PubMed  CAS  Google Scholar 

  69. Churchill AE, Biggs PM. Herpes-type virus isolated in cell culture from tumors of chickens with Marek’s disease. II. Studies in vivo. J Natl Cancer Inst 1968;41(4):951–956.

    PubMed  CAS  Google Scholar 

  70. Minick CR, Fabricant CG, Fabricant J, Litrenta MM. Atheroarteriosclerosis induced by infection with a herpes virus. Am J Pathol 1979;96(3):673–706.

    PubMed  CAS  Google Scholar 

  71. Adam E, Melnick JL, Probtsfield JL, et al. High levels of cytomegalovirus antibody in patients requiring vascular surgery for atherosclerosis. Lancet 1987;2(8554):291–293.

    Article  PubMed  CAS  Google Scholar 

  72. Melnick JL, Hu C, Burek J, Adam E, DeBakey ME. Cytomegalovirus DNA in arterial walls of patients with atherosclerosis. J Med Virol 1994;42(2):170–174.

    Article  PubMed  CAS  Google Scholar 

  73. Grattan MT, Moreno-Cabral CE, Starnes VA, Oyer PE, Stinson EB, Shumway NE. Cytomegalovirus infection is associated with cardiac allograft rejection and atherosclerosis. JAMA 1989;261(24):3561–3566.

    Article  PubMed  CAS  Google Scholar 

  74. Muhlestein JB, Horne BD, Carlquist JF, et al. Cytomegalovirus seropositivity and C-reactive protein have independent and combined predictive value for mortality in patients with angiographically demonstrated coronary artery disease. Circulation 2000;102(16):1917–1923.

    PubMed  CAS  Google Scholar 

  75. Horne BD, Muhlestein JB, Carlquist JF, Renlund DG, Bair TL, Anderson JL. Cytomegalovirus: strength of antibody response and its relationship to risk of mortality among patients with angiographic coronary disease. J Am Coll Cardiol 2003;41(6 Suppl A):367A.

    Article  Google Scholar 

  76. Smieja M, Gnarpe J, Lonn E, et al. Heart Outcomes Prevention Evaluation (HOPE) Study Investigators. Multiple infections and subsequent cardiovascular events in the Heart Outcomes Prevention Evaluation (HOPE) Study. Circulation 2003;107(2):251–257.

    Article  PubMed  Google Scholar 

  77. Hajjar DP, Pomerantz KB, Falcone DJ, et al. Herpes simplex virus infection in human arterial cells: implications in arteriosclerosis. J Clin Invest 1987;80:1317–1321.

    Article  PubMed  CAS  Google Scholar 

  78. Visser MR, Vercellotti GM. Herpes simplex virus and atherosclerosis. Eur Heart J 1993;14:39–42.

    PubMed  Google Scholar 

  79. Key NS, Bach RR, Vercellotti GM, et al. Herpes simplex virus type I does not require productive infection to induce tissue factor in human umbilical vein endothelial cells. Lab Invest 1993;68:645–651.

    PubMed  CAS  Google Scholar 

  80. Span AH, van Dam-Mieras MC, Mullers W, et al. The effect of virus infection on the adherence of leukocytes or platelets to endothelial cells. Eur J Clin Invest 1991;21:331–338.

    Article  PubMed  CAS  Google Scholar 

  81. Visser MR, Jacob HS, Goodman JL, et al. Granulocyte-mediated injury to herpes simplex virus-infected human endothelium. Lab Invest 1989;60:296–304.

    PubMed  CAS  Google Scholar 

  82. Constans J, Marchand JM, Conri C, et al. Asymptomatic atherosclerosis in HIV-patients: a case control ultrasound study. Ann Med 1995;27:683–685.

    Article  PubMed  CAS  Google Scholar 

  83. Paton P, Tabib A, Loire R, Tete R. Coronary lesions and immunodeficiency virus infection. Res Virol 1993;144:225–231.

    Article  PubMed  CAS  Google Scholar 

  84. Spodick DH, Flessas AP, Johnson MM. Association of acute respiratory symptoms with onset of acute myocardial infarction: prospective investigation of 150 consecutive patients and matched control patients. Am J Cardiol 1984;53:481–482.

    Article  PubMed  CAS  Google Scholar 

  85. Bainton D, Jones GR, Hole D. Influenza and ischemic heart disease: a possible trigger for acute myocardial infarction? Int J Epidemiol 1978;7:231–239.

    Article  PubMed  CAS  Google Scholar 

  86. Zheng ZJ, Mittleman MA, Tofler GH, et al. Infections prior to acute MI onset. J Am Coll Cardiol 1998; 31(Suppl A):132A.

    Article  Google Scholar 

  87. Abinader EG, Sharif DS, Omary M. Inferior wall myocardial infarction preceded by acute exudative pharyngitis in young males. Isr J Med Sci 1993;29:764–769.

    PubMed  CAS  Google Scholar 

  88. Collins SD. Excess mortality from causes other than influenza and pneumonia during influenza epidemics. Public Health Rep 1932;47:2159–2180.

    Google Scholar 

  89. Naghavi M, Wyde P, Litovsky S, et al. Influenza infection exerts prominent inflammatory and thrombotic effects on the atherosclerotic plaques of apolipoprotein E-deficient mice. Circulation 2003;107(5):762–768.

    Article  PubMed  CAS  Google Scholar 

  90. Naghavi M, Barlas Z, Siadaty S, Naguib S, Madjid M, Casscells W. Association of influenza vaccination and reduced risk of recurrent myocardial infarction. Circulation 2000;102(25):3039–3045.

    PubMed  CAS  Google Scholar 

  91. Lavallée P, Perchaud V, Gautier-Bertrand M, Grabli D, Amarenco P. Association between influenza vaccination and reduced risk of brain infarction. Stroke 2002;33:513–518.

    Article  PubMed  Google Scholar 

  92. Jackson LA, Yu O, Heckbert SR, et al. Vaccine Safety Datalink Study Group. Influenza vaccination is not associated with a reduction in the risk of recurrent coronary events. Am J Epidemiol 2002;156(7): 634–640.

    Article  PubMed  Google Scholar 

  93. Gurfinkel EP, de la Fuente RL, Mendiz O, Mautner B. Influenza vaccine pilot study in acute coronary syndromes and planned percutaneous coronary interventions: the FLU Vaccination Acute Coronary Syndromes (FLUVACS) Study. Circulation 2002;105(18):2143–2147.

    Article  PubMed  Google Scholar 

  94. Epstein SE, Zhou YF, Zhu J. Infection and atherosclerosis: emerging mechanistic paradigms. Circulation 1999;100:e20–e28.

    PubMed  CAS  Google Scholar 

  95. Zhu J, Quyyumi AA, Norman JE, et al. Effects of total pathogen burden on coronary artery disease risk and C-reactive protein levels. Am J Cardiol 2000;85:140–146.

    Article  PubMed  CAS  Google Scholar 

  96. Zhu J, Nieto FJ, Horne BD, Anderson JL, Muhlestein JB, Epstein SE. Prospective study of pathogen burden and risk of myocardial infarction or death. Circulation 2001;103(1):45–51.

    PubMed  CAS  Google Scholar 

  97. Rupprecht HJ, Blankenberg S, Bickel C, et al. AutoGene Investigators. Impact of viral and bacterial infectious burden on long-term prognosis in patients with coronary artery disease. Circulation 2001;104(1):25–31.

    Article  PubMed  CAS  Google Scholar 

  98. Espinola-Klein C, Rupprecht HJ, Blankenberg S, et al. AtheroGene Investigators. Impact of infectious burden on extent and long-term prognosis of atherosclerosis. Circulation 2002,105(1):15–21.

    Article  PubMed  Google Scholar 

  99. Muhlestein JB, Anderson JL. Infectious serology and atherosclerosis: how burdensome is the risk? Circulation 2003;107(2):220–222.

    Article  PubMed  Google Scholar 

  100. Zhu J, Quyyumi AA, Norman JE, Csako G, Epstein SE. The possible role of hepatitis A virus in the pathogenesis of atherosclerosis. J Am Coll Cardiol 1999;33(2 Suppl A):4A.

    Google Scholar 

  101. Leinonen M, Linnanmaki E, Mattila K, et al. Circulating immune complexes containing chlamydial lipopolysaccharide in acute myocardial infarction. Microb Pathogen 1990;9(1):67–73.

    Article  CAS  Google Scholar 

  102. Thom DH, Wang SP, Grayston JT, et al. Chlamydia pneumoniae strain TWAR antibody and angiographically demonstrated coronary artery disease. Arterioscl Thromb 1991;11(3):547–551.

    PubMed  CAS  Google Scholar 

  103. Thom DH, Grayston JT, Siscovick DS, Wang SP, Weiss NS, Daling JR. Association of prior infection with Chlamydia pneumoniae and angiographically demonstrated coronary artery disease. JAMA 1992;268(1):68–72.

    Article  PubMed  CAS  Google Scholar 

  104. Linnanmaki E, Leinonen M, Mattila K, Nieminen MS, Valtonen V, Saikku P. Chlamydia pneumoniae specific circulating immune complexes in patients with chronic coronary heart disease. Circulation 1993; 87(4):1130–1134.

    PubMed  CAS  Google Scholar 

  105. Melnick SL, Shahar E, Folsom AR, et al. Past infection by Chlamydia pneumoniae strain TWAR and asymptomatic carotid atherosclerosis. Atherosclerosis Risk in Communities (ARIC) Study Investigators. Am J Med 1993;95(5):499–504.

    Article  PubMed  CAS  Google Scholar 

  106. Puolakkainen M, Kuo CC, Shor A, Wang SP, Grayston JT, Campbell LA. Serological response to Chlamydia pneumoniae in adults with coronary arterial fatty streaks and fibrolipid plaques. J Clin Microbiol 1993;31(8):2212–2214.

    PubMed  CAS  Google Scholar 

  107. Saikku P. Chlamydia pneumoniae infection as a risk factor in acute myocardial infarction. Eur Heart J 1993;14(Suppl K):S62.

    PubMed  Google Scholar 

  108. Dahlen GH, Boman J, Birgander LS, Lindblom B. Lp(a) lipoprotein, IgG, IgA and IgM antibodies to Chlamydia pneumoniae and HLA class II genotype in early coronary artery disease. Atherosclerosis 1995;114(2):165–174.

    Article  PubMed  CAS  Google Scholar 

  109. Mendall MA, Carrington D, Strachan D, et al. Chlamydia pneumoniae: risk factors for seropositivity and association with coronary heart disease. J Infect 1995;30(2):121–128.

    Article  PubMed  CAS  Google Scholar 

  110. Patel P, Mendall MA, Carrington D, et al. Association of Helicobacter pylori and Chlamydia pneumoniae infections with coronary heart disease and cardiovascular risk factors. BMJ 1995;311(7007):711–714.

    PubMed  CAS  Google Scholar 

  111. Cook PJ, Honeybourne D, Lip GY, Beevers DG, Wise R. Chlamydia pneumoniae and acute arterial thrombotic disease. Circulation 1995;92(10):3148, 3149.

    PubMed  CAS  Google Scholar 

  112. Miettinen H, Lehto S, Saikku P, et al. Association of Chlamydia pneumoniae and acute coronary heart disease events in non-insulin dependent diabetic and non-diabetic subjects in Finland. Eur Heart J 1996; 17(5):682–688.

    PubMed  CAS  Google Scholar 

  113. Wimmer ML, Sandmann-Strupp R, Saikku P, Haberl RL. Association of chlamydial infection with cerebrovascular disease. Stroke 1996;27(12):2207–2210.

    PubMed  CAS  Google Scholar 

  114. Ossewaarde JM, Feskens EJ, De Vries A, Vallinga CE, Kromhout D. Chlamydia pneumoniae is a risk factor for coronary heart disease in symptom-free elderly men, but Helicobacter pylori and cytomegalovirus are not. Epidemol Infect 1998;120(1):93–99.

    Article  CAS  Google Scholar 

  115. Gupta S, Leatham EW, Carrington D, Mendall MA, Kaski JC, Camm AJ. Elevated Chlamydia pneumoniae antibodies, cardiovascular events, and azithromycin in male survivors of myocardial infarction. Circulation 1997;96(2):404–407.

    PubMed  CAS  Google Scholar 

  116. Blasi F, Cosentini R, Raccanelli R, et al. A possible association of Chlamydia pneumoniae infection and acute myocardial infarction in patients younger than 65 years of age. Chest 1997;112(2):309–312.

    Article  PubMed  CAS  Google Scholar 

  117. Kark JD, Leinonen M, Paltiel O, Saikku P. Chlamydia pneumoniae and acute myocardial infarction in Jerusalem. Int J Epidemiol 1997;26(4):730–738.

    Article  PubMed  CAS  Google Scholar 

  118. Fagerberg B, Gnarpe J, Gnarpe H, Agewall S, Wikstrand J. Chlamydia pneumoniae but not cytomegalovirus antibodies are associated with future risk of stroke and cardiovascular disease: a prospective study in middle-aged to elderly men with treated hypertension. Stroke 1999;30(2):299–305.

    PubMed  CAS  Google Scholar 

  119. Miyashita N, Toyota E, Sawayama T, et al. Association of chronic infection of Chlamydia pneumoniae and coronary heart disease in the Japanese. Intern Med 1998;37(11):913–916.

    Article  PubMed  CAS  Google Scholar 

  120. Altman R, Rouvier J, Scazziota A, Absi RS, Gonzalez C. Lack of association between prior infection with Chlamydia pneumoniae and acute or chronic coronary artery disease. Clin Cardiol 1999;22(2):85–90.

    Article  PubMed  CAS  Google Scholar 

  121. Ridker PM, Kundsin RB, Stampfer MJ, Poulin S, Hennekens CH. Prospective study of Chlamydia pneumoniae IgG seropositivity and risks of future myocardial infarction. Circulation 1999;99(9):1161–1164.

    PubMed  CAS  Google Scholar 

  122. Siscovick DS, Schwartz SM, Corey L, et al. Chlamydia pneumoniae, herpes simplex virus type 1, and cytomegalovirus and incident myocardial infarction and coronary heart disease death in older adults: the Cardiovascular Health Study. Circulation 2000;102(19):2335–2340.

    PubMed  CAS  Google Scholar 

  123. Espinola-Klein C, Rupprecht HJ, Blankenberg S, et al. Are morphological or functional changes in the carotid artery wall associated with Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, or herpes simplex virus infection? Stroke 2000;31(9):2127–2133.

    PubMed  CAS  Google Scholar 

  124. Mayr M, Kiechl S, Willeit J, Wick G, Xu Q. Infections, immunity, and atherosclerosis: associations of antibodies to Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus with immune reactions to heat-shock protein 60 and carotid or femoral atherosclerosis. Circulation 2000;102(8):833–839.

    PubMed  CAS  Google Scholar 

  125. Kosaka C, Hara K, Komiyama Y, Takahashi H. Possible role of chronic infection with Chlamydia pneumoniae in Japanese patients with acute myocardial infarction. Jpn Circ J 2000;64(11):819–824.

    Article  PubMed  CAS  Google Scholar 

  126. Shimada K, Mokuno H, Watanabe Y, Sawano M, Daida H, Yamaguchi H. High prevalence of seropositivity for antibodies to Chlamydia-specific lipopolysaccharide in patients with acute coronary syndrome. J Cardiovasc Risk 2000;7(3):209–213.

    PubMed  CAS  Google Scholar 

  127. Tontsch D, Noll B, Schaefer JR, Herzum M, Maisch B, Goeke B. Hyperinsulinemia, lipoprotein (a), and Chlamydia pneumoniae antibodies—are they risk factors or serologic predictors for progression of coronary artery disease? Angiology 2000;51(10):831–836.

    Article  PubMed  CAS  Google Scholar 

  128. Hoffmeister A, Rothenbacher D, Wanner P, et al. 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 2000;35(1):112–128.

    Article  PubMed  CAS  Google Scholar 

  129. Song YG, Kwon HM, Kim JM, et al. Serologic and histopathologic study of Chlamydia pneumoniae infection in atherosclerosis: a possible pathogenetic mechanism of atherosclerosis induced by Chlamydia pneumoniae. Yonsei Med J 2000;41(3):319–327.

    PubMed  CAS  Google Scholar 

  130. Blanchard JF, Armenian HK, Peeling R, Friesen PP, Shen C, Brunham RC. The relation between Chlamydia pneumoniae infection and abdominal aortic aneurysm: case-control study. Clin Infect Dis 2000;30(6):946–947.

    Article  PubMed  CAS  Google Scholar 

  131. Wald NJ, Law MR, Morris JK, Zhou X, Wong Y, Ward ME. Chlamydia pneumoniae infection and mortality from ischaemic heart disease: large prospective study. BMJ 2000;321(7255):204–207.

    Article  PubMed  CAS  Google Scholar 

  132. Schmidt C, Hulthe J, Wikstrand J, et al. Chlamydia pneumoniae seropositivity is associated with carotid artery intima-media thickness. Stroke 2000;31(7):1526–1531.

    PubMed  CAS  Google Scholar 

  133. Elkind MS, Lin IF, Grayston JT, Sacco RL. Chlamydia pneumoniae and the risk of first ischemic stroke: the Northern Manhattan Stroke Study. Stroke 2000;31(7):1521–1525.

    PubMed  CAS  Google Scholar 

  134. Romeo F, Martuscelli E, Chirieolo G, et al. Seropositivity against Chlamydia pneumoniae in patients with coronary atherosclerosis. Clin Cardiol 2000;23(5):327–330.

    Article  PubMed  CAS  Google Scholar 

  135. Sharma N, Rutherford JD, Grayston JT, King LP, Jialal I, Andrews TC. Association between C-reactive protein, anti—Chlamydia pneumoniae antibodies, and vascular function in healthy adults. Am J Cardiol 2001;87(1):119–121, A9.

    Article  PubMed  CAS  Google Scholar 

  136. Smieja M, Cronin L, Levine M, Goldsmith CH, Yusuf S, Mahony JB. Previous exposure to Chlamydia pneumoniae, Helicobacter pylori and other infections in Canadian patients with ischemic heart disease. Can J Cardiol 2001;17(3):270–276.

    PubMed  CAS  Google Scholar 

  137. Katsenis C, Kouskouni E, Kolokotronis L, Rizos D, Dimakakos P. The significance of Chlamydia pneumoniae in symptomatic carotid stenosis. Angiology 2001;52(9):615–619.

    Article  PubMed  CAS  Google Scholar 

  138. Mendis S, Arseculeratne YM, Withana N, Samitha S. Chlamydia pneumoniae infection and its association with coronary heart disease and cardiovascular risk factors in a sample South Asian population. Int J Cardiol 2001;79(2–3):191–196.

    Article  PubMed  CAS  Google Scholar 

  139. Shimada K, Daida H, Mokuno H, et al. Association of seropositivity for antibody to Chlamydia-specific lipopolysaccharide and coronary artery disease in Japanese men. Jpn Circ JJ 2001;65(3):182–187.

    Article  PubMed  CAS  Google Scholar 

  140. Haubitz M, Brunkhorst R. C-reactive protein and chronic Chlamydia pneumoniae infection—long-term predictors for cardiovascular disease and survival in patients on peritoneal dialysis. Nephrol Dialysis Transplant 2001;16(4):809–815.

    Article  CAS  Google Scholar 

  141. Sander D, Winbeck K, Klingelhofer J, Etgen T, Conrad B. Enhanced progression of early carotid atherosclerosis is related to Chlamydia pneumoniae (Taiwan acute respiratory) seropositivity. Circulation 2001;103(10):1390–1395.

    PubMed  CAS  Google Scholar 

  142. Kuo CC, Shor A, Campbell LA, Fukushi H, Patton DL, Grayston JT. Demonstration of Chlamydia pneumoniae in atherosclerotic lesions of coronary arteries. J Infect Dis 1993;167(4):841–849.

    PubMed  CAS  Google Scholar 

  143. Davidson M, Kuo CC, Middaugh JP, et al. Confirmed previous infection with Chlamydia pneumoniae (TWAR) and its presence in early coronary atherosclerosis. Circulation 1998;98(7):628–633.

    PubMed  CAS  Google Scholar 

  144. Kuo CC, Coulson AS, Campbell LA, et al. Detection of Chlamydia pneumoniae in atherosclerotic plaques in the walls of arteries of lower extremities from patients undergoing bypass operation for arterial obstruction. J Vasc Surg 1997;26(1):29–31.

    Article  PubMed  CAS  Google Scholar 

  145. Jackson LA, Campbell LA, Kuo CC, Rodriguez DI, Lee A, Grayston JT. Isolation of Chlamydia pneumoniae from a carotid endarterectomy specimen. J Infect Dis 1997;176(1):292–295.

    Article  PubMed  CAS  Google Scholar 

  146. Jackson LA, Campbell LA, Schmidt RA, et al. Specificity of detection of Chlamydia pneumoniae in cardiovascular atheroma: evaluation of the innocent bystander hypothesis. Am J Pathol 1997;150(5):1785–1790.

    PubMed  CAS  Google Scholar 

  147. Grayston JT, Kuo CC, Coulson AS, et al. Chlamydia pneumoniae (TWAR) in atherosclerosis of the carotid artery. Circulation 1995;92(12):3397–3400.

    PubMed  CAS  Google Scholar 

  148. Campbell LA, O’Brien ER, Cappuccio A L, et al. Detection of Chlamydia pneumoniae TWAR in human coronary atherectomy tissues. J Infect Dis 1995;172(2):585–588.

    PubMed  CAS  Google Scholar 

  149. Kuo CC, Grayston JT, Campbell LA, Goo YA, Wissler RW, Benditt EP. Chlamydia pneumoniae (TWAR) in coronary arteries of young adults (15-34 years old). Proc Natl Acad Sci USA 1995;92(15):6911–6814.

    Article  PubMed  CAS  Google Scholar 

  150. Kuo CC, Gown AM, Benditt EP, Grayston JT. Detection of Chlamydia pneumoniae in aortic lesions of atherosclerosis by immunocytochemical stain. Arterioscl Thromb 1993;13(10):1501–1504.

    PubMed  CAS  Google Scholar 

  151. Shor A, Phillips JI, Ong G, Thomas BJ, Taylor-Robinson D. Chlamydia pneumoniae in atheroma: consideration of criteria for causality. J Clin Pathol 1998;51(11):812–817.

    Article  PubMed  CAS  Google Scholar 

  152. Maass M, Bartels C, Kruger S, Krause E, Engel PM, Dalhoff K. Endovascular presence of Chlamydia pneumoniae DNA is a generalized phenomenon in atherosclerotic vascular disease. Atherosclerosis 1998;140(Suppl 1):S25–S30.

    Article  PubMed  CAS  Google Scholar 

  153. Maass M, Gieffers J, Krause E, Engel PM, Bartels C, Solbach W. Poor correlation between microimmunofluorescence serology and polymerase chain reaction for detection of vascular Chlamydia pneumoniae infection in coronary artery disease patients. Med Microbiol Immunol 1998;187(2):103–106.

    Article  PubMed  CAS  Google Scholar 

  154. Wong Y, Thomas M, Tsang V, Gallagher PJ, Ward ME. The prevalence of Chlamydia pneumoniae in atherosclerotic and nonatherosclerotic blood vessels of patients attending for redo and first time coronary artery bypass graft surgery. J Am Coll Cardiol 1999;33(1):152–156.

    Article  PubMed  CAS  Google Scholar 

  155. Ouchi K, Fujii B, Kanamoto Y, Karita M, Shirai M, Nakazawa T. Chlamydia pneumoniae in coronary and iliac arteries of Japanese patients with atherosclerotic cardiovascular diseases. J Med Microbiol 1998;47(10):907–913.

    Article  PubMed  CAS  Google Scholar 

  156. Paterson DL, Hall J, Rasmussen SJ, Timms P. Failure to detect Chlamydia pneumoniae in atherosclerotic plaques of Australian patients. Pathology 1998;30(2):169–172.

    Article  PubMed  CAS  Google Scholar 

  157. Lindholt JS, Ostergard L, Henneberg EW, Fasting H, Andersen P. Failure to demonstrate Chlamydia pneumoniae in symptomatic abdominal aortic aneurysms by a nested polymerase chain reaction (PCR). Eur J Vasc Endovasc Surg 1998;15(2):161–164.

    Article  PubMed  CAS  Google Scholar 

  158. Juvonen J, Juvonen T, Laurila A, et al. Demonstration of Chlamydia pneumoniae in the walls of abdominal aortic aneurysms. J Vasc Surg 1997;25(3):499–505.

    Article  PubMed  CAS  Google Scholar 

  159. Blasi F, Denti F, Erba M, et al. Detection of Chlamydia pneumoniae but not Helicobacter pylori in atherosclerotic plaques of aortic aneurysms. J Clin Microbiol 1996;34(11):2766–2769.

    PubMed  CAS  Google Scholar 

  160. Weiss SM, Roblin PM, Gaydos CA, et al. Failure to detect Chlamydia pneumoniae in coronary atheromas of patients undergoing atherectomy. J Infect Dis 1996;173(4):957–962.

    PubMed  CAS  Google Scholar 

  161. Yamashita K, Ouchi K, Shirai M, Gondo T, Nakazawa T, Ito H. Distribution of Chlamydia pneumoniae infection in the atherosclerotic carotid artery. Stroke 1998;29(4):773–778.

    PubMed  CAS  Google Scholar 

  162. Wong Y, Thomas M, Tsang V, Gallagher PJ, Ward ME. The prevalence of Chlamydia pneumoniae in atherosclerotic and nonatherosclerotic blood vessels of patients attending for redo and first time coronary artery bypass graft surgery. J Am Coll Cardiol 1999;33(1):152–156.

    Article  PubMed  CAS  Google Scholar 

  163. Virok D, Kis Z, Karai L, et al. Chlamydia pneumoniae in atherosclerotic middle cerebral artery. Stroke 2001;32(9):1973–1976.

    Article  PubMed  CAS  Google Scholar 

  164. Grattan et al. Clin Cardiol 1991;14:16–20.

    Article  Google Scholar 

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Muhlestein, J.B. (2006). Biomarkers of Infection and Risk of Coronary Heart Disease. In: Morrow, D.A. (eds) Cardiovascular Biomarkers. Contemporary Cardiology. Humana Press. https://doi.org/10.1007/978-1-59745-051-5_20

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