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Weighing the evidence for infection as a risk factor for coronary heart disease

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Abstract

There has been considerable attention in recent years to the intriguing hypothesis that coronary heart disease and other atherosclerotic diseases may be caused by infection with pathogens such as Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus. Supporting this hypothesis are studies that localize bacterial antigens to atherosclerotic plaques and that draw associations of systemic inflammation and chronic infections with coronary disease. Although there are several examples of positive associations of pathogen seropositivity with disease, recent prospective follow-up studies of infection seropositivity have not generally supported these associations. At present, the evidence is insufficient to designate infection as a causal risk factor for coronary heart disease. The results of ongoing larger observational studies and antibiotic treatment trials may yield important information regarding the presence and magnitude of risk, if any, beyond that conferred by established coronary risk factors.

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References and Recommended Reading

  1. American Heart Association: 2000 Heart and Stroke Statistical Update. Dallas: American Heart Association; 2000.

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  4. Patel P, Mendall MA, Carrington D, et al.: Association of Helicobacter pylori and Chlamydia pneumoniae infections with coronary heart disease and cardiovascular risk factors. Br Med J 1995, 311:711–714.

    CAS  Google Scholar 

  5. Cook PJ, Honeybourne D, Lip GY, et al.: Chlamydia pneumoniae antibody titers are significantly associated with acute stroke and transient cerebral ischemia: the West Birmingham Stroke Project. Stroke 1998, 29:404–410.

    PubMed  CAS  Google Scholar 

  6. Ridker PM, Kundsin RB, Stampfer MJ, et al.: Prospective study of Chlamydia pneumoniae IgG seropositivity and risks of future myocardial infarction. Circulation 1999, 99:1161–1164. Absence of an association of C. pneumoniae seropositivity with MI in a nested, prospective case-control study of 343 cases and 343 matched controls drawn from a cohort of over 15,000 male physicians.

    PubMed  CAS  Google Scholar 

  7. Ridker PM, Hennekens CH, Buring JE, et al.: Baseline IgG antibody titers to Chlamydia pneumoniae, Helicobacter pylori, herpes simplex virus, and cytomegalovirus and the risk for cardiovascular disease in women. Ann Intern Med 1999, 131:573–577. Absence of an association of seropositivity to C. pneumoniae, H. pylori, herpes simplex virus, or CMV with cardiovascular disease in a nested, prospective case-control study of 122 cases and 244 matched controls drawn from a cohort of over 28,000 post-menopausal female health professionals.

    PubMed  CAS  Google Scholar 

  8. Ridker PM, Hennekens CH, Stampfer MJ, Wang F: Prospective study of herpes simplex virus, cytomegalovirus, and the risk of future myocardial infarction and stroke. Circulation 1998, 98:2796–2799. Absence of an association of herpes simplex virus and CMV seropositivity with MI or stroke in a nested, prospective case-control study of 643 cases and 643 matched controls drawn from a cohort of over 15,000 male physicians.

    PubMed  CAS  Google Scholar 

  9. Haider AW, Wilson PWF, Larson MG, et al.: Association of H Pylori, C Pneumoniae and Cytomegalovirus Seropositivity with Cardiovascular Disease in the Framingham Heart Study [abstract]. Circulation 1999, 100:1–232. Absence of an association of seropositivity to C. pneumoniae, H. pylori, or CMV with cardiovascular disease in a population-based, prospective cohort study of 1187 men and women drawn from a community cohort of over 5000 persons.

    Google Scholar 

  10. Libby P, Egan D, Skarlatos S: Roles of infectious agents in atherosclerosis and restenosis: an assessment of the evidence and need for future research. Circulation 1997, 96:4095–4103.

    PubMed  CAS  Google Scholar 

  11. 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 

  12. Chiu B: Multiple infections in carotid atherosclerotic plaques. Am Heart J 1999, 138:S534-S536.

    Article  PubMed  CAS  Google Scholar 

  13. Maass M, Bartels C, Kruger S, et al.: Endovascular presence of Chlamydia pneumoniae DNA is a generalized phenomenon in atherosclerotic vascular disease. Atherosclerosis1998, 140(suppl 1):S25-S30.

    Article  PubMed  CAS  Google Scholar 

  14. Kol A, Sukhova GK, Lichtman AH, Libby P: Chlamydial heat shock protein 60 localizes in human atheroma and regulates macrophage tumor necrosis factor-alpha and matrix metalloproteinase expression. Circulation 1998, 98:300–307.

    PubMed  CAS  Google Scholar 

  15. Kol A, Bourcier T, Lichtman AH, Libby P: Chlamydial and human heat shock protein 60s activate human vascular endothelium, smooth muscle cells, and macrophages. J Clin Invest 1999, 103:571–577.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  17. Danesh J, Collins R, Appleby P, Peto R: Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies. JAMA 1998, 279:1477–1482.

    Article  PubMed  CAS  Google Scholar 

  18. Lowe GD, Machado SG, Krol WF, et al.: White blood cell count and haematocrit as predictors of coronary recurrence after myocardial infarction. Thromb Haemost 1985, 54:700–703.

    PubMed  CAS  Google Scholar 

  19. Schlant RC, Forman S, Stamler J, Canner PL: The natural history of coronary heart disease: prognostic factors after recovery from myocardial infarction in 2789 men. The 5-year findings of the coronary drug project. Circulation 1982, 66:401–414.

    PubMed  CAS  Google Scholar 

  20. Lloyd-Jones DM, Camargo CA, Giugliano RP, O'Donnell CJ: Effect of leukocytosis at presentation on prognosis in patients with primary unstable angina. Am Heart J 2000, in press.

  21. Kannel WB, Anderson K, Wilson PW: White blood cell count and cardiovascular disease. Insights from the Framingham Study. JAMA 1992, 267:1253–1256.

    Article  PubMed  CAS  Google Scholar 

  22. Ridker PM, Cushman M, Stampfer MJ, et al.: Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997, 336:973–979.

    Article  PubMed  CAS  Google Scholar 

  23. Wilson PWF, D'Agostino RB, Levy D, et al.: Prediction of coronary heart disease using risk factor categories. Circulation 1998, 97:1837–1847.

    PubMed  CAS  Google Scholar 

  24. O'Donnell CJ, Larson MG, Benjamin E, et al.: Relationship of C-reactive protein to coronary and aortic calcification in the Framingham Heart Study [abstract]. Circulation 2000, 101:713–714.

    Google Scholar 

  25. Haider AW, Larson MG, O'Donnell CJ, et al.: The association of chronic cough with the risk of myocardial infarction: the Framingham Heart Study. Am J Med 2000, 106:279–284.

    Article  Google Scholar 

  26. Beck JD, Offenbacher S, Williams R, Gibbs P, Garcia R: Periodontitis: a risk factor for coronary heart disease? Ann Periodontol 1998, 3:127–141.

    PubMed  CAS  Google Scholar 

  27. Christen WG, Hennekens CH, Ajani UA, et al.: Periodontal disease and risks of cardiovascular disease [abstract]. Circulation 1998, 97:821.

    Google Scholar 

  28. 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. Cross-sectional data raising the hypothesis that burden of antecedent infections may be associated with increased risks for coronary artery atherosclerosis.

    Article  PubMed  CAS  Google Scholar 

  29. Ossewaarde JM, Feskens EJ, De Vries A, et al.: Chlamydia pneumoniae is a risk factor for coronary heart disease in symptom-free elderly men, but Helicobacter pylori and cytomegalovirus are not. Epidemiol Infect 1998, 120:93–99.

    Article  PubMed  CAS  Google Scholar 

  30. Roivainen M, Viik-Kajander M, Palosuo T, et al.: Infections, inflammation, and the risk of coronary heart disease. Circulation 2000, 101:252–257.

    PubMed  CAS  Google Scholar 

  31. Gupta S, Leatham EW, Carrington D, et al.: Elevated Chlamydia pneumoniae antibodies, cardiovascular events, and azithromycin in male survivors of myocardial infarction. Circulation 1997, 96:404–407.

    PubMed  CAS  Google Scholar 

  32. 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 

  33. 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, 17:682–688.

    PubMed  CAS  Google Scholar 

  34. Whincup PH, Mendall MA, Perry IJ, et al.: Prospective relations between Helicobacter pylori infection, coronary heart disease, and stroke in middle aged men. Heart 1996, 75:568–572.

    PubMed  CAS  Google Scholar 

  35. Strandberg TE, Tilvis RS, Vuoristo M, et al.: Prospective study of Helicobacter pylori seropositivity and cardiovascular diseases in a general elderly population. Br Med J 1997, 314:1317–1318.

    CAS  Google Scholar 

  36. Fagerberg B, Gnarpe J, Gnarpe H, et al.: 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, 30:299–305.

    PubMed  CAS  Google Scholar 

  37. Epstein SE, Zhu J: Lack of association of infectious agents with risk of future myocardial infarction and stroke: definitive evidence disproving the infection/coronary artery disease hypothesis [editorial]? Circulation 1999, 100:1366–1368.

    PubMed  CAS  Google Scholar 

  38. Meier CR, Derby LE, Jick SS, et al.: Antibiotics and risk of subsequent first-time acute myocardial infarction. JAMA 1999, 281:427–431.

    Article  PubMed  CAS  Google Scholar 

  39. 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. Lowering of levels of serum markers of inflammation associated with randomization to azithromycin in 302 patients with coronary artery disease seropositive to C. pneumoniae, with no associated reduction in CHD outcomes.

    PubMed  CAS  Google Scholar 

  40. Gurfinkel E, Bozovich G, Daroca A, et al.: Randomised trial of roxithromycin in non-Q-wave coronary syndromes: ROXIS Pilot Study. ROXIS Study Group. Lancet 1997, 350:404–407.

    Article  PubMed  CAS  Google Scholar 

  41. Gurfinkel E, Bozovich G, Beck E, et al.: 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, 20:121–127. Presence of a significant reduction in CHD outcomes at the end of the treatment period (30 days) associated with randomization to roxithromycin, but absence of significant differences in outcomes at 90 days and 180 days.

    Article  PubMed  CAS  Google Scholar 

  42. Grayston JT, Jackson LA, Kennedy WJ, Kronmal RA: Secondary prevention trials for coronary artery disease with antibiotic treatment for Chlamydia pneumoniae: design issues. Am Heart J 1999, 138:S545-S549.

    Article  PubMed  CAS  Google Scholar 

  43. Dunne M: WIZARD and the design of trials for secondary prevention of atherosclerosis with antibiotics. Am Heart J 1999, 138:S542-S544.

    Article  PubMed  CAS  Google Scholar 

  44. O'Donnell CJ, Kannel WB: Cardiovascular risks of hypertension: lessons from observational studies. J Hypertens Suppl 1998, 16(Suppl 6):S3-S7.

    PubMed  Google Scholar 

  45. Murray CJ, Lopez AD: Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study. Lancet 1997, 349:1498–1504.

    Article  PubMed  CAS  Google Scholar 

  46. Nieto FJ, Folsom AR, Sorlie PD, et al.: Chlamydia pneumoniae infection and incident coronary heart disease: the Atherosclerosis Risk in Communities Study. Am J Epidemiol 1999, 150:149–156.

    PubMed  CAS  Google Scholar 

  47. Folsom AR, Nieto FJ, Sorlie PD, et al.: Helicobacter pylori seropositivity and coronary heart disease incidence. Atherosclerosis Risk in Communities (ARIC) Study Investigators. Circulation 1998, 98:845–850.

    PubMed  CAS  Google Scholar 

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  1. Framingham Heart Study, 5 Thurber Street, 01702, Framingham, MA, USA

    Christopher J. O'Donnell MD MPH & Daniel Levy MD

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  1. Christopher J. O'Donnell MD MPH
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  2. Daniel Levy MD
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O'Donnell, C.J., Levy, D. Weighing the evidence for infection as a risk factor for coronary heart disease. Curr Cardiol Rep 2, 280–287 (2000). https://doi.org/10.1007/s11886-000-0082-6

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  • DOI: https://doi.org/10.1007/s11886-000-0082-6

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