Molecular Biology Reports

, Volume 39, Issue 6, pp 6537–6546 | Cite as

Cytomegalovirus infection and coronary heart disease risk: a meta-analysis

  • Ya-Nan Ji
  • Li An
  • Ping Zhan
  • Xiao-Hu Chen


The chronic inflammatory process including cytomegalovirus (CMV) infection has been hypothesized to induce the progression of atherosclerosis in coronary heart disease (CHD). Numbers studies were conducted to analyze the association between CMV infection and risk of CHD, but no clear consensus had been reached. To assess this relationship more precisely, a meta-analysis was performed. The electronic databases PubMed, Embase, and CNKI were searched; data were extracted and analyzed independently by two investigators. Ultimately, 55 studies, involving 9,000 cases and 8,608 controls from six prospective studies (all with a nested case–control design) and 49 retrospective case–control studies were included. Overall, people exposed to CMV infection had an odds ratio (OR) of 1.67 (95% CI, 1.56–1.79) for CHD risk, relative to those not exposed. CMV infection was clearly identified as a risk factor for CHD in both prospective studies (OR, 1.31; 95% CI, 1.132–1.517) and retrospective studies (OR, 1.79; 95% CI, 1.659–1.939), and in both Asian group (OR, 2.69; 95% CI, 2.304–3.144) and non-Asian group (OR, 1.48; 95% CI, 1.371–1.600). Interestingly, in the subgroup analyses by detection methods of CMV, the increased risk (OR, 8.121) was greater among studies using polymerase chain reaction than the risk (OR, 1.561) among studies using enzyme-linked immunosorbent assay. In conclusion, this meta-analysis suggested that CMV infection is associated with an increased risk for CHD, especially among Asian populations.


Cytomegalovirus Infection Coronary heart disease Meta-analysis 


Conflict of interest



  1. 1.
    Higgins JP (2003) Chlamydia pneumoniae and coronary artery disease: the antibiotic trials. Mayo Clin Proc 78:321–332PubMedCrossRefGoogle Scholar
  2. 2.
    Castelli W (1984) Epidemiology of coronary artery disease. Am J Med 76:4–12PubMedCrossRefGoogle Scholar
  3. 3.
    Vojdani A (2003) A look at infectious agents as a possible causative factor in cardiovascular disease: part I. Lab Med 34:203–212CrossRefGoogle Scholar
  4. 4.
    Fong IW (2000) Emerging relations between infectious diseases and coronary artery disease and atherosclerosis. CMAJ 163:49–56PubMedGoogle Scholar
  5. 5.
    Cunningham P (2000) Is coronary artery disease an infectious disease? J Inf Pharmacother 2:320–325Google Scholar
  6. 6.
    LaBiche R, Koziol D, Quinn TC et al (2001) Presence of Chlamydia pneumoniae in human symptomatic and asymptomatic carotid atherosclerotic plaque. Stroke 32:855–860PubMedCrossRefGoogle Scholar
  7. 7.
    DeGraba TJ (2004) Immunogenetic susceptibility of atherosclerotic stroke implications on current and future treatment of vascular inflammation. Stroke 35:2712–2719PubMedCrossRefGoogle Scholar
  8. 8.
    Zhou YF, Shou M, Guetta E et al (1999) Cytomegalovirus infection of rats increases the neointimal response to vascular injury without consistent evidence of direct infection of the vascular wall. Circulation 100:1569–1575PubMedGoogle Scholar
  9. 9.
    Muhlestein JB, Anderson JL, Hammond EH et al (1998) Infection with Chlamydia pneumoniae accelerates the development of atherosclerosis and treatment with azithromycin prevents it in a rabbit model. Circulation 97:633–636PubMedGoogle Scholar
  10. 10.
    Adam E, Melnick JL, Probtsfield JL et al (1987) High levels of cytomegalovirus antibody in patients requiring vascular surgery for atherosclerosis. Lancet 2:291–293PubMedCrossRefGoogle Scholar
  11. 11.
    Cochran WG (1954) The combination of estimates from different experiments. Biometrics 10:101–129CrossRefGoogle Scholar
  12. 12.
    Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748PubMedGoogle Scholar
  13. 13.
    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188PubMedCrossRefGoogle Scholar
  14. 14.
    Tobias A (1999) Assessing the influence of a single study in the meta-analysis estimate. Stata Tech Bull 8:15–17Google Scholar
  15. 15.
    Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in metaanalysis detected by a simple, graphical test. BMJ 315:629–634PubMedCrossRefGoogle Scholar
  16. 16.
    Cour MI, López de Atalaya FJ et al (1989) Lack of serological association between herpesvirus and atherosclerosis. Lancet 1:279PubMedCrossRefGoogle Scholar
  17. 17.
    McDonald K, Rector TS, Braulin EA et al (1989) Association of coronary artery disease in cardiac transplant recipients with cytomegalovirus infection. Am J Cardiol 64:359–362PubMedCrossRefGoogle Scholar
  18. 18.
    Balk AH, Weimar W, Rothbarth PH et al (1993) Passive immunization against cytomegalovirus in allograft recipients. The Rotterdam Heart Transplant Program experience. Infection 21:195–200PubMedCrossRefGoogle Scholar
  19. 19.
    Nieto FJ, Adam E, Sorlie P et al (1996) Cohort study of cytomegalovirus infection as a risk factor for carotid intimal-medial thickening, a measure of subclinical atherosclerosis. Circulation 94:922–927PubMedGoogle Scholar
  20. 20.
    Li BQ, Xu C, Wang Q et al (1996) The detection of the antibodies of human cytomegalovirus in sera of patients with coronary heart disease [in Chinese]. Chin J Intern Med 35:741–743Google Scholar
  21. 21.
    Shan JK, Li LY, Li G (1996) The Preliminary report on the detection of Cytomegalovirus antibody in coronary heart disease [in Chinese]. Pract Geriatr 10:233Google Scholar
  22. 22.
    Zhao L, Shao LH, Yang YP et al (1997) Study of Human Cytomegalovirus antibody level in Patients with coronary heart diseases [in Chinese]. Acta Acad Med Shandong 35:351–352Google Scholar
  23. 23.
    Adler SP, Hur JK, Wang JP (1998) Prior infection with cytomegalovirus is not a major risk factor for angiographically demonstrated coronary artery atherosclerosis. J Infect Dis 177:209–212PubMedCrossRefGoogle Scholar
  24. 24.
    Fang JC, Kinlay S, Kundsin R et al (1998) Chlamydia pneumoniae infection is frequent but not associated with coronary arteriosclerosis in cardiac transplant recipients. Am J Cardiol 82:1479–1483PubMedCrossRefGoogle Scholar
  25. 25.
    Ossewaarde JM, Feskens EJ, De Vries A et al (1998) Chlamydia pneumoniae is a risk factor for coronary heart disease in symptom-free elderly men, but Helicobacter pylori and cytomegalovirus are not. Epidemiol Infect 120:93–99PubMedCrossRefGoogle Scholar
  26. 26.
    Anderson JL, Carlquist JF, Muhlestein JB et al (1998) 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 32:35–41PubMedCrossRefGoogle Scholar
  27. 27.
    Blum A, Giladi M, Weinberg M et al (1998) High anti-cytomegalovirus (CMV) IgG antibody titer is associated with coronary artery disease and may predict post-coronary balloon angioplasty restenosis. Am J Cardiol 81:866–868PubMedCrossRefGoogle Scholar
  28. 28.
    Feng JX, Bao GL, Jiang XF et al (1998) The detection of cytomegalovirus in the peripheral blood cells of patients with coronary heart disease [in Chinese]. J Clin Cardiol 14:79–80Google Scholar
  29. 29.
    Ridker PM, Hennekens CH, Stampfer MJ et al (1998) Prospective study of herpes simplex virus, cytomegalovirus, and the risk of future myocardial infarction and stroke. Circulation 98:2796–2799PubMedGoogle Scholar
  30. 30.
    Danesh J, Wong Y, Ward M et al (1999) Chronic infection with Helicobacter pylori, Chlamydia pneumoniae, or cytomegalovirus: population based study of coronary heart disease. Heart 81:245–247PubMedGoogle Scholar
  31. 31.
    Kaftan HA, Kaftan O, Kiliç M (1999) Markers of chronic infection and inflammation. Are they important in cases with chronic coronary heart disease. Jpn Heart J 40:275–280PubMedCrossRefGoogle Scholar
  32. 32.
    Rothenbacher D, Hoffmeister A, Bode G et al (1999) Cytomegalovirus infection and coronary heart disease: results of a german case-control study. J Infect Dis 179:690–692PubMedCrossRefGoogle Scholar
  33. 33.
    Strachan DP, Carrington D, Mendall MA et al (1999) Cytomegalovirus seropositivity and incident ischaemic heart disease in the Caerphilly prospective heart disease study. Heart 81:248–251PubMedGoogle Scholar
  34. 34.
    Huang CX, Li GS, Li JJ et al (1999) Relationship of cytomegalovirus infection and coronary heart disease [in Chinese]. J Chin Cardiovasc Pulm Dis 18:245–247Google Scholar
  35. 35.
    Li JJ, Huang CX, Li GS (1999) Significance and detection of human cytomegalovirus dna in patients with coronary heart disease [in Chinese]. J Clin cardiol 15:230Google Scholar
  36. 36.
    Su M, Bian YS, Wang ML (1999) The relationship between Cytomegalovirus Infection and Coronary heart disease [in Chinese]. Chin J Intern Med 38:13Google Scholar
  37. 37.
    Ammarm P, Maarsehall S, Kraus M et al (2000) Characteristics and prognosis of myocardial infarction in patients with normal coronary arteries. Chest 117:333–338CrossRefGoogle Scholar
  38. 38.
    Bai L, Ma AQ, Yan H (2000) A preliminary study on antiphospholipid antibody in coronary heart disease and its relation [in Chinese]. Chin Circ J 15:148–150Google Scholar
  39. 39.
    Chen YF, Du XQ, Cai YY et al (2000) The Clinical Significance of Detection of Human Cytomegalovirus in Patients with Coronary Heart Dieases [in Chinese]. Chin J Arterioscler 8:154–156Google Scholar
  40. 40.
    Siscovick DS, Schwartz SM, Corey L et al (2000) 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 102:2335–2340PubMedGoogle Scholar
  41. 41.
    Dong Y, Sun X, Ning B et al (2000) Assessment of serology for detection of chlamydia pneumoniae and cytomegalovirus in patients with acute coronary syndrome [in Chinese]. S Chin J Cardiol 6:237–239Google Scholar
  42. 42.
    Hu LW, Liu JZ, Niu SQ et al (2000) Prevalence of present cytomegalovirus in the atherosclerosis arterial walls and leucocytes of the patients with coronary heart disease [in Chinese]. Chin J Arterioscler 8:263–265Google Scholar
  43. 43.
    Song WQ, Yao L, Zhang Z (2000) Clinical significance of detection of serum HCMV and AECA antibody [in Chinese]. Shanghai J Med Lab Sci 15:211–212Google Scholar
  44. 44.
    Du XQ, Cai YY, Chen YF et al (2000) Clinical significance of detection of human cytomegalovirus infection in patients with acute coronary syndrome [in Chinese]. Chin J Hypertens 8:210–211Google Scholar
  45. 45.
    Smieja M, Cronin L, Levine M et al (2001) Previous exposure to Chlamydia pneumoniae, Helicobacter pylori and other infections in Canadian patients with ischemic heart disease. Can J Cardiol 17:270–276PubMedGoogle Scholar
  46. 46.
    Deng HP, Wang ZH, Dong JH (2001) Significance and mechanism of human cytomegalovirus infection in coronary atherosclerotic heart disease [in Chinese]. J Clin Cardiol 17:70–72Google Scholar
  47. 47.
    Hoffmeister A, Rothenbacher D, Bode G et al (2001) Current infection with Helicobacter pylori, but not seropositivity to Chlamydia pneumoniae or cytomegalovirus, is associated with an atherogenic, modified lipid profile. Arterioscler Thromb Vasc Biol 21:427–432PubMedCrossRefGoogle Scholar
  48. 48.
    De Backer J, Mak R, De Bacquer D et al (2002) Parameters of inflammation and infection in a community based case-control study of coronary heart disease. Atherosclerosis 160:457–463PubMedCrossRefGoogle Scholar
  49. 49.
    Bloemenkamp DG, Mali WP, Tanis BC et al (2002) Chlamydia pneumoniae, Helicobacter pylori and cytomegalovirus infections and the risk of peripheral arterial disease in young women. Atherosclerosis 163:149–156PubMedCrossRefGoogle Scholar
  50. 50.
    Witherell HL, Smith KL, Friedman GD et al (2003) C-reactive protein, Helicobacter pylori, Chlamydia pneumoniae, cytomegalovirus and risk for myocardial infarction. Ann Epidemiol 13:170–177PubMedCrossRefGoogle Scholar
  51. 51.
    Georges JL, Rupprecht HJ, Blankenberg S et al (2003) AtheroGene Group. Impact of pathogen burden in patients with coronary artery disease in relation to systemic inflammation and variation in genes encoding cytokines. Am J Cardiol 92:515–521PubMedCrossRefGoogle Scholar
  52. 52.
    Sun YR, Guo JR, Liu GL (2003) Clinical study of the relationship between human cytomegalovirus infection and coronary heart disease [in Chinese]. Chin J Prim Med Pharm 10:859–860Google Scholar
  53. 53.
    Altannavch Ts, Roubalová K, Broz J et al (2003) Serological markers of Chlamydia pneumoniae, cytomegalovirus and Helicobacter pylori infection in diabetic and non-diabetic patients with unstable angina pectoris. Cent Eur J Public Health 11:102–106PubMedGoogle Scholar
  54. 54.
    Timóteo A, Ferreira J, Paixão P et al (2003) Serologic markers for cytomegalovirus in acute coronary syndromes. Rev Port Cardiol 22:619–631PubMedGoogle Scholar
  55. 55.
    Chen R, Xiong S, Yang Y et al (2003) The relationship between human cytomegalovirus infection and atherosclerosis development. Mol Cell Biochem 249:91–96PubMedCrossRefGoogle Scholar
  56. 56.
    Tang XD, Zhu QF, Zhou KY (2004) Human cytomegalovirus infection: an independent risk factor of coronary heart disease [in Chinese]. Chin J Clin Rehabil 8:5982–5983Google Scholar
  57. 57.
    Arcari CM, Gaydos CA, Nieto FJ et al (2005) Association between Chlamydia pneumoniae and acute myocardial infarction in young men in the United States military: the importance of timing of exposure measurement. Clin Infect Dis 40:1123–1130PubMedCrossRefGoogle Scholar
  58. 58.
    Sheehan J, Kearney PM, Sullivan SO et al (2005) Acute coronary syndrome and chronic infection in the Cork coronary care case-control study. Heart 91:19–22PubMedCrossRefGoogle Scholar
  59. 59.
    Sun Y, Pei W, Welte T et al (2005) Cytomegalovirus infection is associated with elevated interleukin-10 in coronary artery disease. Atherosclerosis 179:133–137PubMedCrossRefGoogle Scholar
  60. 60.
    Eryol NK, Kiliç H, Gül A et al (2005) Are the high levels of cytomegalovirus antibodies a determinant in the development of coronary artery disease? Int Heart J 46:205–209PubMedCrossRefGoogle Scholar
  61. 61.
    Wang XM, Li Y, Huang C et al (2005) Changes of serum soluble P-selectin and tumor necrotic factor-alpha in patients with CMV induced acute coronary syndrome [in Chinese]. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 19:149–151PubMedGoogle Scholar
  62. 62.
    Liu JG, Yang QL, Ji HB et al (2006) Antigen test results and clinical significance of Cytomegalovirus in peripheral blood of patients with coronary heart disease [in Chinese]. Prac J Med 22:788–789Google Scholar
  63. 63.
    Kaehler J, Tuleweit A, Steven D et al (2006) Association between eotaxin (CCL11), C-reactive protein, and antimicrobial antibodies in patients undergoing coronary angioplasty. J Investig Med 54:446–454PubMedCrossRefGoogle Scholar
  64. 64.
    Gredmark S, Jonasson L, Van Gosliga D et al (2007) Active cytomegalovirus replication in patients with coronary disease. Scand Cardiovasc J 41:230–234PubMedCrossRefGoogle Scholar
  65. 65.
    Jha HC, Prasad J, Mittal A (2008) High immunoglobulin A seropositivity for combined Chlamydia pneumoniae, Helicobacter pylori infection, and high-sensitivity C-reactive protein in coronary artery disease patients in India can serve as atherosclerotic marker. Heart Vessels 23:390–396PubMedCrossRefGoogle Scholar
  66. 66.
    Guo T, Xu YH, Wang ZH et al (2008) The clinical study of human cytomegalovirus infection in patients with coronary heart disease [in Chinese]. Southwest Def Med 18:529–530Google Scholar
  67. 67.
    Safaie N, Ghotaslou R, Montazer Ghaem H (2010) Seroprevalence of cytomegalovirus in patients with and without coronary artery diseases at Madani Heart Center, Iran. Acta Med Iran 48:403–406PubMedGoogle Scholar
  68. 68.
    Wang WM (2011) Increased IL-10 correlated with human cytomegalovirus infection in patients with coronary heart disease [in Chinese]. J Guiyang Hosp TCM 33:52–56Google Scholar
  69. 69.
    Alavi SM, Adel SM, Rajabzadeh AR (2011) An evidence against the effect of chronic cytomegalovirus infection in unstable angina pectoris. Acta Med Iran 49:78–80PubMedGoogle Scholar
  70. 70.
    Bodurtha J, Adler SP, Nance WE (1988) Seroepidemiology of cytomegalovirus and herpes simplex virus in twins and their families. Am J Epidemiol 128:268–276PubMedGoogle Scholar
  71. 71.
    Benditt EP, Barrett T, McDougal JK (1993) Viruses in the etiology of atherosclerosis. Proc Natl Acad Sci USA 80:6386–6389CrossRefGoogle Scholar
  72. 72.
    Minick CR, Fabricant CG, Fabricant J, Litrenta MM (1979) Athero-arteriosclerosis induced by infection with a herpesvirus. Am J Pathol 96:673–706PubMedGoogle Scholar
  73. 73.
    Van Dam-Mieras MC, Bruggeman CA, Muller AD, Debie WH, Zwaal RF (1987) Induction of endothelial cell procoagulant activity by cytomegalovirus infection. Thromb Res 47:69–75PubMedCrossRefGoogle Scholar
  74. 74.
    Kowalski M, Pawlik M, Konturek JW, Konturek SJ (2006) Helicobacter pylori infection in coronary artery disease. J Physiol Pharmacol 57:101–111PubMedGoogle Scholar

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© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  1. 1.Jiangsu Province Hospital of Traditional Chinese MedicineNanjingChina
  2. 2.Department of Gerontology, Affiliated Zhongda HospitalSoutheast UniversityNanjingChina
  3. 3.First Department of Respiratory Medicine, Nanjing Chest HospitalNanjing University School of MedicineNanjingChina
  4. 4.Department of CardiologyJiangsu Province Hospital of Traditional Chinese MedicineNanjingChina

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