Skip to main content

Advertisement

SpringerLink
Log in

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

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Higgins JP (2003) Chlamydia pneumoniae and coronary artery disease: the antibiotic trials. Mayo Clin Proc 78:321–332

    Article  PubMed  Google Scholar 

  2. Castelli W (1984) Epidemiology of coronary artery disease. Am J Med 76:4–12

    Article  PubMed  CAS  Google Scholar 

  3. Vojdani A (2003) A look at infectious agents as a possible causative factor in cardiovascular disease: part I. Lab Med 34:203–212

    Article  Google Scholar 

  4. Fong IW (2000) Emerging relations between infectious diseases and coronary artery disease and atherosclerosis. CMAJ 163:49–56

    PubMed  CAS  Google Scholar 

  5. Cunningham P (2000) Is coronary artery disease an infectious disease? J Inf Pharmacother 2:320–325

    Google Scholar 

  6. LaBiche R, Koziol D, Quinn TC et al (2001) Presence of Chlamydia pneumoniae in human symptomatic and asymptomatic carotid atherosclerotic plaque. Stroke 32:855–860

    Article  PubMed  CAS  Google Scholar 

  7. DeGraba TJ (2004) Immunogenetic susceptibility of atherosclerotic stroke implications on current and future treatment of vascular inflammation. Stroke 35:2712–2719

    Article  PubMed  CAS  Google Scholar 

  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 100:1569–1575

    PubMed  CAS  Google Scholar 

  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 97:633–636

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  11. Cochran WG (1954) The combination of estimates from different experiments. Biometrics 10:101–129

    Article  Google Scholar 

  12. Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748

    PubMed  CAS  Google Scholar 

  13. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188

    Article  PubMed  CAS  Google Scholar 

  14. Tobias A (1999) Assessing the influence of a single study in the meta-analysis estimate. Stata Tech Bull 8:15–17

    Google Scholar 

  15. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in metaanalysis detected by a simple, graphical test. BMJ 315:629–634

    Article  PubMed  CAS  Google Scholar 

  16. Cour MI, López de Atalaya FJ et al (1989) Lack of serological association between herpesvirus and atherosclerosis. Lancet 1:279

    Article  PubMed  CAS  Google Scholar 

  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 64:359–362

    Article  PubMed  CAS  Google Scholar 

  18. Balk AH, Weimar W, Rothbarth PH et al (1993) Passive immunization against cytomegalovirus in allograft recipients. The Rotterdam Heart Transplant Program experience. Infection 21:195–200

    Article  PubMed  CAS  Google Scholar 

  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 94:922–927

    PubMed  CAS  Google Scholar 

  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 35:741–743

    CAS  Google Scholar 

  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 10:233

    Google Scholar 

  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 35:351–352

    Google Scholar 

  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 177:209–212

    Article  PubMed  CAS  Google Scholar 

  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 82:1479–1483

    Article  PubMed  CAS  Google Scholar 

  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 120:93–99

    Article  PubMed  CAS  Google Scholar 

  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 32:35–41

    Article  PubMed  CAS  Google Scholar 

  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 81:866–868

    Article  PubMed  CAS  Google Scholar 

  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 14:79–80

    Google Scholar 

  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 98:2796–2799

    PubMed  CAS  Google Scholar 

  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 81:245–247

    PubMed  CAS  Google Scholar 

  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 40:275–280

    Article  PubMed  CAS  Google Scholar 

  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 179:690–692

    Article  PubMed  CAS  Google Scholar 

  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 81:248–251

    PubMed  CAS  Google Scholar 

  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 18:245–247

    Google Scholar 

  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 15:230

    CAS  Google Scholar 

  36. Su M, Bian YS, Wang ML (1999) The relationship between Cytomegalovirus Infection and Coronary heart disease [in Chinese]. Chin J Intern Med 38:13

    Google Scholar 

  37. Ammarm P, Maarsehall S, Kraus M et al (2000) Characteristics and prognosis of myocardial infarction in patients with normal coronary arteries. Chest 117:333–338

    Article  Google Scholar 

  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 15:148–150

    Google Scholar 

  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 8:154–156

    Google Scholar 

  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 102:2335–2340

    PubMed  CAS  Google Scholar 

  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 6:237–239

    Google Scholar 

  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 8:263–265

    Google Scholar 

  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 15:211–212

    Google Scholar 

  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 8:210–211

    Google Scholar 

  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 17:270–276

    PubMed  CAS  Google Scholar 

  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 17:70–72

    Google Scholar 

  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 21:427–432

    Article  PubMed  CAS  Google Scholar 

  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 160:457–463

    Article  PubMed  Google Scholar 

  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 163:149–156

    Article  PubMed  CAS  Google Scholar 

  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 13:170–177

    Article  PubMed  Google Scholar 

  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 92:515–521

    Article  PubMed  CAS  Google Scholar 

  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 10:859–860

    Google Scholar 

  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 11:102–106

    PubMed  Google Scholar 

  54. Timóteo A, Ferreira J, Paixão P et al (2003) Serologic markers for cytomegalovirus in acute coronary syndromes. Rev Port Cardiol 22:619–631

    PubMed  Google Scholar 

  55. Chen R, Xiong S, Yang Y et al (2003) The relationship between human cytomegalovirus infection and atherosclerosis development. Mol Cell Biochem 249:91–96

    Article  PubMed  CAS  Google Scholar 

  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 8:5982–5983

    CAS  Google Scholar 

  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 40:1123–1130

    Article  PubMed  Google Scholar 

  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 91:19–22

    Article  PubMed  CAS  Google Scholar 

  59. Sun Y, Pei W, Welte T et al (2005) Cytomegalovirus infection is associated with elevated interleukin-10 in coronary artery disease. Atherosclerosis 179:133–137

    Article  PubMed  CAS  Google Scholar 

  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 46:205–209

    Article  PubMed  CAS  Google Scholar 

  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. 19:149–151

    PubMed  CAS  Google Scholar 

  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 22:788–789

    Google Scholar 

  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 54:446–454

    Article  PubMed  CAS  Google Scholar 

  64. Gredmark S, Jonasson L, Van Gosliga D et al (2007) Active cytomegalovirus replication in patients with coronary disease. Scand Cardiovasc J 41:230–234

    Article  PubMed  CAS  Google Scholar 

  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 23:390–396

    Article  PubMed  Google Scholar 

  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 18:529–530

    Google Scholar 

  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 48:403–406

    PubMed  Google Scholar 

  68. Wang WM (2011) Increased IL-10 correlated with human cytomegalovirus infection in patients with coronary heart disease [in Chinese]. J Guiyang Hosp TCM 33:52–56

    Google Scholar 

  69. Alavi SM, Adel SM, Rajabzadeh AR (2011) An evidence against the effect of chronic cytomegalovirus infection in unstable angina pectoris. Acta Med Iran 49:78–80

    PubMed  Google Scholar 

  70. Bodurtha J, Adler SP, Nance WE (1988) Seroepidemiology of cytomegalovirus and herpes simplex virus in twins and their families. Am J Epidemiol 128:268–276

    PubMed  CAS  Google Scholar 

  71. Benditt EP, Barrett T, McDougal JK (1993) Viruses in the etiology of atherosclerosis. Proc Natl Acad Sci USA 80:6386–6389

    Article  Google Scholar 

  72. Minick CR, Fabricant CG, Fabricant J, Litrenta MM (1979) Athero-arteriosclerosis induced by infection with a herpesvirus. Am J Pathol 96:673–706

    PubMed  CAS  Google Scholar 

  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 47:69–75

    Article  PubMed  Google Scholar 

  74. Kowalski M, Pawlik M, Konturek JW, Konturek SJ (2006) Helicobacter pylori infection in coronary artery disease. J Physiol Pharmacol 57:101–111

    PubMed  Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Jiangsu Province Hospital of Traditional Chinese Medicine, 155 Hanzhong Road, Nanjing, 210029, China

    Ya-Nan Ji

  2. Department of Gerontology, Affiliated Zhongda Hospital, Southeast University, 87 Dingjiaqiao, Nanjing, 210009, China

    Li An

  3. First Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing University School of Medicine, 215 Guangzhou Road, Nanjing, 210029, China

    Ping Zhan

  4. Department of Cardiology, Jiangsu Province Hospital of Traditional Chinese Medicine, 155 Hanzhong Road, Nanjing, 210029, China

    Xiao-Hu Chen

Authors
  1. Ya-Nan Ji
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Li An
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ping Zhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiao-Hu Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Ping Zhan or Xiao-Hu Chen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ji, YN., An, L., Zhan, P. et al. Cytomegalovirus infection and coronary heart disease risk: a meta-analysis. Mol Biol Rep 39, 6537–6546 (2012). https://doi.org/10.1007/s11033-012-1482-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-012-1482-6

Keywords

Search

Navigation