Inflammation Research

, Volume 61, Issue 6, pp 591–598 | Cite as

Association of influenza virus infection and inflammatory cytokines with acute myocardial infarction

  • Xiuru Guan
  • Wei Yang
  • Xijuan Sun
  • Lanfeng Wang
  • Benjiang Ma
  • Hongyuan Li
  • Jin ZhouEmail author
Original Research Paper



To explore the potential relationship between previous influenza virus (IV) infection and acute myocardial infarction (AMI), and the mechanism of atherosclerosis, we conducted a case–control study and examined inflammatory cytokines to assess the association of previous IV infection and AMI.


A questionnaire-based survey was conducted to collect information about demographic characteristics and heart disease risk factors. Fasting blood samples were obtained to measure immunoglobulin (Ig) G antibodies to influenza virus A (IV-A), influenza virus B (IV-B), cytomegalovirus, herpes simplex virus type-1 and type-2, adenovirus, rubella virus and Chlamydia pneumoniae, and to measure the level of certain biochemistry markers: interleukin-2, 6, 10 and 18 (IL-2, 6, 10 and 18), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), endothelin-1 (ET-1), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1).


Compared with the controls, the cases were more likely to have positive IgG antibodies to IV-A and IV-B [IV-A: odds ratio (OR): 3.1, 95% confidence interval (CI): 1.5–6.4; IV-B: OR: 10.2, 95% CI: 5.7–20.0]. After adjustment for potential confounding variables, the risk of AMI was still associated with the presence of IgG antibodies to IV-A (adjusted OR: 5.5, 95% CI: 1.3–23.0) and IV-B (adjusted OR: 20.3, 95% CI: 5.6–40.8). The levels of IL-2, 6, 10 and18, TNF-α, IFN-γ, ET-1, sICAM-1 and sVCAM-1 in patients with AMI were significantly higher than those of the controls (P < 0.01).


Our study supports the hypothesis that previous IV infection is associated with AMI. Inflammatory cytokines may take part in the development of atherosclerosis and trigger the occurrence of AMI.


Influenza virus Infection Atherosclerosis Inflammatory cytokine Acute myocardial infarction 



Thanks are extended to the staff of the Medical Examination Center and the Cardiac Care Unit of the First Hospital of Harbin Medical University for their assistance. We acknowledge Dr. Wei-Min Li for his clinical advice to this study. Acknowledgement was extended to Li-Xin Jiang, Chun-Yan Lin, Lian-Ming Wang, Zhao-Zhen Xu and Li-Yan Wang for their laboratory tests and survey. This study was supported by the Natural Science Foundation (grant D200968) of Heilongjiang Province in China.

Conflict of interest

No author has any conflict of interest.

Supplementary material

11_2012_449_MOESM1_ESM.doc (31 kb)
Supplementary material 1 (DOC 31 kb)


  1. 1.
    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;102:3039–45.PubMedGoogle Scholar
  2. 2.
    Ross R. Atherosclerosis: an inflammatory disease. N Engl J Med. 1999;340(2):115–26.PubMedCrossRefGoogle Scholar
  3. 3.
    Saikku P. Seroepidemiology in Chlamydia pneumoniae–atherosclerosis association. Eur Heart J. 2002;23(4):263–4.PubMedCrossRefGoogle Scholar
  4. 4.
    Oshima T, Ozono R, Yano Y, Oishi Y, Teragawa H, Higashi Y, et al. Association of Helicobacter pylori infection with systemic inflammation and endothelial dysfunction in healthy male subjects. J Am Coll Cardiol. 2005;45:1219–22.PubMedCrossRefGoogle Scholar
  5. 5.
    Badiou S, Thiebaut R, Aurillac-Lavignolle V, Dabis F, Laporte F, Cristol JP, et al. Groupe d’Epidémiologie Clinique du Sida en Aquitaine (GECSA). Association of non-HDL cholesterol with subclinical atherosclerosis in HIV-positive patients. J Infect. 2008;57(1):47–54.PubMedCrossRefGoogle Scholar
  6. 6.
    Calza L, Manfredi R, Pocaterra D, Chiodo F. Risk of premature atherosclerosis and ischemic heart disease associated with HIV infection and antiretroviral therapy. J Infect. 2008;57(1):16–32.PubMedCrossRefGoogle Scholar
  7. 7.
    Chiu B. Multiple infections in carotid atherosclerotic plaques. Am Heart J. 1999;138(5 Pt 2):S534–6.PubMedCrossRefGoogle Scholar
  8. 8.
    Nieto FJ, Adam E, Sorlie P, Farzadegan H, Melnick JL, Comstock GW, et al. Cohort study of cytomegalovirus infection as a risk factor for carotid intimal–medial thickening, a measure of subclinical atherosclerosis. Circulation. 1996;94(5):922–7.PubMedGoogle Scholar
  9. 9.
    Siscovick DS, Schwartz SM, Corey L, Grayston JT, Ashley R, Wang SP, 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;102:2335–40.PubMedGoogle Scholar
  10. 10.
    Zhu J, Quyyumi AA, Norman JE, Costello R, Csako G, Epstein SE. The possible role of hepatitis A virus in the pathogenesis of atherosclerosis. J Infect Dis. 2000;182(6):1583–7.PubMedCrossRefGoogle Scholar
  11. 11.
    Auer J, Berent R, Weber T, Eber B. Influenza virus infection, infectious burden, and atherosclerosis. Stroke. 2002;33(2):1454–5.PubMedCrossRefGoogle Scholar
  12. 12.
    Lavallée P, Perchaud V, Gautier-Bertrand M, Grabli D, Amarenco P. Association between influenza vaccination and reduced risk of brain infarction. Stroke. 2002;33:513–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Auer J, Leitinger M, Berent R, Prammer W, Weber T, Lassnig E, et al. Influenza A and B IgG seropositivity and coronary atherosclerosis assessed by angiography. Heart Dis. 2002;4(6):349–54.PubMedCrossRefGoogle Scholar
  14. 14.
    Madjid M, Naghavi M, Litovsky S, Casscells SW. Influenza and cardiovascular disease: a new opportunity for prevention and the need for further studies. Circulation. 2003;108:2730–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Collins SD. Excess mortality from causes other than influenza and pneumonia during influenza epidemics. Public Health Rep. 1932;47:2159–80.CrossRefGoogle Scholar
  16. 16.
    Gross PA, Hermogenes AW, Sacks HS, Lau J, Levandowski RA. The efficacy of influenza vaccine in elderly persons: a meta-analysis and review of the literature. Ann Intern Med. 1995;123(7):518–27.PubMedGoogle Scholar
  17. 17.
    Alpert JS, Thygesen K, Antman E, Bassand JP. Myocardial infarction redefined: a consensus document of the Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of Myocardial Infarction. J Am Coll Cardiol. 2000;36(3):959–69.PubMedCrossRefGoogle Scholar
  18. 18.
    Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. 2003;26:S5–20.CrossRefGoogle Scholar
  19. 19.
    Whitworth JA, World Health Organization. International Society of Hypertension Writing Group. World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension. J Hypertens. 2003;21:1983–92.PubMedCrossRefGoogle Scholar
  20. 20.
    Lai S, Fishman EK, Lai H, Pannu H, Detrick B. Serum IL-6 levels are associated with significant coronary stenosis in cardiovascularly asymptomatic inner-city black adults in the US. Inflamm Res. 2009;58(1):15–21.PubMedCrossRefGoogle Scholar
  21. 21.
    Leon ML, Zuckerman SH. Gamma interferon: a central mediator in atherosclerosis. Inflamm Res. 2005;54(10):395–411.PubMedCrossRefGoogle Scholar
  22. 22.
    Jha HC, Divya A, Prasad J, Mittal A. Plasma circulatory markers in male and female patients with coronary artery disease. Heart Lung. 2010;39(4):296–303.PubMedCrossRefGoogle Scholar
  23. 23.
    Van Lenten BJ, Wagner AC, Nayak DP, Hama S, Navab M, Fogelman AM. C-reactive protein is a mediator of cardiovascular disease. Eur Heart J. 2010;31(17):2087–91.CrossRefGoogle Scholar
  24. 24.
    Rizvi AA. Cytokine biomarkers, endothelial inflammation, and atherosclerosis in the metabolic syndrome: emerging concepts. Am J Med Sci. 2009;338(4):310–8.PubMedCrossRefGoogle Scholar
  25. 25.
    Van Lenten BJ, Wagner AC, Nayak DP, Hama S, Navab M, Fogelman AM. High-density lipoprotein loses its anti-inflammatory properties during acute influenza A infection. Circulation. 2001;103:2283–8.PubMedGoogle Scholar
  26. 26.
    Van Lenten BJ, Wagner AC, Anantharamaiah GM, Garber DW, Fishbein MC, Adhikary L, et al. Influenza infection promotes macrophage traffic into arteries of mice that is prevented by D-4F, an apolipoprotein A-I mimetic peptide. Circulation. 2002;106:1127–32.PubMedCrossRefGoogle Scholar
  27. 27.
    Bouwman JJ, Visseren FL, Bosch MC, Bouter KP, Diepersloot RJ. Procoagulant and inflammatory response of virus-infected monocytes. Eur J Clin Invest. 2002;32(10):759–66.PubMedCrossRefGoogle Scholar
  28. 28.
    Visseren FL, Bouwman JJ, Bouter KP, Diepersloot RJ, de Groot PH, Erkelens DW. Procoagulant activity of endothelial cells after infection with respiratory viruses. Thromb Haemost. 2000;84:319–24.PubMedGoogle Scholar
  29. 29.
    Naghavi M, Wyde P, Litovsky S, Madjid M, Akhtar A, Naguib S, et al. Influenza infection exerts prominent inflammatory and thrombotic effects on the atherosclerotic plaques of apolipoprotein E-deficient mice. Circulation. 2003;107:762–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Nichol KL, Nordin J, Mullooly J, Lask R, Fillbrandt K, Iwane M. Influenza vaccination and reduction in hospitalizations for cardiac disease and stroke among the elderly. N Engl J Med. 2003;348(14):1322–32.PubMedCrossRefGoogle Scholar
  31. 31.
    Loppnow H, Werdan K, Buerke M. Invited review: vascular cells contribute to atherosclerosis by cytokine-and innate-immunity-related inflammatory mechanisms. Innate Immun. 2008;14(2):63–87.PubMedCrossRefGoogle Scholar
  32. 32.
    Kleemann R, Zadelaar S, Kooistra T. Cytokines and atherosclerosis: a comprehensive review of studies in mice. Cardiovasc Res. 2008;79(3):360–76.PubMedCrossRefGoogle Scholar
  33. 33.
    Nakou ES, Liberopoulos EN, Milionis HJ, Elisaf MS. The role of C-reactive protein in atherosclerotic cardiovascular disease: an overview. Curr Vasc Pharmacol. 2008;6(4):258–70.PubMedCrossRefGoogle Scholar
  34. 34.
    Haidari M, Wyde PR, Litovsky S, Vela D, Ali M, Casscells SW, et al. Influenza virus directly infects, inflames, and resides in the arteries of atherosclerotic and normal mice. Atherosclerosis. 2010;208(1):90–6.PubMedCrossRefGoogle Scholar
  35. 35.
    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;105:2143–7.PubMedCrossRefGoogle Scholar
  36. 36.
    Davis MM, Taubert K, Benin AL, Brown DW, Mensah GA, Baddour LM, American Heart Association, American College of Cardiology, et al. Influenza vaccination as secondary prevention for cardiovascular disease: a science advisory from the American Heart Association/American College of Cardiology. Circulation. 2006;114:1549–53.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Basel AG 2012

Authors and Affiliations

  • Xiuru Guan
    • 1
  • Wei Yang
    • 1
  • Xijuan Sun
    • 1
  • Lanfeng Wang
    • 2
  • Benjiang Ma
    • 3
  • Hongyuan Li
    • 4
  • Jin Zhou
    • 5
    Email author
  1. 1.Department of Laboratory DiagnosticsFirst Affiliated Hospital of Harbin Medical UniversityHarbinChina
  2. 2.Cardiovascular DepartmentFirst Affiliated Hospital of Harbin Medical UniversityHarbinChina
  3. 3.Department of Physician Assistant StudiesUniversity of South AlabamaMontgomeryUSA
  4. 4.Epidemiology Department, College of Public HealthHarbin Medical UniversityHarbinChina
  5. 5.Hematology DepartmentThe First Affiliated Hospital of Harbin Medical UniversityHarbinChina

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