Influenza and Cardiovascular Disease: Does Swine-Origin, 2009 H1N1 Flu Virus Represent a Risk Factor, an Acute Trigger, or Both?

ABSTRACT

Influenza infection has become an important focus of both public and medical attention because of high-level perceived clinical and public health effects, enormously amplified by the current and ongoing 2009 H1N1 flu pandemic, sustained by the swine-origin influenza A (H1N1) virus (S-OIV). The current transmission of this virus among humans appears much higher than that traditionally observed with seasonal influenza, raising several outbreaks of febrile respiratory infection ranging in severity from self-limited to severe, even life-threatening disease. Reliable biological and clinical evidence support a significant association between influenza infection and cardiovascular disorders, so that S-IOV might also be regarded as a potential multifaceted bioweapon able to affect the function of the cardiovascular system through a kaleidoscope of humoral, biological, and biochemical mechanisms. In acute coronary ischemic episodes, on one hand, it seems reasonable to consider any acute influenza virus infection as a precipitating factor that is the final event propelling predisposed individuals (e.g., those with preexisting coronary artery disease) over a threshold that precipitates the development of infarction in synergy with other well-known triggers. On the other hand, influenza virus-induced endothelial dysfunction, modification of lipoprotein metabolism, atherosclerotic plaque outgrowth, and inflammation additionally support the role of influenza infection as a strong cardiovascular risk factor. Comprehensive information regarding the 2009 H1N1 infection remains limited, so that it seems unreasonable to draw definitive conclusions. Nevertheless, current recorded mortality data would lead us to conclude that this new virus might represent a sinister threat to humankind, with cardiovascular mortality risk highlighting an additional crucial role for increasing further the alert against this threat. It also seems reasonable to support calls for vaccination against these viruses, both the seasonal and the new S-OIV, because this might represent a feasible strategy for short- and long-term prevention of virus-associated cardiovascular disease.

KEYWORDS

Cardiovascular disease - flue - influenza - myocardial infarction - 2009 H1N1

REFERENCES

• 1 Yen H L, Webster R G. Pandemic influenza as a current threat.  Curr Top Microbiol Immunol. 2009;  333 3-24
• 2 Gatherer D. The 2009 H1N1 influenza outbreak in its historical context.  J Clin Virol. 2009;  45(3) 174-178
• 3 Peiris J S, Poon L L, Guan Y. Emergence of a novel swine-origin influenza A virus (S-OIV) H1N1 virus in humans.  J Clin Virol. 2009;  45(3) 169-173
• 4 Dawood F S, Jain S, Finelli L Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team et al. Emergence of a novel swine-origin influenza A (H1N1) virus in humans.  N Engl J Med. 2009;  360(25) 2605-2615
• 5 Brockwell-Staats C, Webster R G, Webby R J. Diversity of Influenza Viruses in Swine and the Emergence of a Novel Human Pandemic Influenza A (H1N1).  Influenza Other Respi Viruses. 2009;  3 207-213
• 6 Kuiken T, Taubenberger J K. Pathology of human influenza revisited.  Vaccine. 2008;  26(Suppl 4) D59-D66
• 7 Schnitzler S U, Schnitzler P. An update on swine-origin influenza virus A/H1N1: a review.  Virus Genes. 2009;  , October 7 (Epub ahead of print)
• 8 Madsen W. New swine flu feared to be weaponized strain. Online Journal, April 27, 2009. Available at: http://onlinejournal.com/artman/publish/article_4631.shtml Accessed November 6, 2009
• 9 Hauge S H, Dudman S G, Borgen K et al.. Disease caused by the new influenza A(H1N1) virus [in Norwegian].  Tidsskr Nor Laegeforen. 2009;  129(17) 1736-1739
• 10 Scalera N M, Mossad S B. The first pandemic of the 21st century: a review of the 2009 pandemic variant influenza A (H1N1) virus.  Postgrad Med. 2009;  121(5) 43-47
• 11 Centers for Disease Control and Prevention .2009 H1N1 flu (“swine flu”) and you. Available at: http://www.cdc.gov/H1N1flu/qa.htm Accessed November 6, 2009
• 12 U.S. Department of Health & Human Services .Heart disease and the flu. Available at: http://www.flu.gov/individualfamily/healthconditions/heartdisease/index.html Accessed November 6, 2009
• 13 Gurevich V S. Influenza, autoimmunity and atherogenesis.  Autoimmun Rev. 2005;  4(2) 101-105
• 14 Bourne G, Wedgwood J. Heart-disease and influenza.  Lancet. 1959;  1(7085) 1226-1228
• 15 Bainton D, Jones G R, Hole D. Influenza and ischaemic heart disease—a possible trigger for acute myocardial infarction?.  Int J Epidemiol. 1978;  7(3) 231-239
• 16 Pesonen E, Siitonen O. Acute myocardial infarction precipitated by infectious disease.  Am Heart J. 1981;  101(4) 512-513
• 17 Spodick D H, Flessas A P, Johnson M M. 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(4) 481-482
• 18 Vüllers R, Bültmann B, Fischer H, Haferkamp O. Influenza A virus infection, a precipitating factor for the major heart attack (author’s transl) [in German].  MMW Munch Med Wochenschr. 1980;  122(41) 1415-1417
• 19 Tillett H E, Smith J W, Gooch C D. Excess deaths attributable to influenza in England and Wales: age at death and certified cause.  Int J Epidemiol. 1983;  12(3) 344-352
• 20 Thompson W W, Shay D K, Weintraub E et al.. Mortality associated with influenza and respiratory syncytial virus in the United States.  JAMA. 2003;  289(2) 179-186
• 21 Thompson W W, Shay D K, Weintraub E et al.. Influenza-associated hospitalizations in the United States.  JAMA. 2004;  292(11) 1333-1340
• 22 Bondarenko S S, Tumanov F A. The incidence of exacerbations in chronic diseases in patients hospitalized with influenza and para-influenza [in Russian].  Ter Arkh. 1990;  62(11) 39-42
• 23 Bondarenko S S, Tumanov F A. The effect of influenza and para-influenza on the course of ischemic heart disease [in Russian].  Ter Arkh. 1992;  64(3) 81-83
• 24 Clayton T C, Thompson M, Meade T W. Recent respiratory infection and risk of cardiovascular disease: case-control study through a general practice database.  Eur Heart J. 2008;  29(1) 96-103
• 25 Guan X R, Li X, Xin X M et al.. Influenza virus infection and risk of acute myocardial infarction.  Inflammation. 2008;  31(4) 266-272
• 26 Warren-Gash C, Smeeth L, Hayward A C. Influenza as a trigger for acute myocardial infarction or death from cardiovascular disease: a systematic review.  Lancet Infect Dis. 2009;  9(10) 601-610
• 27 Azambuja M I. Connections: can the 20th century coronary heart disease epidemic reveal something about the 1918 influenza lethality?.  Braz J Med Biol Res. 2008;  41(1) 1-4
• 28 Paoletti R, Gotto Jr A M, Hajjar D P. Inflammation in atherosclerosis and implications for therapy.  Circulation. 2004;  109(23, suppl 1) III20-III26
• 29 Mangge H, Hubmann H, Pilz S, Schauenstein K, Renner W, März W. Beyond cholesterol—inflammatory cytokines, the key mediators in atherosclerosis.  Clin Chem Lab Med. 2004;  42(5) 467-474
• 30 Kher N, Marsh J D. Pathobiology of atherosclerosis—a brief review.  Semin Thromb Hemost. 2004;  30(6) 665-672
• 31 Gattone M, Iacoviello L, Colombo M et al.. Chlamydia pneumoniae and cytomegalovirus seropositivity, inflammatory markers, and the risk of myocardial infarction at a young age.  Am Heart J. 2001;  142(4) 633-640
• 32 Pleskov V M, Bannikov A I, Gurevich V S, Pleskova IuV. Influenza viruses and atherosclerosis: the role of atherosclerotic plaques in prolonging the persistent form of influenza infection [in Russian].  Vestn Ross Akad Med Nauk. 2003;  4(4) 10-13
• 33 Gurevich V S, Pleskov V M, Levaia M V, Bannikov A I, Mitrofanova L B, Urazgil’deeva S A. Influenza virus infection in progressing atherosclerosis [in Russian].  Kardiologiia. 2002;  42(7) 21-24
• 34 Madjid M, Naghavi M, Litovsky S, Casscells S W. Influenza and cardiovascular disease: a new opportunity for prevention and the need for further studies.  Circulation. 2003;  108(22) 2730-2736
• 35 Pleskov V M, Bannikov A I, Zatsev IuV. The receptor-mediated endocytosis of influenza viruses and low-density lipoproteins by tissue cells [in Russian].  Vopr Virusol. 1994;  39(3) 121-125
• 36 Marchesi S, Lupattelli G, Lombardini R et al.. Acute inflammatory state during influenza infection and endothelial function.  Atherosclerosis. 2005;  178(2) 345-350
• 37 Goswami B, Tayal D, Gupta N, Mallika V. Paraoxonase: a multifaceted biomolecule.  Clin Chim Acta. 2009;  410(1–2) 1-12
• 38 James R W. A long and winding road: defining the biological role and clinical importance of paraoxonases.  Clin Chem Lab Med. 2006;  44(9) 1052-1059
• 39 Van Lenten B J, Wagner A C, Nayak D P, Hama S, Navab M, Fogelman A M. High-density lipoprotein loses its anti-inflammatory properties during acute influenza A infection.  Circulation. 2001;  103(18) 2283-2288
• 40 Van Lenten B J, Wagner A C, Anantharamaiah G M 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(9) 1127-1132
• 41 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
• 42 Keller T T, van der Meer J J, Teeling P et al.. Selective expansion of influenza A virus-specific T cells in symptomatic human carotid artery atherosclerotic plaques.  Stroke. 2008;  39(1) 174-179
• 43 Barinov V G, Bogomolov B P, Deviatkin A V, Shvedova L P. Hemostatic changes in various clinical courses of influenza [in Russian].  Klin Med (Mosk). 1989;  67(6) 104-107
• 44 Bogomolov B P, Barinov V G, Deviatkin A V et al.. Hemostasis in influenza and acute respiratory viral infections in the middle-aged and elderly [in Russian].  Ter Arkh. 1990;  62(7) 98-102
• 45 Visseren F L, Bouwman J J, Bouter K P, Diepersloot R J, de Groot P H, Erkelens D W. Procoagulant activity of endothelial cells after infection with respiratory viruses.  Thromb Haemost. 2000;  84(2) 319-324
• 46 Bouwman J J, Visseren F L, Bosch M C, Bouter K P, Diepersloot R J. Procoagulant and inflammatory response of virus-infected monocytes.  Eur J Clin Invest. 2002;  32(10) 759-766
• 47 Anisimova IuN, Trushnikova G V. Infectious-toxic shock and disseminated intravascular coagulation in a pregnant woman with influenza.  Arkh Patol. 1994;  56 79-82
• 48 Terada H, Baldini M, Ebbe S, Madoff M A. Interaction of influenza virus with blood platelets.  Blood. 1966;  28(2) 213-228
• 49 Terada H. Studies on platelets and interaction with particular reference to the interaction of influenza virus with blood platelets [in Japanese].  Nippon Ketsueki Gakkai Zasshi. 1969;  32(1) 45-51
• 50 Chernesky M A, Larke R P, Turpie A G. Interaction between viruses and platelets: requirement of haemolytic activity for platelet aggregation induced by paramyxoviruses.  J Gen Virol. 1973;  21(2) 205-213
• 51 Bogomolov B P, Deviatkin A V, Efimov L L, Mitiushina S A. Microcirculation, hemostasis, and hemorheology in influenza and acute respiratory viral infections in patients with hypertension [in Russian].  Ter Arkh. 2001;  73(11) 7-11
• 52 Bogomolov B P, Deviatkin A V. Microcirculation and hemostasis in influenza and acute viral respiratory infections complicated with pneumonia [in Russian].  Ter Arkh. 2002;  74(3) 44-48
• 53 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
• 54 Nichol K L, 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) 1322-1332
• 55 Gurfinkel E P, de la Fuente R L, 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
• 56 Gurfinkel E P, de la Fuente R L. Two-year follow-up of the FLU Vaccination Acute Coronary Syndromes (FLUVACS) Registry.  Tex Heart Inst J. 2004;  31(1) 28-32
• 57 van der Sande M A, van Asten L, Straus S M, Schim van der Loeff M F, Wallinga J, Conyn-van Spaendonck M A. Sudden deaths following influenza vaccination: can this be expected?.  Vaccine. 2008;  26(3) 379-382
• 58 Davis M M, Taubert K, Benin A L et al.. Influenza vaccination as secondary prevention for cardiovascular disease: a science advisory from the American Heart Association/American College of Cardiology.  J Am Coll Cardiol. 2006;  48(7) 1498-1502
• 59 Ciszewski A, Bilinska Z T, Brydak L B et al.. Influenza vaccination in secondary prevention from coronary ischaemic events in coronary artery disease: FLUCAD study.  Eur Heart J. 2008;  29(11) 1350-1358
• 60 Warren-Gash C, Smeeth L, Hayward A C. Influenza as a trigger for acute myocardial infarction or death from cardiovascular disease: a systematic review.  Lancet Infect Dis. 2009;  9(10) 601-610
• 61 Lavallée P, Perchaud V, Gautier-Bertrand M, Grabli D, Amarenco P. Association between influenza vaccination and reduced risk of brain infarction.  Stroke. 2002;  33(2) 513-518
• 62 Grau A J, Fischer B, Barth C, Ling P, Lichy C, Buggle F. Influenza vaccination is associated with a reduced risk of stroke.  Stroke. 2005;  36(7) 1501-1506
• 63 Heffelfinger J D, Heckbert S R, Psaty B M et al.. Influenza vaccination and risk of incident myocardial infarction.  Hum Vaccin. 2006;  2(4) 161-166
• 64 Jackson L A, Yu O, Heckbert S R Vaccine Safety Datalink Study Group et al. Influenza vaccination is not associated with a reduction in the risk of recurrent coronary events.  Am J Epidemiol. 2002;  156(7) 634-640
• 65 Jackson L A, Nelson J C, Benson P et al.. Functional status is a confounder of the association of influenza vaccine and risk of all cause mortality in seniors.  Int J Epidemiol. 2006;  35(2) 345-352
• 66 Madjid M, Lillibridge S, Mirhaji P, Casscells W. Influenza as a bioweapon.  J R Soc Med. 2003;  96(7) 345-346
• 67 Doshi P. Trends in recorded influenza mortality: United States, 1900–2004.  Am J Public Health. 2008;  98(5) 939-945
• 68 Lippi G, Plebani M. Rapid diagnosis of swine-origin influenza A (H1N1) virus (S-OIV): useful or hype?.  Clin Chem Lab Med. 2010;  48(1) 1-5
• 69 Flucount.org. .Swine flu infection data. Available at: http://www.flucount.org/ Accessed November 6, 2009
• 70 Petrosillo N, Di Bella S, Drapeau C M, Grilli E. The novel influenza A (H1N1) virus pandemic: an update.  Ann Thorac Med. 2009;  4(4) 163-172
• 71 Domínguez-Cherit G, Lapinsky S E, Macias A E et al.. Critically Ill patients with 2009 influenza A(H1N1) in Mexico.  JAMA. 2009;  302(17) 1880-1887
• 72 Madjid M, Aboshady I, Awan I, Litovsky S, Casscells S W. Influenza and cardiovascular disease: is there a causal relationship?.  Tex Heart Inst J. 2004;  31(1) 4-13
• 73 Donaldson G C, Keatinge W R. Excess winter mortality: influenza or cold stress? Observational study.  BMJ. 2002;  324(7329) 89-90
• 74 Keatinge W R. Winter mortality and its causes.  Int J Circumpolar Health. 2002;  61(4) 292-299
• 75 Lippi G, Franchini M, Montagnana M, Filippozzi L, Favaloro E J, Guidi G C. Relationship between 24-h air pollution, emergency department admission and diagnosis of acute coronary syndrome.  J Thromb Thrombolysis. 2009;  , June 25 (Epub ahead of print)
• 76 Louie J K, Acosta M, Winter K for the California Pandemic (H1N1) Working Group et al. Factors associated with death or hospitalization due to pandemic 2009 influenza A(H1N1) infection in California.  JAMA. 2009;  302(17) 1896-1902
• 77 Madjid M, Casscells S W. Of birds and men: cardiologists’ role in influenza pandemics.  Lancet. 2004;  364(9442) 1309