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2025 theme: Vaccines

Abstract

BACKGROUND

Influenza infection is a recognised trigger of acute myocardial infarction (AMI) and stroke, but whether influenza vaccination modifies this risk remains unclear.

AIM

We aimed to quantify the short-term cardiovascular risk after laboratory-confirmed influenza infection and assess whether vaccination attenuates it.

METHODS

We conducted a nationwide self-controlled case series study using Danish health registries (2014–2025) and included individuals aged ≥ 40 years with a first-ever hospital admission for AMI or stroke within ± 365 days of a PCR-confirmed influenza infection. We defined days 1–7 after specimen date as the risk period and excluded a 14-day pre-exposure period to reduce reverse causality, where influenza testing might be prompted by cardiovascular disease symptoms. We linked testing, hospitalisation, vaccination and mortality data deterministically via unique personal identifiers. We estimated incidence rate ratios (IRRs) and 95% confidence intervals (CI) with conditional Poisson regression.

RESULTS

Among 1,221 individuals with a first-ever AMI (n = 429; 35%) or stroke (n = 792; 65%), median age was 75 years (interquartile range: 66–82); 561 (46%) were female. After calendar-month adjustment, the IRR for cardiovascular events during the risk period was 3.5 (95% CI: 2.6–4.7), higher for AMI (IRR = 4.7; 95% CI: 3.1–7.4) than stroke (IRR = 2.9; 95% CI: 2.0–4.2). Prior influenza vaccination during the same influenza season, recorded in 610 (50%) episodes, reduced the excess risk of AMI or stroke associated with influenza infection (interaction p = 0.020).

CONCLUSIONS

Influenza infection conferred a transiently increased risk of first-time AMI and stroke. Vaccination substantially attenuated this risk, supporting its role in preventing cardiovascular complications after breakthrough infection.

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This work is licensed under a Creative Commons Attribution 4.0 International License.
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2026-04-02
2026-04-13
/content/10.2807/1560-7917.ES.2026.31.13.2500706
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References

  1. Mensah GA, Fuster V, Murray CJL, Roth GA, Global Burden of Cardiovascular Diseases and Risks Collaborators. Global burden of cardiovascular diseases and risks, 1990-2022. J Am Coll Cardiol. 2023;82(25):2350-473.  https://doi.org/10.1016/j.jacc.2023.11.007  PMID: 38092509 
  2. Luengo-Fernandez R, Walli-Attaei M, Gray A, Torbica A, Maggioni AP, Huculeci R, et al. Economic burden of cardiovascular diseases in the European Union: a population-based cost study. Eur Heart J. 2023;44(45):4752-67.  https://doi.org/10.1093/eurheartj/ehad583  PMID: 37632363 
  3. Muscente F, De Caterina R. Causal relationship between influenza infection and risk of acute myocardial infarction: pathophysiological hypothesis and clinical implications. Eur Heart J Suppl. 2020;22(Suppl E):E68-72.  https://doi.org/10.1093/eurheartj/suaa064  PMID: 32523443 
  4. Petersen I, Douglas I, Whitaker H. Self controlled case series methods: an alternative to standard epidemiological study designs. BMJ. 2016;354:i4515.  https://doi.org/10.1136/bmj.i4515  PMID: 27618829 
  5. Kwong JC, Schwartz KL, Campitelli MA, Chung H, Crowcroft NS, Karnauchow T, et al. Acute myocardial infarction after laboratory-confirmed influenza infection. N Engl J Med. 2018;378(4):345-53.  https://doi.org/10.1056/NEJMoa1702090  PMID: 29365305 
  6. Muñoz-Quiles C, López-Lacort M, Urchueguía A, Díez-Domingo J, Orrico-Sánchez A. Risk of cardiovascular events after influenza: a population-based self-controlled case series study, Spain, 2011-2018. J Infect Dis. 2024;230(3):e722-31.  https://doi.org/10.1093/infdis/jiae070  PMID: 38330324 
  7. de Boer AR, Riezebos-Brilman A, van Hout D, et al. Influenza infection and acute myocardial infarction. NEJM Evid. 2024;3:EVIDoa2300361.
  8. Warren-Gash C, Blackburn R, Whitaker H, McMenamin J, Hayward AC. Laboratory-confirmed respiratory infections as triggers for acute myocardial infarction and stroke: a self-controlled case series analysis of national linked datasets from Scotland. Eur Respir J. 2018;51(3):1701794.  https://doi.org/10.1183/13993003.01794-2017  PMID: 29563170 
  9. Ohland J, Warren-Gash C, Blackburn R, Mølbak K, Valentiner-Branth P, Nielsen J, et al. Acute myocardial infarctions and stroke triggered by laboratory-confirmed respiratory infections in Denmark, 2010 to 2016. Euro Surveill. 2020;25(17):1900199.  https://doi.org/10.2807/1560-7917.ES.2020.25.17.1900199  PMID: 32372757 
  10. Behrouzi B, Bhatt DL, Cannon CP, Vardeny O, Lee DS, Solomon SD, et al. Association of influenza vaccination with cardiovascular risk: a meta-analysis. JAMA Netw Open. 2022;5(4):e228873.  https://doi.org/10.1001/jamanetworkopen.2022.8873  PMID: 35486404 
  11. Smeeth L, Thomas SL, Hall AJ, Hubbard R, Farrington P, Vallance P. Risk of myocardial infarction and stroke after acute infection or vaccination. N Engl J Med. 2004;351(25):2611-8.  https://doi.org/10.1056/NEJMoa041747  PMID: 15602021 
  12. Gwini SM, Coupland CAC, Siriwardena AN. The effect of influenza vaccination on risk of acute myocardial infarction: self-controlled case-series study. Vaccine. 2011;29(6):1145-9.  https://doi.org/10.1016/j.vaccine.2010.12.017  PMID: 21172383 
  13. Caldeira D, Rodrigues B, David C, Costa J, Pinto FJ, Ferreira JJ. The association of influenza infection and vaccine with myocardial infarction: systematic review and meta-analysis of self-controlled case series. Expert Rev Vaccines. 2019;18(11):1211-7.  https://doi.org/10.1080/14760584.2019.1690459  PMID: 31693865 
  14. World Health Organization. Vaccines against influenza: WHO position paper – May 2022. Wkly Epidemiol Rec. 2022;97:185-208.
  15. Brennan AC, Campbell RT, Lee MMY. Influenza vaccination: Simple, safe, and effective for patients with ischaemic heart disease and heart failure. Eur J Heart Fail. 2023;25(9):1693-5.  https://doi.org/10.1002/ejhf.2993  PMID: 37581224 
  16. European Centre for Disease Prevention and Control (ECDC). Survey report on national seasonal influenza vaccination recommendations and coverage rates in EU/EEA countries. Stockholm: ECDC; 2024. Available from: https://www.ecdc.europa.eu/sites/default/files/documents/Seasonalflu%20vacc%20coverage%20and%20recommendations%20-%2026%20Nov.pdf
  17. Statens Serum Institut (SSI). Influenzavaccination. [Influenza vaccination]. Copenhagen: SSI. [Accessed: 2 May 2025]. Danish. Available from: https://www.ssi.dk/vaccinationer/influenzavaccination
  18. Sundbøll J, Adelborg K, Munch T, Frøslev T, Sørensen HT, Bøtker HE, et al. Positive predictive value of cardiovascular diagnoses in the Danish National Patient Registry: a validation study. BMJ Open. 2016;6(11):e012832.  https://doi.org/10.1136/bmjopen-2016-012832  PMID: 27864249 
  19. Lühdorf P, Overvad K, Schmidt EB, Johnsen SP, Bach FW. Predictive value of stroke discharge diagnoses in the Danish National Patient Register. Scand J Public Health. 2017;45(6):630-6.  https://doi.org/10.1177/1403494817716582  PMID: 28701076 
  20. Det Centrale Personregister (CPR). Juridisk kønsskifte (transkønnede). [Legal gender reassignment (transgender people)]. Copenhagen: CPR. [Accessed: 18 Mar 2026]. Danish. Available from: https://www.cpr.dk/borgere/kan-jeg-faa-et-nyt-personnummer/juridisk-koensskifte-transkoennede
  21. Heidari S, Babor TF, De Castro P, Tort S, Curno M. Sex and Gender Equity in Research: rationale for the SAGER guidelines and recommended use. Res Integr Peer Rev. 2016;1(1):2.  https://doi.org/10.1186/s41073-016-0007-6  PMID: 29451543 
  22. Guan X, Yang W, Sun X, Wang L, Ma B, Li H, et al. Association of influenza virus infection and inflammatory cytokines with acute myocardial infarction. Inflamm Res. 2012;61(6):591-8.  https://doi.org/10.1007/s00011-012-0449-3  PMID: 22373653 
  23. Cheng HY, Fung E, Choi KC, Zou HJ, Chair SY. Early risk of acute myocardial infarction following hospitalization for severe influenza infection in the middle-aged population of Hong Kong. PLoS One. 2022;17(8):e0272661.  https://doi.org/10.1371/journal.pone.0272661  PMID: 35944002 
  24. Nguyen TQ, Vlasenko D, Shetty AN, Zhao E, Reid CM, Clothier HJ, et al. Systematic review and meta-analysis of respiratory viral triggers for acute myocardial infarction and stroke. Cardiovasc Res. 2025;121(9):1330-44.  https://doi.org/10.1093/cvr/cvaf092  PMID: 40570137 
  25. Korves C, Neupane N, Smith J, Young-Xu Y, van Aalst R, Mahmud SM, et al. Coronary and cerebrovascular events and exacerbation of existing conditions after PCR-confirmed influenza infection among US veterans: a self-controlled case series study. Influenza Other Respir Viruses. 2024;18(6):e13304.  https://doi.org/10.1111/irv.13304  PMID: 38845386 
  26. Panikkath R, Costilla V, Hoang P, Wood J, Gruden JF, Dietrich B, et al. Chest pain and diarrhea: a case of Campylobacter jejuni-associated myocarditis. J Emerg Med. 2014;46(2):180-3.  https://doi.org/10.1016/j.jemermed.2013.08.060  PMID: 24188611 
  27. Johansen ND, Modin D, Pardo-Seco J, Rodriguez-Tenreiro-Sánchez C, Loiacono MM, Harris RC, et al. Effectiveness of high-dose influenza vaccine against hospitalisations in older adults (FLUNITY-HD): an individual-level pooled analysis. Lancet. 2025;406(10518):2425-34.  https://doi.org/10.1016/S0140-6736(25)01742-8  PMID: 41115437 
Influenza vaccination attenuates acute myocardial infarction and stroke risk following influenza infection: a register-based, self-controlled case series study, Denmark, 2014 to 2025
<p class="citation"> <span>Citation style for this article:</span> <span class="meta-value authors"> <a href="/search?value1=Roberto+Croci&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Croci Roberto</a>, <a href="/search?value1=Johanna+J+Young&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Young Johanna J</a>, <a href="/search?value1=Hanne-Dorthe+Emborg&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Emborg Hanne-Dorthe</a>, <a href="/search?value1=Palle+Valentiner-Branth&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Valentiner-Branth Palle</a>, <a href="/search?value1=Steen+Ethelberg&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Ethelberg Steen</a>, <a href="/search?value1=Christian+Holm+Hansen&option1=author&noRedirect=true" class="nonDisambigAuthorLink">Hansen Christian Holm</a></span>. Influenza vaccination attenuates acute myocardial infarction and stroke risk following influenza infection: a register-based, self-controlled case series study, Denmark, 2014 to 2025. <a href="/content/ecdc">Euro Surveill.</a> 2026;31(13):pii=2500706. <a href="https://doi.org/10.2807/1560-7917.ES.2026.31.13.2500706" title="doi link" target="_blank">https://doi.org/10.2807/1560-7917.ES.2026.31.13.2500706</a> <span class="ES_Article_citation"> <span class="generated">Received</span>: 10 Sept 2025;&nbsp;&nbsp; <span class="generated">Accepted</span>: 11 Dec 2025 </span> </p>
/content/10.2807/1560-7917.ES.2026.31.13.2500706
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