Research Open Access
Like 0



Several studies have investigated a possible association between respiratory infection and acute myocardial infarction (MI). As both influenza and pneumococcal infections are vaccine preventable, understanding the populations affected by virus-induced cardiovascular complications is important to guide public health and clinical practice.


This observational study aimed to quantify the association between laboratory-confirmed respiratory bacteria or virus infections and risk of first MI or stroke, by using self-controlled case series (SCCS) analysis of anonymised linked electronic Danish health records.


The SCCS method was used to determine the relative incidence of the first event of MI and stroke occurring within 28 days after laboratory-confirmed respiratory infections compared with the baseline time period.


In the age and season adjusted analyses for first acute MI, the incidence ratios (IR) of a MI event occurring during the risk period were significantly elevated following a infection with values of 20.1, 11.0 and 4.9 during 1–3, 4–7 and 8–14 days, respectively and following respiratory virus infection with values of 15.2, 4.5 and 4.4 during 1–3, 8–14 and 15–28 days, respectively. The significantly elevated IRs for stroke following an infection were 25.5 and 6.3 during 1–3 and 8–14 days, respectively and following respiratory virus infection 8.3, 7.8 and 6.2 during 1–3, 4–7 and 8–14 days, respectively.


This study suggested a significant cardiovascular event triggering effect following infection with and respiratory viruses (mainly influenza), indicating the importance of protection against vaccine-preventable respiratory infections.


Article metrics loading...

Loading full text...

Full text loading...



  1. World Health Organization (WHO). The top 10 causes of death. Geneva: WHO; 2018. [Accessed 26 Nov 2018]. Available from: www.who.int/mediacentre/factsheets/fs310/en/index.html
  2. Collins SD. Excess Mortality from Causes Other than Influenza and Pneumonia during Influenza Epidemics. Public Health Rep. 1932;47(46):2159-79.  https://doi.org/10.2307/4580606  PMID: 19315373 
  3. Warren-Gash C, Smeeth L, Hayward AC. Influenza as a trigger for acute myocardial infarction or death from cardiovascular disease: a systematic review. Lancet Infect Dis. 2009;9(10):601-10.  https://doi.org/10.1016/S1473-3099(09)70233-6  PMID: 19778762 
  4. Barnes M, Heywood AE, Mahimbo A, Rahman B, Newall AT, Macintyre CR. Acute myocardial infarction and influenza: a meta-analysis of case-control studies. Heart. 2015;101(21):1738-47.  https://doi.org/10.1136/heartjnl-2015-307691  PMID: 26310262 
  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(26):345-53.  https://doi.org/10.1056/NEJMoa1702090  PMID: 29949484 
  6. Blackburn R, Zhao H, Pebody R, Hayward A, Warren-Gash C. Laboratory-Confirmed Respiratory Infections as Predictors of Hospital Admission for Myocardial Infarction and Stroke: Time-Series Analysis of English Data for 2004-2015. Clin Infect Dis. 2018;67(1):8-17.  https://doi.org/10.1093/cid/cix1144  PMID: 29324996 
  7. 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 
  8. Corrales-Medina VF, Suh KN, Rose G, Chirinos JA, Doucette S, Cameron DW, et al. Cardiac complications in patients with community-acquired pneumonia: a systematic review and meta-analysis of observational studies. PLoS Med. 2011;8(6):e1001048.  https://doi.org/10.1371/journal.pmed.1001048  PMID: 21738449 
  9. Mazur NI, Higgins D, Nunes MC, Melero JA, Langedijk AC, Horsley N, et al. , Respiratory Syncytial Virus Network (ReSViNET) Foundation. The respiratory syncytial virus vaccine landscape: lessons from the graveyard and promising candidates. Lancet Infect Dis. 2018;18(10):e295-311.  https://doi.org/10.1016/S1473-3099(18)30292-5  PMID: 29914800 
  10. Voldstedlund M, Haarh M, Mølbak K, MiBa Board of Representatives. The Danish Microbiology Database (MiBa) 2010 to 2013. Euro Surveill. 2014;19(1):20667.  https://doi.org/10.2807/1560-7917.ES2014.19.1.20667  PMID: 24434175 
  11. Whitaker HJ, Farrington CP, Spiessens B, Musonda P. Tutorial in biostatistics: the self-controlled case series method. Stat Med. 2006;25(10):1768-97.  https://doi.org/10.1002/sim.2302  PMID: 16220518 
  12. 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 
  13. Andersen TF, Madsen M, Jørgensen J, Mellemkjoer L, Olsen JH. The Danish National Hospital Register. A valuable source of data for modern health sciences. Dan Med Bull. 1999;46(3):263-8. PMID: 10421985 
  14. World Health Organization (WHO). International Statistical Classification of Diseases and Health-related Problems, 10th Revision. Geneva: WHO; 2016. Available from: http://apps.who.int/classifications/icd10/browse/2016/en
  15. SAS. SAS. Cary, NC, USA: SAS Institute.
  16. StataCorp. Stata Statistical Software. College Station, TX: StataCorp LP.
  17. Trebbien R, Fischer TK, Krause TG, Nielsen L, Nielsen XC, Weinreich LS, et al. Changes in genetically drifted H3N2 influenza A viruses and vaccine effectiveness in adults 65 years and older during the 2016/17 season in Denmark. J Clin Virol. 2017;94:1-7.  https://doi.org/10.1016/j.jcv.2017.06.007  PMID: 28697450 
  18. Kantsø B, Jørgensen CS, Slotved HC, Hoffman S, Suppli CH, Valentiner-Branth P. Forslag til pneumokokvaccination uden for børnevaccinationsprogrammet. [Suggestions for pneumococcal vaccination outside the childhood vaccination programme]. Copenhagen: Statens Serum Institut; 2014.
  19. Kantsø B. Pneumokokvaccination uden for børnevaccinationsprogrammet i Danmark. [Pneumococcal vaccination outside the childhood vaccination programme in Denmark]. Report No.: Version 1.3. Copenhagen: Statens Serum Institut; 2014. p. 1-30.
  20. Harboe ZB, Benfield TL, Valentiner-Branth P, Hjuler T, Lambertsen L, Kaltoft M, et al. Temporal trends in invasive pneumococcal disease and pneumococcal serotypes over 7 decades. Clin Infect Dis. 2010;50(3):329-37.  https://doi.org/10.1086/649872  PMID: 20047478 
  21. Kyaw MH, Rose CE Jr, Fry AM, Singleton JA, Moore Z, Zell ER, et al. , Active Bacterial Core Surveillance Program of the Emerging Infections Program Network. The influence of chronic illnesses on the incidence of invasive pneumococcal disease in adults. J Infect Dis. 2005;192(3):377-86.  https://doi.org/10.1086/431521  PMID: 15995950 
  22. van Hoek AJ, Andrews N, Waight PA, Stowe J, Gates P, George R, et al. The effect of underlying clinical conditions on the risk of developing invasive pneumococcal disease in England. J Infect. 2012;65(1):17-24.  https://doi.org/10.1016/j.jinf.2012.02.017  PMID: 22394683 
  23. 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 
  24. Krarup L-H, Boysen G, Janjua H, Prescott E, Truelsen T. Validity of stroke diagnoses in a National Register of Patients. Neuroepidemiology. 2007;28(3):150-4.  https://doi.org/10.1159/000102143  PMID: 17478969 
  25. Johnsen SP, Overvad K, Sørensen HT, Tjønneland A, Husted SE. Predictive value of stroke and transient ischemic attack discharge diagnoses in The Danish National Registry of Patients. J Clin Epidemiol. 2002;55(6):602-7.  https://doi.org/10.1016/S0895-4356(02)00391-8  PMID: 12063102 

Data & Media loading...

Submit comment
Comment moderation successfully completed
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error