Increased risk of acute MI after influenza virus infection
In a Dutch self-controlled case series study, there was a 6-fold higher incidence of acute MI in the first week after influenza virus infection compared with 1 year before and 1 year after, especially in individuals with no prior hospitalization for coronary artery disease.
This summary is based on the publication of De Boer AR, Riezebos-Brilman A, van Hout D, et al. - Influenza Infection and Acute Myocardial Infarction. NEJM Evid. 2024 Jul;3(7):EVIDoa2300361. doi: 10.1056/EVIDoa2300361
Introduction and methods
Background
After influenza, the risk of acute MI (AMI) temporarily increases by 6-fold [1-4]. Additional evidence on the influenza-related risk of CV events is important for prevention policies, particularly to guide a more individualized approach in patients with CV comorbidities.
Aim of the study
The study aim was to further quantify the association between laboratory-confirmed influenza virus infection and the occurrence of AMI, particularly in individuals with and with no known coronary artery disease (CAD).
Methods
In an observational, registry-based, self-controlled case series study, data were collected from individuals aged ≥35 years who were tested for ≥1 respiratory viruses (including influenza virus) in the period January 2008–December 2019 and had an AMI during the 1 year before and 1 year after the date of testing. The self-controlled case series method includes only cases to estimate the relative incidence, and individuals act as their own control (self-controlled). This epidemiological study design corrects for time-invariant but not time-varying confounders.
Laboratory records on respiratory virus polymerase chain reaction (PCR) testing from 16 laboratories across the Netherlands were linked at the individual level to the Dutch Population Registry (containing demographic information), National Cause of Death Registry, Dutch Hospital Discharge Registry, and medication registry. Laboratory-confirmed influenza virus infection was defined as a registered positive PCR test result for influenza virus, and AMI was defined as a registered diagnostic code for either AMI hospitalization or death.
Outcome
The relative incidence of AMI during the risk period (1–7 days after laboratory-confirmed influenza virus infection) was compared with that during the control period (from 52 weeks before through 51 weeks after the risk period).
Main results
- Of the 158,777 PCR tests performed in the study population, 26,221 were positive for influenza virus, constituting 23,405 unique influenza episodes.
- During the observation period of 1 year before until 1 year after the positive PCR test result, a total of 406 AMI events occurred in 401 individuals.
- There were 25 AMI events during the risk period and 394 during the control period. The relative incidence of AMI in the risk period compared with the control period was 6.16 (95%CI: 4.11–9.24).
- Subgroup analyses showed that the relative incidence of AMI was lower in the risk period versus control period in individuals who had been previously hospitalized for CAD (1.43; 95%CI: 0.53–3.84) than those with no prior hospitalization for CAD (16.60; 95%CI: 10.45–26.37).
- In exploratory post-hoc analyses, the use of antithrombotic medication was associated with a lower relative incidence of AMI compared with nonuse (4.10; 95%CI: 2.35–7.14 vs. 13.50; 95%CI: 7.39–24.70), as was the use of preventive CV medication (e.g., antihypertensives, antithrombotic medication) compared with nonuse (4.99; 95%CI: 3.11–8.03 vs. 16.13; 95%CI: 7.25–35.91).
- Sensitivity analyses controlled for, for example, calendar month or including only first AMI events showed similar results.
Conclusion
In this Dutch, observational, self-controlled case series study, influenza virus infection was associated with a 6-fold higher incidence of AMI in the first week after the infection compared with the control period (i.e., from 52 weeks before through 51 weeks after risk period). Individuals with no prior hospitalization for CAD had an even higher relative incidence of AMI (10-fold increased) compared with those previously hospitalized for CAD.
Individuals who did not take antithrombotic medication or preventive CV medication also had an elevated AMI risk after influenza virus infection compared with those taking either medication. According to the authors, this indicates “a potential role for primary and secondary prevention measures in patients with influenza, even [in those with no] established cardiovascular risk.”
References
1. Kwong JC, Schwartz KL, Campitelli MA, et al. Acute myocardial infarction after laboratory-confirmed influenza infection. N Engl J Med 2018;378:345-353. DOI: 10.1056/NEJMoa1702090.
2. Young-Xu Y, Smith J, Mahmud SM, et al. Laboratory-confirmed influenza infection and acute myocardial infarction among United States senior Veterans. PLoS One 2020;15:e0243248. DOI: 10.1371/journal.pone.0243248.
3. Ohland J, Warren-Gash C, Blackburn R, et al. Acute myocardial infarctions and stroke triggered by laboratory-confirmed respiratory infections in Denmark, 2010 to 2016. Euro Surveill 2020;25:1900199. DOI: 10.2807/1560-7917.ES.2020.25.17.1900199.
4. 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;51:1701794. DOI: 10.1183/13993003.01794-2017.