Flu can trigger a fatal heart attack

Coming down with influenza – commonly called flu – can increase the risk of having a heart attack by sixfold. This is the takeaway from a replication study presented at ECCMID 2023.

Individuals who are diagnosed with flu were 6.16 times more likely to experience a heart attack – otherwise known as acute myocardial infarction (MI) – within the week after a flu infection compared with the year before or after the infection. [ECCMID 2023, abstract O1127]

“This is an interesting finding, with important implications,” said study author Dr Annemarijn De Boer of the Julius Center for Life Sciences and Primary Care, UMC Utrecht, Utrecht, the Netherlands.

 

Strong supportive evidence linking serologically confirmed influenza with acute MI in the first year after infection came from a prospective, multicentre, self-controlled case-series study from Canada, showing a 6-fold higher risk for acute MI (relative risk [RR], 6.05, 95 percent confidence interval [CI], 3.86–9.50; p<0.05) during the first 7 days of influenza infection (risk interval), compared with 52 weeks before and 51 weeks after the risk interval. [N Engl J Med 2018; 378:345-353]

The pathophysiology behind the link between acute MI and influenza rests on the release of inflammation cytokine and rupture of atherosclerotic plaque, triggering prothrombotic events leading to coronary artery occlusion. [Eur Heart J Suppl 2020;22(Suppl E):E68-E72]

However, the Canadian study did not include mortality data which De Boer said is essential to account for censoring and capture out-of-hospital deaths related to acute MI.

Validating results of previous research

This prompted De Boer and her colleagues to conduct a replication study using a different cohort of patients from the Netherlands. Laboratory records of polymerase chain reaction (PCR) testing for respiratory viruses from 16 laboratories across the country, covering 40 percent of the population, were linked to national mortality, hospitalization, and administrative registries, and analysed.

Influenza infection was defined as a positive PCR-test, whereas acute MI as either a hospitalization or death registered as ICD-10 code I21.

Influenza infections during acute MI hospitalization were excluded as no temporal relation could be established. Using a self-controlled case-series design, the researchers compared acute MI incidence during the risk interval with the control interval period.

There were 26,221 cases of flu recorded between 2008 and 2019. Of this number, 401 individuals had at least one episode of acute MI within the year before or after their flu diagnosis, for a total of 419 incidents of heart attacks – 25 occurred in the first 7 days after a flu diagnosis, 217 within a year before the diagnosis, and 177 a year after the diagnosis (the first 7 days were excluded).

Around a third of the patients (139/401) died from any cause within a year after flu infection. Excluding data from death records, as in the Canadian study, reduced the incidence of heart attack to 2.42-fold in the first week.

“Clearly, there was a significant – albeit weaker – association between flu and acute MI in our study,” De Boer told delegates attending ECCMID 2023. “Compared with the original Canadian study, the differences in results may be explained by differences in testing practices and organization of care, including limited influenza virus testing outside hospital setting.”

She clarified that in the Netherlands, testing for flu in out-of-hospital settings is less common than in Canada. However, the association observed in the study remained significant. “By using a similar methodology with that of the original Canadian study, we were able to confirm the generalizability of myocardial risk from influenza infection in different populations.”

What the replication study tells us

Flu is caused by infection with influenza viruses and is highly contagious. Most people with flu recover in a few days, but some develop complications (sinus and ear infections or pneumonia, which at times, can be fatal). Although flu vaccination is not 100 percent effective, it reduces the chances of having severe complications from the infection – reason why the US Centers for Disease Control and Prevention recommends yearly flu shots for people aged 6 months and older who do not have contraindications.

Acute MI on its own is a life-threatening condition resulting from the cessation of blood flow to the heart muscle, causing tissue damage.

“With the potential public health implications of the association between influenza and acute heart attacks, showing robustness of results in a different study population is important,” De Boer pointed out.

“Our findings endorse strategies to prevent influenza infection, including vaccination. We also advocate heightened awareness among physicians and their patients hospitalized with flu for symptoms of heart attack,” she added.

While it was not clear from their findings whether those with less severe flu are also at risk for acute MI, De Boer said it is prudent for both patients and clinicians to be aware of the link.