More Evidence That Flu Is Linked to Heart Attacks – Medpage Today

Influenza infection was associated with an increased risk of acute myocardial infarction (MI), especially for those without a prior hospitalization for coronary artery disease (CAD), according to a Dutch observational case series study.

The adjusted relative incidence of acute MI in the 1 to 7 days after laboratory-confirmed influenza infection (the risk period) compared with the control period of 1 year before and 51 weeks after the risk period was 6.16 (95% CI 4.11-9.24), reported Patricia Bruijning-Verhagen, MD, PhD, of Utrecht University in the Netherlands, and colleagues in NEJM Evidence.

Notably, among patients without prior hospitalization for CAD, the relative incidence of acute MI was 16.60 (95% CI 10.45-26.37) compared with 1.43 (95% CI 0.53-3.84) for those who had been previously hospitalized for CAD.

"I was not surprised to find that influenza infection increases the short-term risk of acute myocardial infarction," Bruijning-Verhagen told MedPage Today. "What did surprise me was the finding that the risk was most elevated for persons without a history of hospitalization for cardiovascular disease."

She pointed out that the study included influenza infections that were severe enough to require medical attention and testing. "We do not know whether the findings also apply to milder influenza infections," she said.

The finding that ambulatory adults with underlying, undiagnosed CAD were most at risk for acute MI is crucial, wrote C. Raina MacIntyre, MBBS, PhD, of the University of New South Wales Sydney in Randwick, Australia, and colleagues in an accompanying editorial.

"[Influenza] vaccination is low-hanging fruit for people at risk of acute myocardial infarction who have not yet had a first event," they noted. "It is time that we viewed influenza vaccine as a routine preventive measure for ACS [acute coronary syndrome] and for people with CAD risk factors, along with statins, blood pressure control, and smoking cessation."

MacIntyre and colleagues pointed to the recent randomized Influenza Vaccination After Myocardial Infarction trial, which demonstrated that getting a flu shot early after an MI or with high-risk coronary heart disease resulted in a lower risk of a composite of all-cause death, MI, or stent thrombosis, and a lower risk of all-cause death and cardiovascular death, at 12 months compared with placebo.

Observational studies have also reported a protective effect of the flu vaccine, including a meta-analysis that showed a reduction in acute MI of 29% with the shot.

In the current study, there was no national registry data available for influenza vaccines, so it was not possible to compare acute MI incidence among vaccinated versus unvaccinated people.

Infections with other respiratory viruses besides influenza were also associated with an increased relative incidence of acute MI and "may extend to all acute respiratory infections severe enough to qualify for microbiologic testing," Bruijning-Verhagen and authors wrote.

For RSV, the relative incidence of acute MI was 3.38 (95% CI 1.07-10.71), and was 4.06 (95% CI 2.27-7.25) for other respiratory viruses. For those who had upper respiratory symptoms consistent with a viral infection but had a negative virus test result, the relative incidence was 4.56 (95% CI 2.99-6.94).

The study only included data from before the COVID-19 pandemic, but evidence suggests infection with SARS-CoV-2 is likely associated with detrimental effects on cardiovascular health.

Bruijning-Verhagen and colleagues hypothesized that the increased risk of acute MI after acute influenza and other respiratory infections is caused by increased metabolic demand and effects on inflammatory and coagulation pathways that lead to atherosclerotic plaque destabilization and subsequent occlusion.

The authors also speculated that preventive treatment with antihypertensive and antithrombotic medications might mitigate the risk of acute MI after influenza infection, noting that a post-hoc analysis suggested that acute MI risk was elevated in people with influenza who were not taking preventive medications compared with those who were.

However, in a separate editorial, Lori Dodd, PhD, of the National Institute of Allergy and Infectious Diseases, questioned whether the associations between flu and acute MI in the study represent a true causal link, "or point to some other (unadjusted) factor linking the two."

"A possible explanation is the effect of workup bias, a tendency to test and identify preexisting conditions ... among patients with an acute infection who have preexisting risk factors," Dodd wrote, noting that the study also found a significant association between influenza and hospitalization for diabetes, with no clear explanation. "The increased surveillance for other diagnoses would result in estimates of increased risk after influenza," she posited.

This observational, registry-based study used a self-controlled case series design and included adults ages 35 and older who were tested for respiratory viruses from January 2008 through December 2019. The researchers identified 158,777 PCR tests for influenza from 16 laboratories across the Netherlands and data were linked to national medication, hospitalization, mortality, and administrative databases. Of the PCR tests, 23,405 were positive for influenza and represented unique illness episodes.

A total of 401 episodes were identified with acute MI occurring 1 year before and 1 year after confirmed influenza infection and were included in analysis; 25 cases occurred 1 to 7 days after influenza infection, and the remaining cases occurred during the control period. Over 60% of influenza infections were due to influenza type A.

The median age of the study population was 74 years, 64% were men, and 64% had been previously hospitalized with CAD. Within a year after being infected with influenza, 35% had died (all causes).

Katherine Kahn is a staff writer at MedPage Today, covering the infectious diseases beat. She has been a medical writer for over 15 years.

Disclosures

The study was funded by the Dutch Research Council.

Bruijning-Verhagen reported no conflicts of interest; one co-author received an honorarium and travel fees from Sanofi.

MacIntyre has received funding from Sanofi.

Dodd reported no conflicts of interest.

Primary Source

NEJM Evidence

Source Reference: de Boer AR, et al "Influenza infection and acute myocardial infarction" NEJM Evid 2024; DOI: 10.1056/EVIDoa2300361.

Secondary Source

NEJM Evidence

Source Reference: MacIntyre CR, et al "Influenza vaccine -- low-hanging fruit for prevention of myocardial infarction" NEJM Evid 2024; DOI: 10.1056/EVIDe2400178.

Additional Source

NEJM Evidence

Source Reference: Dodd LE "Influenza and acute myocardial infarction -- causal link or spurious association?" NEJM Evid 2024; DOI: 10.1056/EVIDe2400175.

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More Evidence That Flu Is Linked to Heart Attacks - Medpage Today