Influenza Vaccination May Guard Against Heart Attack and Stroke—Even After Breakthrough Infection

Getting vaccinated against influenza may offer a layer of cardiovascular protection that goes well beyond simply avoiding the flu itself, including in patients who still get infected after vaccination, according to findings from a landmark new study published in Eurosurveillance.¹

The findings carry meaningful implications for pharmacists, who are often the most accessible health care professionals for high-risk patients during flu season and are uniquely positioned to reinforce vaccination counseling for those with cardiovascular disease.

A Closer Look at the Study

Researchers from Statens Serum Institut in Copenhagen, Denmark, conducted a register-based, self-controlled case series study drawing on Danish health registry data spanning 9 consecutive influenza seasons from 2014 to 2025. The study enrolled 1221 adults 40 years and older who experienced a first-ever hospitalization for acute myocardial infarction (AMI) or stroke within approximately 1 year of a laboratory-confirmed influenza infection. Among the cohort, which included 660 men and 561 women with a median age of about 75 years, 65% were hospitalized for stroke and 35% for AMI.¹

Using conditional Poisson regression and a self-controlled case series design, which compares event timing within the same individual to control for fixed confounders such as comorbidities and socioeconomic status, the team found that the risk of a first-time hospitalization for AMI or stroke during the first week after a positive influenza test was dramatically elevated compared with all other time periods. Specifically, heart attack risk increased 5-fold and stroke risk tripled in that acute window.¹

Critically, among the 1231 polymerase chain reaction–confirmed influenza infections analyzed, approximately half occurred in patients who had already received that season’s flu vaccine. Yet vaccination was associated with roughly half the cardiovascular risk compared with unvaccinated individuals who were infected, suggesting the vaccine provides meaningful protection against serious cardiac events even when it fails to prevent infection altogether.¹

Why Influenza Is a Cardiovascular Trigger

The biological plausibility for this relationship is well established. Influenza infection triggers a cascade of systemic inflammatory responses, including the release of proinflammatory cytokines such as IL-6 and tumor necrosis factor-α, which can destabilize preexisting atherosclerotic plaques and promote thrombosis. The virus also causes endothelial dysfunction, increases plasma viscosity, increases adrenergic activity, and creates a prothrombotic state that elevates thromboembolic risk in proportion to disease severity. Together, these mechanisms create conditions that can precipitate both type 1 myocardial infarction (MI), driven by plaque rupture, and type 2 MI, driven by a mismatch between oxygen supply and demand.^2-4

The cardiovascular consequences of influenza are not a new concern. The CDC notes that among adults hospitalized with flu in recent seasons, heart disease was one of the most common underlying conditions, with roughly half of hospitalized patients with flu carrying a cardiac diagnosis. Data from a 2018 study cited by the CDC showed that the risk of heart attack was 6 times higher in the week following a confirmed flu infection.⁵

Prior Evidence on Vaccination and Cardiovascular Outcomes

The Danish study builds on a growing body of research linking influenza vaccination to reduced cardiovascular morbidity. In a 2023 meta-analysis, whose findings were published in Scientific Reports, investigators analyzed 9059 patients across multiple randomized controlled trials and found that vaccinated individuals had a 30% lower risk of major cardiovascular events than placebo recipients (risk ratio [RR], 0.70; 95% CI, 0.55-0.91), with cardiovascular mortality reduced by approximately 33%. Data from a separate meta-analysis published in the Journal of the American Heart Association revealed that influenza vaccination was associated with a 25% reduction in all-cause mortality—a reduction comparable in magnitude to guideline-directed therapies such as β-blockers and angiotensin-converting enzyme inhibitors.^6,7

Implications for Pharmacy Practice

The dual-protection finding is particularly significant for pharmacists. Patients with existing cardiovascular disease or risk factors are precisely the population most likely to present at the pharmacy counter for flu shots and most likely to benefit from them on multiple fronts. As the authors of the Eurosurveillance study note, highlighting the vaccine's protection against both infection and its cardiovascular complications “could have a substantial public health impact” and may strengthen the economic case for influenza vaccination programs.¹

Pharmacists should ensure conversations with at-risk patients emphasize not only infection prevention but also the added layer of cardiovascular risk reduction, even with patients who may be skeptical of vaccine efficacy. The study’s authors note that if these findings are confirmed in additional settings, they would support refining vaccination recommendations across Europe and, by extension, globally.¹

Study Limitations

The study did not account for differences in vaccine effectiveness across seasons, which can vary based on strain match, nor could it assess whether vaccination timing or sex-specific factors influenced outcomes. Results may also not be fully generalizable to populations with different influenza epidemiology or health care systems.¹

REFERENCES

1. Croci R, Young JJ, Emborg HD, Valentiner-Branth P, Ethelberg S, Hansen CH. Influenza vaccination attenuates acute myocardial infarction and stroke risk following influenza infection: a register-based, self-controlled case series study, Denmark, 2014 to 2025. Eurosurveillance. 2026;31(13):pii=2500706. doi:10.2807/1560-7917.ES.2026.31.13.2500706

2. Mohammadi M, Kianifard N, Fazlzadeh A, et al. Association between influenza infection and cardiovascular diseases: a systematic review and meta-analysis. JRSM Cardiovasc Dis. 2025;14:20480040251407014. doi:10.1177/20480040251407014

3. Skaarup KG, Modin D, Nielsen L, Jensen JUS, Biering-Sørensen T. Influenza and cardiovascular disease pathophysiology: strings attached. Eur Heart J Suppl. 2023;25(suppl A):A5-A11. doi:10.1093/eurheartjsupp/suac117

4. 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-E72. doi:10.1093/eurheartj/suaa064

5. Flu and people with heart disease or history of stroke. CDC. September 18, 2025. Accessed April 3, 2026. https://www.cdc.gov/flu/highrisk/heartdisease.html

6. Omidi F, Zangiabadian M, Shahidi Bonjar AH, Nasiri MJ, Sarmastzadeh T. Influenza vaccination and major cardiovascular risk: a systematic review and meta-analysis of clinical trials studies. Sci Rep. 2023;13(1):20235. doi:10.1038/s41598-023-47690-9

7. Yedlapati S, Khan S, Talluri S, et al. Effects of influenza vaccine on mortality and cardiovascular outcomes in patients with cardiovascular disease: a systematic review and meta-analysis. J Am Heart Assoc. 2021;10(6):e019636. doi:10.1161/JAHA.120.019636