A study published in Eurosurveillance indicates that influenza vaccination may reduce the risk of influenza-associated heart attack and stroke, even in individuals who contract the flu after vaccination. The research, conducted by Croci et al. in Denmark, analyzed data from over 1,200 adults aged 40 or older.
The study found that while influenza infection increases the short-term risk of cardiovascular events, prior vaccination was associated with a halving of this increased risk.
Background
Previous research has established that influenza infection elevates the short-term risk of cardiovascular conditions such as heart attack and stroke. It is also known that influenza vaccination can mitigate these risks by preventing the initial infection.
The objective of the Croci et al. study was to investigate whether the vaccine could reduce the increased risk of these cardiovascular events even if an infection occurred despite vaccination.
The researchers suggest that influenza infection acts as an acute trigger for cardiovascular events by inducing systemic inflammation, promoting a pro-thrombotic state, and destabilizing atherosclerotic plaques.
Study Methodology
The study utilized Danish health registry data collected between 2014 and 2025. It included 1,221 adults aged 40 or older who experienced their first-ever hospital admission for a heart attack or stroke within approximately one year (365 days) after a laboratory-confirmed influenza virus infection. The dataset encompassed all laboratory-confirmed influenza virus infections over nine consecutive influenza seasons.
Records for testing, hospitalization, vaccination status, and mortality were cross-referenced using Denmark's unique personal identifiers, linking data from the Danish National Health Registries, Danish Microbiology Database, National Patient Register, and Vaccination Register.
The researchers employed a self-controlled case series (SCCS) design, which compares event timing within the same individual. This method controls for time-invariant confounders such as comorbidities, genetic predisposition, and socioeconomic status.
Conditional Poisson regression was used to calculate incidence rate ratios (IRRs). A two-week pre-exposure period before testing was excluded to minimize reverse causality, where cardiovascular symptoms might have influenced testing. A negative exposure control using Campylobacter spp. infection was also conducted to support the specificity of the influenza findings.
Key Findings
The study population consisted of 660 males and 561 females, with a median age of 75 years. Among those included, 65% of hospitalizations were for a stroke, while 35% were for a heart attack.
Of the 1,231 PCR-confirmed influenza virus infections recorded, approximately half occurred in patients who had received the influenza vaccine for that season.
Key observations include:
- The risk for a first-time hospitalization due to heart attack or stroke was higher during the first week after testing positive for influenza compared to other periods before or after infection, with an overall incidence rate ratio (IRR) of 3.5.
- This risk increased threefold for stroke (IRR = 2.9) and fivefold for heart attack (IRR = 4.7). The peak IRR was 5.2 during days 1-3 post-infection, decreasing to 1.2 by days 15-28.
- For individuals who were infected but had been vaccinated for that influenza season, this elevated risk was reduced by half (50% reduction; interaction p = 0.020). Unvaccinated episodes showed an IRR of 4.7, while vaccinated episodes had an IRR of 2.4.
- Females showed a higher relative incidence (IRR = 4.7) compared to males (IRR = 2.5) during the primary risk period, although vaccination appeared protective in both groups.
Limitations
The study acknowledged several limitations:
- It did not account for potential variations in vaccine effectiveness, which can differ based on the match between vaccine formulation and circulating viral strains.
- It did not assess the impact of vaccination timing on outcomes.
- While gender-specific IRRs were reported, the study did not systematically assess the influence of gender as a variable on overall outcomes.
- The results may not be directly applicable to populations or settings with different influenza epidemiology, healthcare systems, or vaccination strategies.
Implications for Public Health
Croci et al. stated that if these findings are confirmed by further studies in different settings, they could support prioritizing influenza vaccination for individuals at risk of heart disease or stroke and inform revised recommendations across Europe.
The researchers suggested that emphasizing the dual protective effect of vaccination—against both infection and its cardiovascular complications—could have a substantial public health impact.
They also noted that integrating the vaccine's additional protection against these conditions into economic and burden analyses could strengthen the economic justification for influenza vaccination programs. Future research should integrate annual vaccine effectiveness data to refine risk estimates and inform public health recommendations.