The Role of Influenza Vaccination in Cardiovascular Event Prevention
Researchers studied English patients with an acute cardiovascular event who received an influenza vaccine in the same 12-month period and compared that to the 120-day period after vaccination and the rest of the year. They observed those vaccinated were less likely to experience an acute cardiovascular event for 120 days after vaccine vs. the rest of the year.
This is a summarized version of the full in-depth article on Relias Media.
By Michael H. Crawford, MD, Editor. Professor of Medicine, Lucy Stern Chair in Cardiology, University of California, San Francisco.
Introduction
Influenza infection has long been associated with an increased risk of cardiovascular (CV) events, particularly in individuals with preexisting cardiovascular disease (CVD). Previous randomized controlled trials (RCTs) have shown that influenza vaccination can reduce CV morbidity and mortality in individuals with established CVD. However, no RCTs have investigated the potential of the flu vaccine for primary prevention of CV events in the general population. To address this gap, Davidson et al conducted a self-controlled case series (SCCS) study using linked electronic health records to examine the relationship between influenza vaccination and the risk of acute CV events.
Study Design and Methods
The SCCS design is particularly suited for this type of analysis because it uses each individual as their own control, thereby reducing confounding by fixed patient characteristics. This study used health records from more than 40 million individuals in England, aged 40 to 84 years, with data collected between Sept. 1, 2008, and Aug. 31, 2019. The study identified individuals who experienced a first acute CV event and had received an influenza vaccine within the 12 months following each September.
The primary outcome of interest was the occurrence of first acute CV events, which included myocardial infarction (MI), unstable angina, left ventricular heart failure, stroke, transient ischemic attack, and limb ischemia. To assess the effect of vaccination, the study analyzed the risk of acute CV events within 120 days post-vaccination, excluding the first 14 days, as influenza vaccines typically take two weeks to become fully effective.
Results
Study Population
The study included 193,900 individuals, 47% of whom were women. Among the participants, 89% had a high 10-year cardiovascular risk score (> 10%). These individuals were older and had higher mortality rates compared to those with lower risk scores.
Cardiovascular Event Reduction
The results demonstrated a significant reduction in the risk of first acute CV events following influenza vaccination:
- 15-28 days post-vaccination: A 28% reduction in the risk of CV events (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.70-0.74).
- 91-120 days post-vaccination: A sustained 17% reduction in CV event risk (HR, 0.83; 95% CI, 0.81-0.88).
The protective effect of the influenza vaccine was consistent across all age groups, individuals with varying levels of cardiovascular risk, and those at both high and low risk for CVD. Notably, younger participants (ages 40-64) showed a more pronounced reduction in risk during the early post-vaccination period.
Commentary and Interpretation
Mechanisms and Comparisons with Other Interventions
The reduction in acute CV events following influenza vaccination is comparable to that seen with established CV preventive measures such as statins and angiotensin-converting enzyme (ACE) inhibitors. The highest protective effect was observed for the prevention of myocardial infarction (MI), with a 40% risk reduction within the first 15-28 days post-vaccination (odds ratio, 0.60). These findings suggest that influenza vaccination may offer substantial cardioprotective benefits beyond its role in preventing influenza.
The exact mechanisms by which influenza vaccination reduces CV events are not fully understood. One hypothesis is that the vaccine may have pleiotropic effects, potentially triggering heterologous immune responses that reduce systemic inflammation. Inflammation plays a critical role in the pathophysiology of acute CV events, particularly in the destabilization of atherosclerotic plaques, which can lead to myocardial infarction or stroke. By reducing inflammation, the influenza vaccine may lower the risk of these acute events.
Study Strengths
The SCCS design was a major strength of the study, as it minimized confounding by controlling for fixed individual characteristics such as genetics or baseline health status. By using individuals as their own controls, the study was able to more accurately assess the temporal relationship between influenza vaccination and the risk of acute CV events. Additionally, the large dataset covering more than 40 million people made the results highly representative of the general population.
Seasonal adjustment was another key aspect of the study design. The authors accounted for the fact that influenza season typically occurs between December and March in the Northern Hemisphere, ensuring that the reduction in CV events was not merely due to seasonality. By comparing warm months (April-September) with cooler months (October-March), the authors confirmed that the protective effect of the influenza vaccine persisted irrespective of season.
Limitations
Despite its strengths, the SCCS method does have limitations. While it eliminates confounding by fixed patient characteristics, it does not account for time-varying factors such as acute illness, healthcare access, or other environmental variables that might influence both vaccination timing and CV event risk. Additionally, the healthy user bias may have influenced results, particularly among younger individuals who were more likely to receive the vaccine and subsequently show lower event rates.
The relatively short follow-up period also limits the conclusions that can be drawn about the long-term cardiovascular benefits of influenza vaccination. While the study showed a reduction in acute CV events within 120 days of vaccination, it remains unclear whether this benefit extends beyond this timeframe.
Summary
Davidson et al's SCCS study provides compelling evidence that influenza vaccination reduces the risk of first acute CV events, including MI, stroke, and unstable angina. This protective effect was seen across age groups and CV risk levels, highlighting the potential for influenza vaccination as both a primary and secondary preventive measure in CV health.
Given the magnitude of the risk reduction observed, influenza vaccination should be strongly recommended, particularly for individuals at high risk for CVD. Future studies should explore the long-term CV benefits of influenza vaccination and further investigate the underlying mechanisms that drive this protective effect. Nonetheless, the current evidence supports the integration of influenza vaccination into broader CV prevention strategies, particularly during flu season.
Read the full in-depth article on Relias Media
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