In the US alone, new strains of influenza reliably emerge to kill tens of thousands of older people every year, hundreds of thousands in a bad year. The research and development community has yet to fully develop and deploy any of the possible approaches that might effectively shut down viral infections, such as descendants of the DRACO technology, and the aged immune system becomes ever less able to resist and control infections of all sorts. In later life, the immune system also becomes more inflammatory, more vulnerable to runaway inflammation during infection that leads to sepsis. Further, other aspects of aging make organs and tissues less able to resist the stresses that result from severe infection and accompanying inflammation.
One of the ways in which influenza infection and accompanying inflammation kills older people is by provoking what is known as a major adverse cardiovascular event, meaning a heart attack or stroke, that would otherwise not have occurred. One of the ways that influenza vaccination can help to reduce mortality is by preventing evident infection and all of its consequences. Another, as shown in today’s open access paper, is by reducing the severity of the infection, the stress placed upon organ systems, and thus the risk of fatal heart attack and stroke. There are many good reasons to maintain a vaccination schedule in late life, even given the reduced capacity of the aged immune system, and this is one of them.
Influenza infection can trigger acute cardiovascular events through short-lived systemic inflammation that favours a pro-thrombotic state and destabilises vulnerable atherosclerotic plaques. Self-controlled case series studies, which compare event rates within individuals during prespecified risk time windows against their own baseline time, have consistently shown transient increases in cardiovascular risk after laboratory-confirmed influenza. A Canadian study reported a sixfold increase in acute myocardial infarction risk during the first 7 days after positive test results (incidence rate ratio (IRR) = 6.05); estimates from Spain and the Netherlands are similar. Studies employing finer temporal resolution have further characterised the risk profile, indicating that peak incidence increases within 3 days, then tapers back within 2-4 weeks.
Among mounting evidence suggesting that influenza vaccination reduces cardiovascular risk, a recent meta-analysis of randomised controlled trials estimated 32% lower risk. Two successive self-controlled case-series studies in the United Kingdom demonstrated a 20-23% reduced incidence for both acute myocardial infarction and stroke. In particular, the second study reported no evidence of sex-specific differences, and effects were slightly stronger among people vaccinated early in the influenza season. A meta-analysis including these same two studies provided further evidence of the protective effect of vaccination (pooled IRR = 0.84 for acute myocardial infarction).
In this self-controlled case series study in Denmark spanning 2014 to 2025, PCR-confirmed influenza was followed by a sharp, transient rise in the first-ever hospitalisations for acute myocardial infarction and stroke. Risk concentrated in the first week, peaking within 3 days, and declined back to baseline by 2 weeks. Prior influenza vaccination was associated with a significantly lower excess risk. This temporal profile aligns with studied mechanisms. Influenza infection has been shown to precipitate atherogenesis and has been epidemiologically linked to acute myocardial infarction and stroke in adults 40 years and older.
Vaccination can plausibly mitigate these effects by priming adaptive immunity and reducing viral replication, thereby dampening systemic inflammatory peaks. By vaccination status, the adjusted IRRs for cardiovascular events in this study were 4.7 and 2.4 for unvaccinated and vaccinated episodes, respectively. To our knowledge, this is the first study to show statistically significant attenuation of post-influenza cardiovascular risk by vaccination. A Canadian study observed similar results but possibly lacked statistical power to confirm them.
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