A study by Croci et al. investigates the relationship between influenza infection, influenza vaccination, and the short-term risk of acute cardiovascular events, specifically acute myocardial infarction (AMI) and stroke. Using comprehensive Danish national health registries, the authors conducted a nationwide self-controlled case series study covering the period from 2014 to 2025. The primary aim was to quantify the transient cardiovascular risk following laboratory-confirmed influenza infection and to determine whether prior influenza vaccination attenuates this risk.
Cardiovascular diseases remain a major global health burden, and influenza infection has been recognised as a trigger for acute cardiovascular events. The proposed mechanism involves systemic inflammation leading to a pro-thrombotic state and destabilisation of atherosclerotic plaques. While previous studies have shown that influenza vaccination reduces cardiovascular risk by preventing infection, it has been unclear whether vaccination also mitigates the severity of cardiovascular complications in individuals who become infected despite vaccination.
The study included Danish residents aged 40 years or older who had at least one PCR-confirmed influenza infection and a first-ever hospital admission for AMI or stroke within a ±365-day observation window around the infection.
The exposure was defined as the date of specimen collection for a positive influenza PCR test (day 0). The primary risk period was defined as days 1–7 following infection, reflecting the hypothesised window of highest cardiovascular vulnerability. A 14-day pre-exposure period was excluded to minimise reverse causality, as influenza testing might be prompted by early cardiovascular symptoms. The control period consisted of all remaining observation time.
The final study population comprised 1,221 individuals with 1,231 influenza infection episodes. The median age was 75 years, and 46% were female. Of the cardiovascular events, 65% were strokes and 35% were AMI. Approximately half of the infection episodes (50%) occurred in individuals who had received influenza vaccination during the same season, defined as vaccination at least 14 days prior to infection.
The primary analysis demonstrated a markedly increased risk of cardiovascular events immediately following influenza infection. During the 7-day risk period, the adjusted incidence rate ratio (IRR) for AMI or stroke was 3.5, indicating a more than threefold increase compared with baseline periods. The risk was higher for AMI (IRR 4.7) than for stroke (IRR 2.9).
Previous influenza vaccination significantly attenuated this excess risk. Among unvaccinated episodes, the adjusted IRR was 4.7, whereas among vaccinated episodes it was 2.4. This corresponds to approximately a 50% reduction in excess cardiovascular risk among vaccinated individuals, with a statistically significant interaction.
Temporal analyses revealed that the risk peaked within the first three days after infection (IRR 5.2) and declined rapidly, returning to baseline within two to four weeks. This pattern is consistent with the biological hypothesis of acute inflammatory and thrombotic responses triggered by infection.
A range of additional and sensitivity analyses confirmed the robustness of the findings. These included varying the observation window, redefining control periods, excluding in-hospital influenza testing, and shifting the index date to approximate symptom onset. In all cases, the elevated cardiovascular risk persisted, and vaccination remained associated with lower excess risk.
Negative control analyses were also conducted to assess potential confounding. No association was found between influenza and unrelated outcomes such as retinal detachment, supporting the specificity of the findings. However, an unexpected increase in cardiovascular risk was observed following Campylobacter infection, suggesting that severe infections in general may trigger inflammatory pathways leading to cardiovascular events. Influenza vaccination did not modify this risk, reinforcing that the observed protective effect is specific to influenza.
Subgroup analyses showed broadly consistent results across sex, age groups, and event types, although some subgroup estimates were imprecise due to small numbers. The attenuation effect of vaccination was observed in both AMI and stroke, although statistical significance was not always reached for individual outcomes.
Overall, this study provides strong evidence that influenza infection is associated with a substantial, short-term increase in the risk of first-time AMI and stroke, particularly within the first week after infection. Influenza vaccination significantly attenuates this excess risk, even among individuals who experience breakthrough infections. These findings highlight a dual benefit of influenza vaccination: prevention of infection and reduction of its cardiovascular complications. The results support current recommendations to prioritise influenza vaccination in individuals at high cardiovascular risk and suggest that its public health value may be greater than previously recognised.
Source: Eurosurveillance
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