Influenza vaccination attenuates acute myocardial infarction and stroke risk following influenza infection: a register-based, self-controlled case series study, Denmark, 2014 to 2025

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Abstract
BACKGROUND: Influenza infection is a recognised trigger of acute myocardial infarction (AMI) and stroke, but whether influenza vaccination modifies this risk remains unclear. AIM: We aimed to quantify the short-term cardiovascular risk after laboratory-confirmed influenza infection and assess whether vaccination attenuates it. METHODS: We conducted a nationwide self-controlled case series study using Danish health registries (2014–2025) and included individuals aged ≥ 40 years with a first-ever hospital admission for AMI or stroke within ± 365 days of a PCR-confirmed influenza infection. We defined days 1–7 after specimen date as the risk period and excluded a 14-day pre-exposure period to reduce reverse causality, where influenza testing might be prompted by cardiovascular disease symptoms. We linked testing, hospitalisation, vaccination and mortality data deterministically via unique personal identifiers. We estimated incidence rate ratios (IRRs) and 95% confidence intervals (CI) with conditional Poisson regression. RESULTS: Among 1,221 individuals with a first-ever AMI (n = 429; 35%) or stroke (n = 792; 65%), median age was 75 years (interquartile range: 66–82); 561 (46%) were female. After calendar-month adjustment, the IRR for cardiovascular events during the risk period was 3.5 (95% CI: 2.6–4.7), higher for AMI (IRR = 4.7; 95% CI: 3.1–7.4) than stroke (IRR = 2.9; 95% CI: 2.0–4.2). Prior influenza vaccination during the same influenza season, recorded in 610 (50%) episodes, reduced the excess risk of AMI or stroke associated with influenza infection (interaction p = 0.020). CONCLUSIONS: Influenza infection conferred a transiently increased risk of first-time AMI and stroke. Vaccination substantially attenuated this risk, supporting its role in preventing cardiovascular complications after breakthrough infection.

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