Association between influenza vaccination and ischemic stroke risk in a population-based nested case-control study: The Vaccine Effectiveness, Networking, and Universal Safety (VENUS) Study.

BackgroundInfluenza vaccination may reduce the risk of infection-triggered ischemic stroke (IS), but evidence remains limited, particularly in Japan.MethodsThis nested case-control study examined the association between influenza vaccination and the occurrence of IS among persons aged ≥65 years in a Japanese municipality between October 2016 and September 2023. IS cases were identified from insurance claims and matched with controls based on sex, age, and month of IS occurrence. Conditional logistic regression was used to estimate the association between vaccination and IS occurrence while adjusting for covariates such as comorbidities and prescription drugs.ResultsA total of 21,476 IS cases and 107,360 matched controls were analyzed. Influenza vaccination was significantly associated with a lower odds of IS (reference: unvaccinated) when administered 0-14 days (odds ratio: 0.74, 95% confidence interval: 0.62-0.88), 15-30 days (0.51, 0.43-0.59), 31-60 days (0.50, 0.45-0.56), 61-90 days (0.79, 0.72-0.87), and 91-120 days (0.81, 0.73-0.89) before IS occurrence. In a subgroup analysis, this association was observed only during the pre-epidemic and epidemic phases. Sex- and age-stratified analyses revealed similar patterns, with some variation in the magnitude of association.ConclusionsThese findings suggest a possible short-term inverse association between influenza vaccination and IS risk in older adults, but the influence of residual confounding cannot be excluded. Further research is needed to confirm these findings and clarify the potential role of influenza vaccination in reducing IS risk.