Association between influenza vaccination and risk of stroke in Alberta, Canada: a population-based study.

Background: Respiratory infection can be an immediate precursor to stroke and myocardial infarction. Influenza vaccination is associated with reduced risk of myocardial infarction and hospitalisation for cardiac disease, and influenza vaccination is strongly recommended for patients with heart disease. Evidence on whether the same protective association exists for stroke, and whether this potential effect is consistent across age and risk groups, is conflicting. We aimed to assess the risk of stroke after influenza vaccination in adults.

Methods: We obtained administrative data from the Alberta Health Care Insurance Plan (which covers all residents of Alberta, Canada) beginning on Sept 30, 2009, or May 15 of the year in which residents were recorded as being 18 years of age. Individuals were censored at the earliest of three events: death, recorded outmigration, or Dec 31, 2018. The outcome of interest was any stroke event, comprising acute ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and transient ischaemic attack. We used Andersen-Gill Cox models to analyse the hazard of any stroke event for individuals with recent (<182 days) influenza vaccination compared with those without recent influenza vaccination, with adjustment for age, sex, anticoagulant use, atrial fibrillation, chronic obstructive pulmonary disease, diabetes, hypertension, income quintile, and rural or urban home location. Two-way interaction terms between each individual covariate and vaccination status were used to assess for effect modification by risk factor. The association between vaccination and risk of each type of stroke was also modelled, adjusting for baseline covariates.

Findings: The study sample consisted of 4 141 209 adults (29 687 899 person-years of observation time) registered under the provincial health-care system between Sept 30, 2009, and Dec 31, 2018. 1 769 565 (42·73%) individuals received at least one vaccination during the study period, and 38 126 stroke events were recorded. Adjusted for demographics and comorbidities, recent influenza vaccination significantly reduced the hazard of stroke (hazard ratio 0·775 [95% CI 0·757-0·793]). This association persisted across all stroke types. We found effect modification by each covariate examined except for home location; however, vaccination was associated with a reduced risk of stroke overall across all ages and risk profiles with the exception of individuals without hypertension.

Interpretation: The risk of stroke is reduced among people who have recently been vaccinated against influenza compared with those who have not. This association extended to the entire adult population and was not limited to individuals with a baseline high risk of stroke. Further studies in a variety of settings are needed to evaluate whether influenza vaccination could be used as a public health strategy to prevent stroke.

Funding: None.