Risk of Cardiovascular Events After Influenza: A Population-Based Self-Controlled Case Series Study, Spain, 2011-2018

This study explores the relationship between influenza infection, both clinically diagnosed in primary care and laboratory confirmed in hospital, and atherothrombotic events (acute myocardial infarction and ischemic stroke) in Spain. A population-based self-controlled case series design was used with individual-level data from electronic registries (n = 2 230 015). The risk of atherothrombotic events in subjects >= 50 years old increased more than 2-fold during the 14 days after the mildest influenza cases in patients with fewer risk factors and more than 4-fold after severe cases in the most vulnerable patients, remaining in them more than 2-fold for 2 months. The transient increase of the association, its gradient after influenza infection, and the demonstration by 4 different sensitivity analyses provide further evidence supporting causality. This work reinforces the official recommendations for influenza prevention in at-risk groups and should also increase the awareness of even milder influenza infection and its possible complications in the general population. The risk of atherothrombotic events more than doubled during the 14 days following milder influenza cases in individuals with fewer risk factors. After severe cases in more vulnerable patients, it more than quadrupled, remaining elevated by 2-fold for 2 months.