Trigger Factors In Patients With A Patent Foramen Ovale Associated Stroke: A Case-Crossover Study

Background: Patent foramen ovale (PFO) is a congenital anatomical variant which is associated with strokes in young adults. Contrary to vascular risk factors and atherosclerosis, a PFO is present from birth. However, it is completely unknown how an anatomical structure that is already present at birth in a large proportion of the population, can convert into a PFO that causes stroke in a few. Recent studies reported a significant association between certain trigger factors and ischemic stroke in young adults. This study aims to investigate these triggers in PFO-associated stroke. Methods: The ODYSSEY Study, a multicenter prospective cohort study between 2013 and 2021, included patients aged 18-49 years experiencing their first-ever ischemic event. Participants completed a questionnaire about exposure to potential trigger factors. A case-crossover design was used to assess the relative risks (RR) with 95% confidence intervals (95% CI). The primary outcome was the relative risk of potential trigger factors for PFO-associated stroke. Results: 1043 patients completed the questionnaire and had an ischemic stroke of which 124 patients had a PFO-associated stroke (median age 42.1 years, 45.2% men). For patients with PFO-associated stroke the RR was 26.0 (95% CI 8.0-128.2) for fever, 24.2 (95% CI 8.5-68.7) for flu-like disease and RR 3.31 (95% CI 2.2-5.1) for vigorous exercise. Conclusion: In conclusion, flu-like disease, fever and vigorous exercise may convert an asymptomatic PFO into a stroke causing PFO in young adults.