Abstract A135: Both High And Low Physical Activity Levels Are Associated With An Increased Risk Of Early-Onset Cryptogenic Ischemic Stroke

Introduction: There is scarce data on the association of low physical activity (PA) with cryptogenic ischemic stroke (CIS), particularly among young adults with distinct PA patterns and intensities compared to elderly stroke patients. This study aims to investigate the relationship between levels of PA and early-onset CIS, stratified by the presence of a high-risk patent foramen ovale. Methods: We included patients aged 18-49 years with a first-ever CIS, along with sex- and age-matched stroke-free controls from 19 European centers. All enrolled patients received a thorough and standardized diagnostic evaluation to exclude known causes of stroke. PA levels were measured using the short form of the International Physical Activity Questionnaire, resulting in Metabolic Equivalents, analyzed as percentiles: bottom 10%, 10–25%, 25–75%, 75–90%, and top 10%, with the middle 25–75% percentile group serving as the reference category representing at least moderate but not extremely vigorous PA. To account for potential imbalances between cases and controls, conditional logistic regression was performed, adjusting for age, education level, traditional risk factors, and non-traditional risk factors. Results: Altogether, 531 patients (median age 41 [interquartile range 34-46]; 47.3% women) and 531 controls were included. Scoring in the top 10% of PA was independently associated with CIS: adjusted odds ratio 2.07; 95% confidence interval 1.22-3.51. Comparing patients without high-risk patent foramen ovale to all controls, top 10% PA category (1.78; 1.07-2.94), and the bottom 10% category (1.76; 1.06-2.92) were associated with CIS. When comparing patients with high-risk patent foramen ovale to all controls, independent association was not found for any PA category in the fully adjusted model. Conclusion: PA in the top 10% was associated with an increased risk of early-onset CIS in the overall study population. Among patients without a high-risk patent foramen ovale, both the bottom 10% and top 10% of PA, compared to intermediate levels (25–75%), were consistently associated with elevated CIS risk. These findings highlight the need to better understand the mechanisms through which both very low and very high activity levels may predispose to stroke, and to identify inherited or acquired factors that place certain individuals at greater risk.