Abstract P656: Cardioembolic Risk Factors and Ischemic Stroke a Mendelian Randomization Analysis

Background: Cardioembolic stroke accounts for a large proportion of ischemic stroke. Observational studies have shown that several risk factors are associated with cardioembolic stroke. However, whether such associations reflect causality remains unknown. Objectives: We aimed to determine whether established and provisional cardioembolic risk factors are causally associated cardioembolic stroke, and whether they have pathways of causal influence on other ischemic stroke subtypes. Methods: Genetic instruments for atrial fibrillation (AF), myocardial infarction (MI), some electrocardiogram (ECG) indices and NT-pro BNP were obtained from large genetic consortiums. Summarized data of ischemic stroke and its subtypes were extracted from the MEGASTROKE consortium. Causal estimates were calculated by applying inverse variance-weighted analysis and other methods. Results: Genetically predicted AF was significantly associated with higher odds of ischemic stroke (OR 1.20, 95% CI 1.16-1.24, P=6.53х10 -30 ) and cardioembolic stroke (OR 1.95, 95% CI 1.85-2.06, P=8.81х10 -125 ). Genetically predicted MI was significantly associated with higher odds of large artery stroke (OR 1.487, 95% CI 1.25-1.77, P=9.53х10 -6 ). Suggestive associations were found between genetically determined resting heart rate and higher odds of ischemic stroke (OR 1.01, 95% CI 1.00-1.02, P=0.005), large artery stroke (OR 1.02, 95% CI 1.00-1.04, P=0.026) and cardioembolic stroke (OR 1.02, 95% CI 1.00-1.04, P=0.028). There was no causal association of P-wave terminal force in the precordial lead V1 (PTFVI), P-wave duration (PWD), N-terminal-pro-brain Natriuretic Peptide (NT-pro BNP) or PR interval with ischemic stroke or any subtypes. Conclusion: Genetic predisposition to AF and heart rate are associated with cardioembolic stroke. No evidence of causality relationship of MI, PTFVI, PWD, NT-pro BNP and PR interval on cardioembolic stroke is found.