The Bidirectional Relationship Between Coronary Artery Disease and Epilepsy: Cross-sectional and Prospective Cohort Studies from the UK Biobank

Background and aims: Coronary artery disease (CAD) is the leading cause of morbidity and mortality globally, while epilepsy is a common neurological disorder. Previous studies have compared the cardiovascular comorbidity burden in patients with epilepsy and their risk of cardiovascular mortality during follow-up. However, the bidirectional relationship between CAD and epilepsy remains unexplored. This study comprehensively assessed the association between CAD and epilepsy using cross-sectional and cohort designs in the UK Biobank and further investigated whether genetic susceptibility influences this link. Methods: This population-based study utilized UK Biobank data to investigate the relationship between epilepsy and CAD. A cross-sectional analysis of 502,359 participants was conducted using logistic regression to estimate odds ratios (ORs). In cohort 1 (n = 496,921 without baseline epilepsy), stratified Cox models assessed the risk of incident epilepsy by CAD status. In cohort 2 (n = 475,130 without baseline CAD), the risk of incident CAD by epilepsy status was similarly evaluated. Polygenic risk scores (PRS) for both CAD and epilepsy were constructed to explore genetic susceptibility. Results: The median age at baseline was 58.0 years, and 45.60% were male. During a median follow-up of 13.82 years for epilepsy and 13.73 years for CAD, 3,590 participants developed epilepsy and 39,223 developed CAD. In cross-sectional analysis, CAD was significantly associated with epilepsy. In Cohort 1, CAD was associated with higher epilepsy risk (HR: 1.29; 95% CI: 1.15?1.45; P < 0.001), and in Cohort 2, epilepsy was associated with higher CAD risk (HR: 1.34; 95% CI: 1.18?1.52; P < 0.001). These associations persisted across subgroups by age, sex, and BMI. Interestingly, CAD was linked to incident epilepsy only in participants with low genetic risk, while epilepsy predicted CAD only in those with high genetic susceptibility. Conclusions: Our findings indicate a bidirectional association between CAD and epilepsy, while also exploring the heterogeneity of this association across different subpopulations and its potential modification by genetic susceptibility. These results underscore the need for further studies to elucidate the underlying mechanisms and clinical implications of this association.