Impact of a comprehensive healthy lifestyle and genetic risk on arrhythmia: insights from the UK biobank study

Arrhythmias such as atrial fibrillation and bradyarrhythmia impose a substantial public health burden. Although genetic predisposition contributes to arrhythmia risk, the extent to which modifiable lifestyle factors may mitigate this risk remains unclear. This study aimed to evaluate the association between a comprehensive healthy lifestyle and incident arrhythmias, and to assess whether these associations differ across levels of genetic susceptibility. A prospective cohort analysis was conducted using 341,736 UK Biobank participants after excluding individuals with baseline arrhythmias and incomplete lifestyle information. A healthy lifestyle score (HLS) incorporating smoking status, alcohol consumption, diet quality, and physical activity was constructed. Incident arrhythmias were identified through ICD-10 and procedure codes. Cox proportional hazards models were used to estimate hazard ratios (HRs) for overall arrhythmia, atrial fibrillation, and bradyarrhythmia, adjusting for demographic and clinical covariates. Genetic susceptibility was quantified using a polygenic risk score (PRS) for atrial fibrillation, and joint lifestyle–genetic risk categories were used to evaluate their combined associations with AF risk. Over a mean follow-up of 10.9 years, 37,990 participants developed an incident arrhythmia, comprising 34,491 atrial fibrillation/flutter (AF) events and 9,399 bradyarrhythmia events; the composite count is a deduplicated union, so the two subtype counts overlap by 5,900 dual-subtype cases (Supplementary Table S4). Higher HLS values were associated with lower risks of overall arrhythmia and AF, whereas the association with bradyarrhythmia appeared weaker and non-monotonic. Compared with participants in the unfavorable lifestyle category, those in the favorable category had lower risks of AF (HR, 0.89; 95% CI, 0.87–0.91), overall arrhythmia (HR, 0.91; 95% CI, 0.89–0.94), and bradyarrhythmia (HR, 0.92; 95% CI, 0.87–0.97). The intermediate lifestyle category was also associated with lower risks of AF (HR, 0.92; 95% CI, 0.90–0.94), overall arrhythmia (HR, 0.93; 95% CI, 0.90–0.95), and bradyarrhythmia (HR, 0.94; 95% CI, 0.90–0.99). In joint-category analyses using participants with high genetic risk and an unfavorable lifestyle as the common reference group, the lowest AF risk was observed among individuals with both low genetic susceptibility and a favorable lifestyle. A competing-risks sensitivity analysis with non-arrhythmia death treated as a competing event preserved the direction and approximate magnitude of the lifestyle association for AF and overall arrhythmia (Supplementary Table S10): 10-year cumulative incidence in the favorable versus unfavorable categories was 5.85% versus 6.61% for AF and 6.44% versus 7.14% for overall arrhythmia. For bradyarrhythmia, 10-year cumulative incidence was numerically similar across lifestyle strata (1.64–1.72%), consistent with a residual contribution of differential survival to the observed bradyarrhythmia pattern (Supplementary Figure S1). A sensitivity analysis substituting the diet subscore with an AHA Life’s Essential 8-aligned cardiovascular-specific subscore produced directionally consistent estimates across all endpoints (Supplementary Table S8). In this large population-based cohort, adherence to a healthier lifestyle was associated with modestly lower risks of overall arrhythmia and atrial fibrillation. The association with bradyarrhythmia was weaker and appeared non-monotonic. These observational findings require confirmation in randomized lifestyle-intervention studies before causal inference.