Air pollution, genetic susceptibility, and the risk of ventricular arrhythmias: a prospective cohort study in the UK Biobank

Abstract Aims Both genetic and environmental factors contribute to the development of ventricular arrhythmias (VAs). However, the extent to which genetic susceptibility modifies the effects of air pollutants on the risk of VAs remains poorly understood. Methods and results This study included 491 305 participants without VAs at baseline from UK Biobank. Exposure to ambient air pollutants, including particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOX), was estimated through land use regression modelling. The associations between air pollutants and the incidence of VAs were then investigated using a Cox proportional hazards model adjusted for covariates. Additionally, we established a polygenic risk score for VAs and assessed the joint effect of genetic susceptibility and air pollution on incident VAs. During a median follow-up of 14.3 years, 4333 participants were diagnosed with VAs. Increased long-term exposure to PM2.5, PM10, NO2, and NOx was significantly associated with higher risks of VAs, with hazard ratios (HRs) per quintile increase of 1.07 (95% confidence interval, 95% CI: 1.03–1.11), 1.07 (1.03–1.11), 1.10 (1.06–1.14), and 1.08 (1.05–1.12) for each pollutant, respectively. Notably, there were significant additive interactions between air pollutants and genetic risk. Participants with both high genetic risk and high exposure to air pollution exhibited the greatest risk of VAs, with the highest HRs observed for PM2.5 (HR, 4.51; 95% CI, 3.66–5.56), PM10 (HR, 4.28; 95% CI, 3.52–5.22), NO2 (HR, 4.90; 95% CI, 3.97–6.03), and NOx (HR, 4.56; 95% CI, 3.72–5.60), respectively. Conclusion Long-term exposure to air pollution is associated with an increased risk of VAs, especially in individuals with a high genetic risk.