Life-course exposure to PM2.5 components and genetic susceptibility on the risk of atrial fibrillation and subsequent heart failure

AIMS: The life-course joint effects of specific fine particulate matter (PM2.5) components and genetic susceptibility on the progression from atrial fibrillation (AF) to heart failure (HF) remain uncertain. We aimed to investigate these associations for both incident AF and its subsequent progression to HF. METHODS AND RESULTS: In this prospective study of 464 541 UK Biobank participants, we estimated life-course residential exposures to PM2.5 and its key components-including elemental carbon (EC), organic carbon (OC), ammonium (NH₄⁺), nitrate (NO₃⁻), and sulfate (SO₄²⁻)-using a validated spatiotemporal model, and constructed a polygenic risk score for AF and HF. We used Cox models to assess non-linear associations and gene-environment (G × E) interactions on both additive and multiplicative scales and quantile-based g-computation to evaluate mixture effects. During follow-up for a median 12.3-years (IQR: 11.70, 13.23), 27 655 participants (mean age 56.5, SD 8.1; 54.8 female) developed AF, with 12.3% progressing to HF. Life-course exposure to components such as EC was associated with increased risks for both incident AF (HR per 1-SD increase: 1.03; 95% CI: 1.02, 1.04) and progression to HF (HR: 1.04; 95% CI: 1.01, 1.08), often with non-linear threshold effects. We also identified a stage-dependent G × E interaction, shifting from a significant multiplicative interaction for incident AF to an additive interaction for the progression to HF, with a relative excess risk due to interaction of up to 0.46. CONCLUSION: Our findings highlight that minimizing cumulative pollution exposure is crucial for preventing incident AF and subsequent HF, especially in genetically susceptible individuals, guiding precision prevention strategies.