The joint effects of multiple air pollutants, genetic susceptibility, and their interactions on incident cardiovascular disease, arrhythmia, and mortality

This study assessed combined effects of air pollutants on arrhythmia, cardiovascular disease (CVD), and mortality, and explored genetic susceptibility’s role. In 435,893 participants from the UK Biobank, air pollutant concentrations (PM 2.5 , PM 2.5–10 , PM 10 , NO 2 , and NO) were obtained from established land-use regression models linked to the database.An air pollution scores integrated pollutant levels weighted by CVD/arrhythmia-associated coefficients from single-pollutant Cox models. Genetic risk scores (GRS) and pollutant-attributable fractions (PAFs) were analyzed, with GRS primarily examined in the context of gene–pollution interactions rather than as an independent risk factor. Over 12.7 median follow-up years, 56,354 incident arrhythmia cases occurred. Adjusted models showed higher quartiles of NO 2 , NO, and PM 2.5 increased risks of arrhythmia, CVD, and mortality (all P-trend <0.001; P-trend indicated trend tests across increasing exposure categories). Men exhibited weaker associations between pollution scores and arrhythmia/CVD than women. NO 2 was the primary risk factor for arrhythmia RR:1.04 (1.01–1.08); PAF=3.45% and CVD RR:1.11 (1.08–1.14); PAF=8.11%, while NO and PM 2.5 dominated CVD mortality RR:1.20 (1.08–1.33); PAF=13.62% and all-cause mortality RR:1.10 (1.06–1.13); PAF=7.10%, respectively. Furthermore, significant interactions were observed between air pollution and GRS, indicating higher susceptibility among individuals with elevated genetic risk. Combined exposure to five pollutants heightened arrhythmia, CVD, and mortality risks, with NO 2 as the key driver for arrhythmia/CVD. Genetic susceptibility modified pollution-related risks. Mitigating air pollution, particularly NO 2 , may reduce cardiovascular burden.