Abstract
BACKGROUND: Ambient air pollution has been linked to atrial fibrillation (AF), yet the underlying metabolic mechanisms remain poorly understood. METHODS: We analyzed 227,324 UK Biobank participants without baseline AF. We constructed an air pollution score by aggregating all four pollutants (PM(2.5), PM(10), NO(2), NO(x)). Nuclear magnetic resonance metabolomics identified a pollution-related metabolic signature through elastic net regression. Associations between air pollutants, the metabolic signature and AF were analyzed using Cox models. Mediation analysis was employed to examine the role of the metabolic signature in the association between air pollutants and AF. RESULTS: During follow-up, 16,235 participants (7.14%) developed AF. We identified 65-metabolite signature significantly associated with air pollution, predominantly comprising lipoprotein lipid concentrations (32.31%), lipoprotein subclasses (15.38%), fatty acids (13.85%), and amino acids (12.31%). Each standard deviation increase in this metabolic signature was associated with 18% higher AF risk (HR = 1.18, 95%CI:1.03-1.35). The metabolic profile mediated 15.45% of the relationship between air pollution and AF, with lipoprotein parameters showing the strongest mediation effects. CONCLUSION: Air pollution-related metabolic signature was independently associated with AF risk and mediated a significant portion of pollution's arrhythmogenic effects. These findings provide novel insights into biological mechanisms linking environmental exposures to AF.