Particulate Matter Exposure and Progression Trajectories of Cardiovascular Disease, Mood Disorders, Comorbidity, and Mortality: Associations and Underlying Metabolic Mechanisms

The role of particulate matter (PM) in the bidirectional relationship between cardiovascular disease (CVD) and mood disorders remains unclear. This UK Biobank-based study included participants without prior CVD or mood disorders at baseline with complete data. Outcomes included CVD and mood disorder incidences, comorbidity, and mortality. During a median 13.8-year follow-up, among 358,119 participants, 145,406 developed CVD, 27,318 mood disorders, 15,443 comorbidity, and 26,703 deaths. Multistate analysis showed PM_2.5 exposure significantly increased risks of progression in both trajectories. For trajectory 1, each IQR increase in PM_2.5 was associated with HRs (95% CI) of 1.219 (1.216-1.222), 1.080 (1.070-1.091), and 1.033 (1.013-1.053) for progression from baseline to CVD, CVD to comorbidity, and comorbidity to death, respectively. For trajectory 2, each IQR increase in PM_2.5 was associated with HRs (95% CI) of 1.227 (1.218-1.237), 1.024 (1.009-1.040), and 1.033 (1.013-1.053) for progression from baseline to mood disorders, mood disorders to comorbidity, and comorbidity to death, respectively. Similarly, PM₁₀ exposure showed weaker positive associations than PM_2.5. Lipoproteins and fatty acid metabolites primarily mediated disease progression in these trajectories. Our results demonstrated PM exposure contributes to progression from CVD and mood disorders to comorbidity and mortality, with different mediating metabolites identified at each stage of progression. These results highlight both the importance of PM control and the potential of metabolic pathways as targets for early intervention.