UC San Diego

Background Long-term exposure to outdoor fine particulate matter (PM_2.5) is the leading environmental risk factor for premature mortality worldwide. Characterizing important pathways through which PM_2.5 increases individuals' mortality risk can clarify the PM_2.5-mortality relationship and identify possible points of interventions. Recent evidence has linked PM_2.5 to the onset of diabetes and cardiovascular disease, but to what extent these associations contribute to the effect of PM_2.5 on mortality remains poorly understood. Methods and Results We conducted a population-based cohort study to investigate how the effect of PM_2.5 on nonaccidental mortality is mediated by its impacts on incident diabetes, acute myocardial infarction, and stroke. Our study population comprised ≈200 000 individuals aged 20 to 90 years who participated in population-based health surveys in Ontario, Canada, from 1996 to 2014. Follow-up extended until December 2017. Using causal mediation analyses with Aalen additive hazards models, we decomposed the total effect of PM_2.5 on mortality into a direct effect and several path-specific indirect effects mediated by diabetes, each cardiovascular event, or both combined. A series of sensitivity analyses were also conducted. After adjusting for various individual- and neighborhood-level covariates, we estimated that for every 1000 adults, each 10 μg/m³ increase in PM_2.5 was associated with ≈2 incident cases of diabetes, ≈1 major cardiovascular event (acute myocardial infarction and stroke combined), and ≈2 deaths annually. Among PM_2.5-related deaths, 31.7% (95% CI, 17.2%-53.2%) were attributable to diabetes and major cardiovascular events in relation to PM_2.5. Specifically, 4.5% were explained by PM_2.5-induced diabetes, 22.8% by PM_2.5-induced major cardiovascular events, and 4.5% through their interaction. Conclusions This study suggests that a significant portion of the estimated effect of long-term exposure to PM_2.5 on deaths can be attributed to its effect on diabetes and cardiovascular diseases, highlighting the significance of PM_2.5 on deteriorating cardiovascular health. Our findings should raise awareness among professionals that improving metabolic and cardiovascular health may reduce mortality burden in areas with higher exposure to air pollution.