Chronic Exposure to Fine Particulate Matter Increases Mortality Through Pathways of Metabolic and Cardiovascular Disease: Insights From a Large Mediation Analysis.

Background Long-term exposure to outdoor fine particulate matter (PM2.5) is the leading environmental risk factor for premature mortality worldwide. Characterizing important pathways through which PM2.5 increases individuals' mortality risk can clarify the PM2.5-mortality relationship and identify possible points of interventions. Recent evidence has linked PM2.5 to the onset of diabetes and cardiovascular disease, but to what extent these associations contribute to the effect of PM2.5 on mortality remains poorly understood. Methods and Results We conducted a population-based cohort study to investigate how the effect of PM2.5 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 PM2.5 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 PM2.5 was associated with ≈2 incident cases of diabetes, ≈1 major cardiovascular event (acute myocardial infarction and stroke combined), and ≈2 deaths annually. Among PM2.5-related deaths, 31.7% (95% CI, 17.2%-53.2%) were attributable to diabetes and major cardiovascular events in relation to PM2.5. Specifically, 4.5% were explained by PM2.5-induced diabetes, 22.8% by PM2.5-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 PM2.5 on deaths can be attributed to its effect on diabetes and cardiovascular diseases, highlighting the significance of PM2.5 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.