Long-term exposure to ambient PM_2.5 and mortality: A comparison of between-subjects and within-subjects survival...

Cohort studies have reported positive associations between long-term exposure to ambient fine particles (PM_2.5) and mortality. However, there is heterogeneity across results that may be due to unmeasured and residual confounding. We aim to compare two distinct types of analysis to examine whether long-term exposure to air pollution is associated with all-cause and ischemic heart disease (IHD) mortality: (i) a traditional survival analysis that contrasts different individuals at similar times, and (ii) a self-controlled design that controls for time-invariant confounders by contrasting the same person at different times.

We used an open population-based cohort created from health administrative databases. The cohort included all adults older than 20 years living in the province of Quebec, Canada, between 2002 and 2017. We assessed long-term exposure to ambient PM_2.5 using annual mean concentrations estimated from satellite-based model. We assigned time-varying annual exposures to individuals based on their residential postal code. For both types of analyses, we estimated the association with all-cause and IHD mortality using Cox proportional hazard models adjusted for age, time-varying neighborhood socioeconomic status, and current year.

The cohort included 7,506,027 individuals, with 996,665 and 231,376 deaths from all causes and IHD, respectively. In the between-subjects analysis, hazard ratios from linear models were 1.03 (95% confidence interval [CI]: 1.02, 1.03) for all-cause and 1.04 (95% CI: 1.03, 1.05) for IHD per interquartile range (3.3 µg/m³). In the within-subjects analysis, hazard ratios were 1.06 (95% CI: 1.04, 1.08) for all-cause and 1.06 (95% CI: 1.00, 1.11) for IHD per interquartile range increase in the difference between event and referent years (1.9 µg/m³). However, we found evidence of nonlinearity, with a steeper slope at lower concentrations.

Consistently across the two designs, we found positive associations between annual mean exposure to low level of ambient PM_2.5 and mortality. However, the magnitude of the association varied depending on the statistical design.