Occupational Exposure to PM(2.5) and Incidence of Ischemic Heart Disease: Longitudinal Targeted Minimum Loss-based Estimation

BACKGROUND: We investigated the incidence of ischemic heart disease (IHD) in relation to accumulated exposure to particulate matter (PM) in a cohort of aluminum workers. We adjusted for time varying confounding characteristic of the healthy worker survivor effect, using a recently introduced method for the estimation of causal target parameters. METHODS: Applying longitudinal targeted minimum loss-based estimation, we estimated the difference in marginal cumulative risk of IHD in the cohort comparing counterfactual outcomes if always exposed above to always exposed below a PM(2.5) exposure cut-off. Analyses were stratified by sub-cohort employed in either smelters or fabrication facilities. We selected two exposure cut-offs a priori, at the median and 10th percentile in each sub-cohort. RESULTS: In smelters, the estimated IHD risk difference after 15 years of accumulating PM(2.5) exposure during follow-up was 2.9% (0.6%, 5.1%) using the 10th percentile cut-off of 0.10 mg/m(3). For fabrication workers, the difference was 2.5% (0.8%, 4.1%) at the 10th percentile of 0.06 mg/m(3). Using the median exposure cut-off, results were similar in direction but smaller in size. We present marginal incidence curves describing the cumulative risk of IHD over the course of follow-up for each sub-cohort under each intervention regimen. CONCLUSIONS: The accumulation of exposure to PM(2.5) appears to result in higher risks of IHD in both aluminum smelter and fabrication workers. This represents the first longitudinal application of targeted minimum loss-based estimation, a method for generating doubly robust semi-parametric efficient substitution estimators of causal parameters, in the fields of occupational and environmental epidemiology.