Abstract
Myocardial infarctions have been associated with PM(2.5), and more recently with NO(2) and O(3), however counterfactual designs have been lacking and argument continues over the extent of confounding control. Here we introduce a doubly robust, counterfactual-based approach that deals with nonlinearity and interactions in associations between confounders and both outcome and exposure, as well as a double negative controls approach that capture omitted confounders. We used data from over 4 million admissions for myocardial infarction in the US Medicare population between 2000 and 2016 and linked them by ZIP code of residence to high resolution predictions of annual PM(2.5), NO(2,) and O(3). We computed the counts of admissions for each ZIP code-year. In the doubly robust approach, we divided each pollutant into deciles, and for each decile, we fitted a gradient boosting machine model to estimate the effects of covariates, including the co-pollutants, on the counts. We used these models to predict, for all ZIP code-years, the expected counts had everyone be exposed in that decile. We also estimated the probability of being in that decile given all covariates, again with a gradient boosting machine, and used inverse probability weights to compute the weighted average rate of MI admission in each decile. In the negative control approach, for each pollutant, we fitted a quasi-Poisson model to estimate the exposure effect, adjusting for covariates including the co-pollutants, and negative exposure and outcome controls to control for unmeasured confounding. Each 1-μg/m(3) increase in annual PM(2.5) increased the admission for MI by 1.37 cases per 10,000 person-years (95% CI: 1.20, 1.54) in the doubly robust approach, and by 0.69 cases (95% CI 0.60, 0.78) using the negative control approach. Elevated risks were seen even below annual PM(2.5) level of 8 μg/m(3). Results for NO(2) and O(3) were inconsistent.