title: Occupational Exposure to PM2.5 and Incidence of Ischemic Heart Disease: Longitudinal Targeted Minimum Loss-based Estimation.
abstract: 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 PM2.5 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 PM2.5 exposure during follow-up was 2.9% (0.6%, 5.1%) using the 10th percentile cut-off of 0.10 mg/m. For fabrication workers, the difference was 2.5% (0.8%, 4.1%) at the 10th percentile of 0.06 mg/m. 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 PM2.5 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.
authors.affiliation: From the aDepartment of Biostatistics, bDepartment of Environmental Health Sciences, University of California Berkeley, Berkeley, CA; and cDepartment of Internal Medicine, Stanford University School of Medicine, Stanford, CA.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Brown
authors.forename: Maya
authors.initials: M
authors.lastname: Petersen
authors.forename: Sadie
authors.initials: S
authors.lastname: Costello
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Noth
authors.forename: Katherine
authors.initials: K
authors.lastname: Hammond
authors.forename: Mark
authors.initials: M
authors.lastname: Cullen
authors.forename: Mark van der
authors.initials: Mv
authors.lastname: Laan
authors.forename: Ellen
authors.initials: E
authors.lastname: Eisen
mesh_terms: D000328:Adult; D000535:Aluminum; D015331:Cohort Studies; D005260:Female; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D066192:Manufacturing Industry; D008669:Metallurgy; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000453:epidemiology*; D016273:Occupational Exposure / Q000706:statistics & numerical data*; D052638:Particulate Matter; D012044:Regression Analysis; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
chemical_list: D052638:Particulate Matter; D000535:Aluminum