ABSTRACT The proposed project is responsive to PA-13-302. The objective of this proposal is to extend our work on the health effects of occupational exposures to particulate matter. We will extend follow-up of incident IHD in the active cohort for 5 more years (total of 20 years) and follow subjects past termination of employment, linking the cohort to Medicare claims and cause specific mortality. Aim 1: Develop job-exposure matrices (JEMs) for PM and selected chemicals based on job-level exposures rather than distinct exposure groups (DEGs), adjusting for respirator use. Aim 2: Examine the impact of co- exposure to chemicals and physical stressors—noise and heat—as well as job stress, as independent risk factors for IHD incidence, and as potential confounders, intermediates and effect modifiers of the cardiovascular effects of PM2.5 exposure among all active workers in aluminum smelters and fabrication facilities. Aim 3: Explore the contribution of plant level, community and early life social and environmental characteristics to the incidence of cardiovascular disease. Aim 4: Estimate the associations between cumulative exposure to PM2.5 (as well as the coarse particle fraction PM2.5 - PM10) and longitudinal decline in pulmonary function. Aim 5: Examine the relationships between cumulative exposure to PM2.5, chemicals and COPD and CVD mortality, taking account of health status (risk score while actively employed) and new information on health status after age 65 (after leaving work) derived from linked Medicare claims files. Viewed altogether, continuation of the Alcoa study with the assembled team of investigators provides an unparalleled opportunity to address a host of critical empiric and methodologic issues previously unapproachable. In addition to understanding better what aspects of PM exposure contribute to acute and chronic risk of IHD, COPD and accelerated pulmonary function decline, we can learn how PM interacts with the most ubiquitous of workplace co-exposures as well as the contributions of personal, plant level and social determinants by applying state-of-the-art methods in measurement science and epidemiology.

PROJECT NARRATIVE The Alcoa research infrastructure—linking quantitative exposure measures to myriad hazards of active workers whose behavior, social environment and health status from pre-employment through retirement to death are fully observed-- provides a unique opportunity to extend our work on the health effects of occupational exposures to small particles (PM2.5). We will extend follow-up of incident ischemic heart disease in the active cohort for 5 more years (total of 20 years) and follow subjects past termination of employment, linking the cohort to Medicare claims and cause specific mortality.