Increased risk of cardiovascular disease (CVD) related to particulate matter (PM) in air pollution has become a major public health concern in the US and worldwide. However, while exposure to particles of combustion and crustal origin are prevalent in industrial work, in concentrations up to 2-3 orders of magnitude higher than those associated with CVD in the ambient environment, evidence regarding occupational-related heart disease risk associated with PM exposure is scant. We propose to examine CVD incidence and mortality in a cohort of approximately 75,000 workers exposed to PM2.5 of varying composition and concentration, who has been under intense observation for over a decade as part of the PI's ongoing studies at a major Aluminum Company. As a consequence of these ongoing studies, the investigators have in-hand and fully linked unparalleled information on individual social (e.g. income, education, savings) and behavior (e.g. smoking, BMI, cholesterol) risks, work exposure profiles including all physical, chemical and psycho-social factors of relevance (e.g. heat, noise, strain), complete health claims files since 1996, and NDI results through 2007. Availing this trove of data and our extensive experience working with it, as well as the full cooperation and support of the Company to study this critical problem, the following Specific Aims are proposed: Aim 1: Estimate the concentration of fine (PM2.5) and other particulate size fractions in each SEG in the workforce year by year for both PM and by chemical composition. Aim 2: In a cohort of active workers, followed historically and prospectively for up to 18 years, identify cases of CVD incidence derived from serial medical claims data, and estimate the relationship between PM2.5 exposure (both simple PM2.5 and by composition) and disease incidence utilizing selected exposure metrics- annual average each year, 95th percentile in each year, cumulative, and lagged. Aim 3: To address potential bias due to healthy worker survivor effects that can lead to underestimates of effects, apply the following approaches: extend follow-up of the cohort to mortality and model CVD mortality as end-points, rather than incidence, including inactive as well as active person-time;and applying nested structural models to estimate causal dose-response parameters for both incidence and mortality outcomes to handle time varying confounders that may also be intermediate variables on the causal pathway. PUBLIC HEALTH RELEVANCE: Millions of American workers are exposed to fine particulate in the workplaces. Although there is accumulating evidence such exposures may cause cardiovascular disease, fine particulate has not generally been measured in the workplace, nor directly regulated or uncontrolled. Thus, cardiovascular risk remains unknown. This proposal aims to provide such information in a major industrial setting with broad relevance to the US working population.