Long-term exposure to iron and copper in fine particulate air pollution and their combined impact on reactive oxygen species concentration in lung fluid: A population-based cohort study of cardiovascular disease incidence and mortality in Toronto, Canada

Abstract

Background: Exposure to fine particulate air pollution (PM2.5) is associated with increased cardiovascular disease (CVD) morbidity and mortality but less is known about specific PM2.5 components, such as those from non-tailpipe sources, which have contributed to an important portion of primary particles. We investigated the associations of long-term exposure to iron (Fe) and copper (Cu) in PM2.5 (two metal components mainly originating from non-tailpipe emissions), and their combined impact on the concentration of reactive oxygen species (ROS) in lung fluid, with incident acute myocardial infarction (AMI), congestive heart failure (CHF) and CVD death. Methods: We conducted a population-based cohort study in Toronto, Canada. Exposures to Fe and Cu in PM2.5 and their combined impact on ROS were estimated using land use regression models. We used mixed-effects Cox regression models to examine the associations between the exposures and health outcomes. A series of sensitivity analyses were conducted, including indirect adjustment for individual-level cardiovascular risk factors (e.g. smoking), and adjustment for PM2.5 and nitrogen dioxide (NO2).Results: In single-pollutant models, we found positive associations between the three exposure measures and all three CVD outcomes, with the strongest associations detected for the estimated ROS. The associations of AMI and CHF were sensitive to indirect adjustment, but remained robust for CVD death in all other sensitivity analyses. In multi-pollutant models, the associations of the three exposures generally remained unaltered. Interestingly, adjustment for ROS did not substantially change the associations between PM2.5 and CVD, but attenuated the associations of NO2.Conclusions: Long-term exposure to Fe and Cu in PM2.5 and their combined impact on ROS were consistently associated with increased CVD death.