Cardiovascular Disease and Fine Particulate Matter: Lessons and Limitations of an Integrated Exposure–Response Approach

Substantial evidence indicates that long-term exposure to fine particulate matter from multiple combustion sources contributes to cardiovascular disease (CVD). An integrated exposure–response (IER) approach uses evidence from exposures to air pollution, second-hand smoke, and active cigarette smoking to explore mortality exposure–risk relationships. Although there are limitations, this approach provides a useful framework to evaluate consistency and coherency of the evidence and to estimate burden of disease from air pollution. Humans are exposed to combustion-related fine particulate matter (particles ≤2.5 µm in aerodynamic diameter), or PM2.5, from multiple sources, including ambient air pollution, household air pollution, second-hand cigarette smoke (SHS), and active smoking. There is substantial evidence that breathing combustion-derived PM2.5 from these sources contributes to CVD.1 Recently, estimators of PM2.5 relative risk (RR), termed IER functions, have been developed that integrate CVD mortality risk estimates for air pollution, SHS, and active smoking. They describe the shape of the PM2.5–CVD mortality relationship over a broad range of exposure to PM2.5.2–4 The development of IER was motivated by 2 research needs. First, the need to address the plausibility of reported CVD mortality risk estimates for air pollution and SHS relative to risk from active smoking. Exposures to PM2.5 from air pollution and SHS are extremely small compared with that from active smoking. However, moderately elevated long-term exposures to ambient PM2.5 (20 µg/m3) and comparable exposures to SHS are associated with an ≈25% to 30% increased risk of CVD mortality1,5,6—estimates much larger than expected based on proportional or linear extrapolations of the effects of active smoking. Second, there was a need to develop risk functions to estimate burden of disease attributable to ambient PM2.5 across a wide range of exposures, including …