Interaction between Long-Term Exposure to Fine Particulate Matter and Physical Activity, and Risk of Cardiovascular Disease and Overall Mortality in U.S. Women

BACKGROUND: Increased respiration during physical activity may increase air pollution dose, which may attenuate the benefits of physical activity on cardiovascular disease (CVD) risk and overall mortality. OBJECTIVES: We aimed to examine the multiplicative interaction between long-term ambient residential exposure to fine particulate matter [Formula: see text] ([Formula: see text]) and physical activity in the association with CVD risk and overall mortality. METHODS: We followed 104,990 female participants of the U.S.-based prospective Nurses’ Health Study from 1988 to 2008. We used Cox proportional hazards models to assess the independent associations of 24-months moving average residential [Formula: see text] exposure and physical activity updated every 4 y and the multiplicative interaction of the two on CVD (myocardial infarction and stroke) risk and overall mortality, after adjusting for demographics and CVD risk factors. RESULTS: During 20 years of follow-up, we documented 6,074 incident CVD cases and 9,827 deaths. In fully adjusted models, [Formula: see text] exposure was associated with modest increased risks of CVD [hazard ratio (HR) for fifth quintile [Formula: see text] compared to first quintile [Formula: see text]: 1.09, 95% confidence interval (CI): 0.99, 1.20; [Formula: see text]] and overall mortality (HR fifth compared to first quintile: 1.10, 95% CI: 1.02, 1.19; [Formula: see text]). Higher overall physical activity was associated with substantially lower risk of CVD [HR fourth quartile, which was [Formula: see text] equivalent of task (MET)-h/wk, compared to first quartile ([Formula: see text]): 0.61, 95% CI: 0.57, 0.66; [Formula: see text]] and overall mortality (HR fourth compared to first quartile: 0.40, 95% CI: 0.37, 0.42; [Formula: see text]). We observed no statistically significant interactions between [Formula: see text] exposure and physical activity (overall, walking, vigorous activity) in association with CVD risk and overall mortality. DISCUSSION: In this study of U.S. women, we observed no multiplicative interaction between long-term [Formula: see text] exposure and physical activity; higher physical activity was strongly associated with lower CVD risk and overall mortality at all levels of [Formula: see text] exposure. https://doi.org/10.1289/EHP7402