Abstract
AIMS: Stroke is a leading cause of death and disability for Americans, and growing evidence suggests that air pollution may play an important role. To facilitate pollution control efforts, the National Academy of Sciences and the World Health Organization have prioritized determining which air pollutants are most toxic. However, evidence is limited for the simultaneous effects of multiple air pollutants on stroke. METHODS AND RESULTS: We constructed a nationwide population-based cohort study, using the Medicare Chronic Conditions Warehouse (2000-2017) and high-resolution air pollution data, to investigate the impact of long-term exposure to ambient PM(2.5), NO(2), and ground-level O(3) on incident stroke. Hazard ratios (HR) for stroke incidence were estimated using single-, bi-, and tri-pollutant Cox proportional hazards models. We identified ~2.2 million incident stroke cases among 17,443,900 fee-for-service Medicare beneficiaries. Per interquartile range (IQR) increase in the annual average PM(2.5) (3.7 μg/m(3)), NO(2) (12.4 ppb), and warm-season O(3) (6.5 ppb) one-year prior to diagnosis, the HRs were 1.022 (95% CI: 1.017-1.028), 1.060 (95% CI: 1.054-1.065), and 1.021 (95% CI: 1.017-1.024), respectively, from the tri-pollutant model. There was strong evidence of linearity in concentration-response relationships for all three air pollutants in single-pollutant models. This linear relationship remained robust for NO(2) and O(3) in tri-pollutant models while the effect of PM(2.5) attenuated at the lower end of concentrations. CONCLUSION: Using a large nationwide cohort, our study suggests that long-term exposure to PM(2.5), NO(2), and O(3) may independently increase the risk of stroke among the US elderly, among which traffic-related air pollution plays a particularly crucial role.