Abstract

ImportanceDespite biological plausibility, very few epidemiologic studies have investigated the risks of clinically significant bleeding events due to particulate air pollution. ObjectiveTo measure the independent and synergistic effects of PM2.5 exposure and anticoagulant use on serious bleeding events. DesignRetrospective cohort study (2008–2016). SettingNationwide Medicare population. ParticipantsA 50% random sample of Medicare Part D-eligible Fee-for-Service beneficiaries at high risk for cardiovascular and thromboembolic events. ExposuresFine particulate matter (PM2.5) and anticoagulant drugs (apixaban, dabigatran, edoxaban, rivaroxaban, or warfarin). Main outcomes and measuresThe outcomes were acute hospitalizations for gastrointestinal bleeding, intracranial bleeding, or epistaxis. Hazard ratios and 95% CIs for PM2.5 exposure were estimated by fitting inverse probability weighted marginal structural Cox proportional hazards models. The relative excess risk due to interaction was used to assess additive-scale interaction between PM2.5 exposure and anticoagulant use. ResultsThe study cohort included 1.86 million high-risk older adults (mean age 77, 60% male, 87% White, 8% Black, 30% anticoagulant users, mean PM2.5 exposure 8.81 μg/m3). A 10 μg/m3 increase in PM2.5 was associated with a 48% (95% CI: 45%–52%), 58% (95% CI: 49%–68%) and 55% (95% CI: 37%–76%) increased risk of gastrointestinal bleeding, intracranial bleeding, and epistaxis, respectively. Significant additive interaction between PM2.5 exposure and anticoagulant use was observed for gastrointestinal and intracranial bleeding. ConclusionsAmong older adults at high risk for cardiovascular and thromboembolic events, increasing PM2.5 exposure was significantly associated with increased risk of gastrointestinal bleeding, intracranial bleeding, and epistaxis. In addition, PM2.5 exposure and anticoagulant use may act together to increase risks of severe gastrointestinal and intracranial bleeding. Thus, clinicians may recommend that high-risk individuals limit their outdoor air pollution exposure during periods of increased PM2.5 concentrations. Our findings may inform environmental policies to protect the health of vulnerable populations.

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