Retrospective cohort study investigating synergism of air pollution and corticosteroid exposure in promoting cardiovascular and thromboembolic events in older adults

OBJECTIVE: To evaluate the synergistic effects created by fine particulate matter (PM(2.5)) and corticosteroid use on hospitalisation and mortality in older adults at high risk for cardiovascular thromboembolic events (CTEs). DESIGN AND SETTING: A retrospective cohort study using a US nationwide administrative healthcare claims database. PARTICIPANTS: A 50% random sample of participants with high-risk conditions for CTE from the 2008–2016 Medicare Fee-for-Service population. EXPOSURES: Corticosteroid therapy and seasonal-average PM(2.5). MAIN OUTCOME MEASURES: Incidences of myocardial infarction or acute coronary syndrome (MI/ACS), ischaemic stroke or transient ischaemic attack, heart failure (HF), venous thromboembolism, atrial fibrillation and all-cause mortality. We assessed additive interactions between PM(2.5) and corticosteroids using estimates of the relative excess risk due to interaction (RERI) obtained using marginal structural models for causal inference. RESULTS: Among the 1 936 786 individuals in the high CTE risk cohort (mean age 76.8, 40.0% male, 87.4% white), the mean PM(2.5) exposure level was 8.3±2.4 µg/m(3) and 37.7% had at least one prescription for a systemic corticosteroid during follow-up. For all outcomes, we observed increases in risk associated with corticosteroid use and with increasing PM(2.5) exposure. PM(2.5) demonstrated a non-linear relationship with some outcomes. We also observed evidence of an interaction existing between corticosteroid use and PM(2.5) for some CTEs. For an increase in PM(2.5) from 8 μg/m(3) to 12 μg/m(3) (a policy-relevant change), the RERI of corticosteroid use and PM(2.5) was significant for HF (15.6%, 95% CI 4.0%, 27.3%). Increasing PM(2.5) from 5 μg/m(3) to 10 μg/m(3) yielded significant RERIs for incidences of HF (32.4; 95% CI 14.9%, 49.9%) and MI/ACSs (29.8%; 95% CI 5.5%, 54.0%). CONCLUSION: PM(2.5) and systemic corticosteroid use were independently associated with increases in CTE hospitalisations. We also found evidence of significant additive interactions between the two exposures for HF and MI/ACSs suggesting synergy between these two exposures.