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

Abstract

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/m³ 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/m³ to 12 μg/m³ (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/m³ to 10 μg/m³ 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.

Keywords: cardiac epidemiology; clinical pharmacology; heart failure; myocardial infarction; statistics & research methods; stroke.