Effects of PM2.5 and Corticosteroid Use on Cardiovascular and Thromboembolic Events Among Older Adults: Evidence of Drug-Environment Interaction

Background: Exposure to fine particulate matter (PM2.5) and use of corticosteroids have both been linked to increased risk of cardiovascular/thromboembolic events (CTEs). However, no studies have assessed both PM2.5 and corticosteroid use concomitantly, nor has the potential interaction between these two risk factors been examined. Objective: To assess the existence of a synergistic effect between PM2.5 and corticosteroid use on adverse outcomes in older adults who are at high risk for CTEs. Methods: We collected a ~50% random sample of Medicare fee-for-service participants receiving care between 2008-2016 who are at high-risk for future CTE events. We followed participants until death and/or the first instance of various cardiovascular events. From a marginal structural proportional hazards model, we tested for the presence of synergy between PM2.5 and corticosteroid use on the additive scale by estimating the relative excess risk due to interaction (RERI). Outcomes included incidences of myocardial infarction or an acute coronary syndrome, ischemic stroke or transient ischemic attack, heart failure, venous thromboembolism, atrial fibrillation, and all-cause mortality. Results: Among 1,936,786 high-risk older adults (mean age 76.8, 40.0% male, 87.4% White), the mean PM2.5 exposure level was 8.3 +/- 2.4 mcg/m3 and 37.7% had at least one prescription for a systemic corticosteroid during follow-up. We observed positive relationships between PM2.5 and CTE, and between corticosteroid use and CTE. We also observed evidence of an interaction existing between corticosteroid use and PM2.5 for some CTEs. By increasing the average PM2.5 from 8 mcg/m3 to 12 mcg/m3, the RERI of corticosteroid use and PM2.5 was significant for heart failure (18.2%, 95% CI: 7.5%-29.0%), and death (8.9%, 95% CI: 1.6%-16.1%), Increasing the average PM2.5 from 5 mcg/m3 to 10 mcg/m3 yielded significant RERIs for incidences of heart failure (40.6%; 95% CI: 24.8%-56.4%) and acute coronary syndromes (31.8%; 95% CI: 10.3%-53.4%). Discussion: PM2.5 and systemic corticosteroid use were independently associated with increases in CTE hospitalizations, with evidence of significant interactions between the two exposures for heart failure, acute coronary syndromes, and death.