(SLB-045) Mortality associated to concomitant exposure to corticosteroids and fine particulate matter: an exploratory study in older adults in Rome, Italy

Background: Recently, pharmacoepidemiologic studies aim to investigate the interplay between drug use and environmental factors on health. Adverse cardiovascular and thromboembolic events (CTEs) have been shown to be associated to high levels of fine particulate matter (PM2.5) and oral corticosteroid use independently. Evidence about the synergistic effects of these two exposures is limited.

Objectives: The present abstract represents a pilot study to explore independent and interactive effects of exposure to PM2.5 and oral corticosteroid use on mortality in older adults in Rome, Italy, with the final aim to further develop methods and include CTE outcomes.

Methods: A cohort of residents in Rome (Italy) aged 65+ at high risk for CTE, retrieved from hospital data at baseline (January 31st, 2013), was built using regional health databases. Individual follow-up times were split into trimesters, with follow-up ending at death, emigration, censoring, or study end (December 31st, 2019). Individual PM2.5 exposure at residence was estimated using spatiotemporal models (1 km × 1 km resolution) and assigned to each trimester during follow-up. Corticosteroid use was assessed through prescription claims. Time-varying cox models were used to evaluate associations with mortality, focusing on single-, bi-exposure, interaction, and stratified models. Estimates were adjusted for sex, age, birthplace, marital status, education, citizenship, and census block-level socioeconomic status at baseline.

Results: We enrolled 33,079 elderly (mean age: 77.1 years, 47.1% female). During 7 years of observation, 16,466 deaths (49.8%) were recorded, with mean follow-up of 4.9 years. The most prevalent comorbidities were cancer (45.2%), atrial fibrillation (24.3%), heart failure (16.5%), and ischemic stroke (15.1%). On average, mean PM2.5 exposure declined from 24.1 µg/m³ in the first trimester to 14.9 µg/m³ in the last one. Overall, 56% of the cohort had at least one corticosteroid prescription, with trimester-specific prevalence ranging from 7.5% to 11.8%. 23% of deaths occurred in persons using corticosteroids, and 4.5% in those exposed to PM2.5 levels above 25 µg/m³ during the event trimester. Cox models indicated a significant association between corticosteroid use and mortality (HR: 2.89, 95%CI: 2.78-2.99), while PM2.5 exposure did not increase the risk (HR: 0.997, 95%CI: 0.994-1.001 per 1 μg/m³ increment), consistently across models.

Conclusions: The present analysis proves feasibility of multivariate analyses to investigate the synergistic effects of particulate matter and corticosteroids on mortality in the Rome cohort. In the next steps analyses will be refined and CTE considered as an outcome.