Exposure to Fine Particulate Matter and Incidence of Coronary Events: The Mediation Effect by Atherosclerotic Progression

Abstract

Background/Aim: Epidemiological evidence on the mechanisms for association between long-term exposure to fine particulate matters (PM2.5) and coronary events is limited. We investigated the role of atherosclerotic progression, as potential mediator, in the association between PM2.5 and incidence of coronary events. Methods: In a study of 294 Chinese patients with stable angina, we repeatedly measured coronary plaque phenotypes on computed tomography angiography, including coronary artery calcium (CAC), total, calcified and non-calcified plaque volumes between 2009 and 2014 and followed their incident events until 2016. Annual average PM2.5 concentrations were estimated by a satellite-based exposure model and were aggregated to the year of the follow-up exam and the incident events at the participants’ home. We conducted Cox analysis to estimate effect of PM2.5 exposure on incident events and used mixed effect model to assess relationships between PM2.5 and progression of atherosclerosis. Mediation analysis was applied to evaluate mediated effects by the atherosclerotic markers. Results: Patients were on average 53 year’s old with 15% experienced incident events. CAC increased by 20.3±3.5 Agataton units per year, and total plaque volumes by 28.0±8.9 mm3 per year. For each 20 PM2.5 μg/m3 increase, CAC progressed by 7.7 Agataton units per year (95%CI: 2.3-13.2) and total plaque volumes increased by 20.3 mm3 per year (1.7-39.0), adjusting for risk factors. Using mediation analysis, we observed a positive direct effect of PM2.5 on incidence of coronary events (HR=1.20, 95%CI: 1.08-1.32) and an indirect effect mediated by increased total plaque volumes (HR=1.06, 95%CI: 1.01-1.13) accounting for 25.5% of the total effect. The proportion mediated through CAC progression accounting for 18.8%. No associations were observed between PM2.5 and other plaque phenotypes. Conclusion: This study provided insight of evidence on the role of atherosclerotic progression in association between ambient PM2.5 and coronary events in a susceptible population.