Long-Term Exposure to Ambient Ozone and Progression of Subclinical Arterial Disease: The Multi-Ethnic Study of Atherosclerosis and Air Pollution

BACKGROUND: Long-term ozone (O-3) exposure is associated with cardiovascular mortality, but little is known about the associations between 03 and subclinical arterial disease. OBJECTIVES: We studied the longitudinal association of exposure to 03 and progression of key subclinical arterial markers in adults intima-media thickness of common carotid artery (IMTCCA), carotid plaque, (CP) burden, and coronary artery calcification (CAC). METHODS: CAC was measured one to four times at baseline and at follow-up exams (1999-2012) by computed tomography (CT) in 6,619 healthy adults, recruited at age 45-84 y without cardiovascular disease (CVD), over a mean of 6.5 y (standard deviation: 3.5 y). IMTCCA and CP burden were quantified in 3,392 participants using carotid artery ultrasound imaging acquired over a mean of 9 y (1.7 y). Over 91% and 89% participants had at least one follow-up IMTCCA and CAC measurement, respectively. Residence-specific 03 concentrations were estimated by a validated spatiotemporal model spanning from 1999 to 2012. This model relied on comprehensive monitoring data and geographical variables to predict individualized longterm average concentrations since baseline. Linear mixed models and logistic regression model were used to evaluate relationships of long-term average exposure to O-3 with longitudinal change in IMTCCA, CAC, and CP formation, respectively. RESULTS: Mean progression rates of IMTCCA and CAC were 12 +/- 0.5 mu m and 25 1.4 Agatston units per year. CP formation was identified in 55% of the subjects. A 3-ppb increase in long-term average O-3 exposure was associated with a 5.6-mu m [95% confidence interval (Cl): 1.4, 9.7] greater increase in IMTCCA over 10 y. A 3-ppb increase in O-3 was also associated with new CP formation [odds ratio (OR): 1.2 (95% Cl: 1.1, 1.4)] but not CAC progression [-8 Agatston units (95% Cl: -18, 2)]. Associations were robust in the analysis with extended covariate adjustment, including copollutants, i.e., nitrogen oxides (NOx) and particulate matter with diameter <2.5 mu m (PM2.5). CONCLUSION: Over almost a decade of follow-up, outdoor O-3 concentrations were associated with increased rate of carotid wall thickness progression and risk of new plaque, formation, suggesting arterial injury in this cohort.