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 (O₃) exposure is associated with cardiovascular mortality, but little is known about the associations between O₃ and subclinical arterial disease. Objectives: We studied the longitudinal association of exposure to O₃ and progression of key subclinical arterial markers in adults: Intima-media thickness of common carotid artery (IMT_CCA), 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). IMT_CCA 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 IMT_CCA and CAC measurement, respectively. Residence-specific O₃ 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 long-term average concentrations since baseline. Linear mixed models and logistic regression model were used to evaluate relationships of long-term average exposure to O₃ with longitudinal change in IMT_CCA, CAC, and CP formation, respectively. Results: Mean progression rates of IMT_CCA and CAC were 12±0.5μm and 25±1.4  Agatston units per year 25±1.4  Agatston units per year. CP formation was identified in 55% of the subjects. A 3-ppb increase in long-term average O₃ exposure was associated with a 5.6-μm [95% confidence interval (CI): 1.4, 9.7] greater increase in IMT_CCA over 10 y. A 3-ppb increase in O₃ was also associated with new CP formation [odds ratio (OR): 1.2 (95% CI: 1.1, 1.4)] but not CAC progression [−8 Agatston units (95% CI: −18, 2)]. Associations were robust in the analysis with extended covariate adjustment, including copollutants, i.e., nitrogen oxides (NO_x) and particulate matter with diameter <2.5μm (PM_2.5). Conclusion: Over almost a decade of follow-up, outdoor O₃ concentrations were associated with increased rate of carotid wall thickness progression and risk of new plaque formation, suggesting arterial injury in this cohort.