摘要：Background: Long-term ozone ( O 3 ) exposure is associated with cardiovascular mortality, but little is known about the associations between O 3 and subclinical arterial disease. Objectives: We studied the longitudinal association of exposure to O 3 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 O 3 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 O 3 with longitudinal change in IMT CCA , CAC, and CP formation, respectively. Results: Mean progression rates of IMT CCA and CAC were 12 ± 0.5 μ 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 - μ m [95% confidence interval (CI): 1.4, 9.7] greater increase in IMT CCA over 10 y. A 3 -ppb increase in O 3 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 < 2.5 μ m ( PM 2.5 ). 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.
