Particulate Air Pollution and Carotid Artery Stenosis

Outdoor fine particulate air pollution (mass concentration of particles <2.5 μm in diameter [PM_2.5]) exposure is ubiquitous and is associated with cardiovascular mortality and ischemic heart disease events (1). PM_2.5 exposure also increases the risk for ischemic stroke (2). The vascular and hemodynamic effects of PM_2.5 may explain some, but not all, of this increased risk (2). However, it is unknown whether PM_2.5 is associated with prevalent clinical atherosclerosis, such as carotid artery stenosis (CAS), a lesion critical to the pathophysiology of ischemic stroke (3). To achieve this objective, we examined PM_2.5 and prevalent CAS among more than 300,000 residents of New York, New Jersey, and Connecticut.

We selected tristate residents age 40 to 80 years participating in Life Line Vascular Screening (LLS, Independence, Ohio) without previous procedures for carotid disease (N = 307,444). The cohort consisted primarily of individuals who self-paid for vascular screening tests from 2003 to 2008 in the tristate region (4), This region was chosen because of its large, heterogeneous population and wide variation in PM_2.5 exposure (6.7 to 14.7 μg/m³). Prior to vascular ultrasound, participants completed demographic, smoking, medical comorbidity, cardiovascular risk factor, and family history questionnaires (4). CAS was assessed with bilateral carotid artery duplex ultrasound. Maximal peak systolic and end diastolic velocity in the right and left internal carotid arteries (ICA) were recorded. CAS was defined as stenosis ≥50% in either ICA (or both ICAs) by duplex ultrasound (ICA peak systolic velocity ≥125 cm/s) (3,5). Each participant’s average PM_2.5 exposures were estimated by zip code empirical Bayesian kriging of ambient monitoring data from the Environmental Protection Agency’s Air Quality System. PM_2.5 exposures from years 2003 to 2008 were selected for analysis due to completeness of Life Line cohort screening data. Baseline characteristics and CAS prevalence by PM_2.5 quartiles were examined. Multivariable logistic regression models, sequentially adjusting for age, demographics, medical history, and zip code median household income, were used to estimate the risk of CAS per 10 μg/m³ increase in PM_2.5. Additional multivariable logistic regression by quartiles and medians of PM_2.5 exposure on risk of CAS was performed. Sensitivity analyses of moderate and severe CAS were also conducted.

Compared with other quartiles of PM_2.5 exposure, participants in quartile 4 (12.9 to 14.7 μg/m³) were younger, and were less likely to be white, have hypertension, have hyperlipidemia, or exercise regularly; however, they were more likely to have diabetes mellitus (p < 0.001 for all). In a logistic regression model adjusting for age, sex, race/ethnicity, body mass index, high cholesterol, hypertension, physical activity, family history of cardiovascular disease, household income, and smoking behaviors, we found a nearly 2-fold increase in CAS (odds ratio [OR]: 1.90, 95% confidence interval [CI]: 1.35 to 2.66) for every 10-μg/m³ increase in PM_2.5. The odds of CAS increased when the highest versus lowest quartile of PM_2.5 and above and below the median PM_2.5 were compared (ORs: 1.24, 95% CI: 1.11 to 1.37; and 1.12, 95% CI: 1.04 to 1.21, respectively) (Figure 1). Results were similar by sex and race. The association between a 10-μg/m³ increase in PM_2.5 and CAS was consistent when restricted to patients with moderate (OR: 1.9, 95% CI: 1.31 to 2.72) and severe (OR: 1.79, 95% CI: 1.05 to 3.07) CAS.

FIGURE 1. Adjusted Odds Ratio for Carotid Artery Stenosis by PM_2.5 exposure.

Odds ratios adjusted for age, sex, race/ethnicity, body mass index, dyslipidemia, hypertension, diabetes, physical activity (yes/no), family history of cardiovascular disease, socioeconomic status, and smoking. PM_2.5 = the mass concentration of particles <2.5 μm in aerodynamic diameter; Q = quartile.

Our study demonstrates for the first time that PM_2.5 is independently associated with CAS, an important risk factor for cerebrovascular disease and stroke. These results support the relationship between fine particle air pollution and prevalent atherosclerosis, and may suggest a pathway through which PM_2.5 increases cardiovascular risk. Strengths of this study include the large sample size, validated CAS measurements, wide age range, and availability of lifestyle, medical, and household income data. Limitations include the lack of complete temporal data on PM_2.5 exposure and clinical outcomes for CAS. Our assessments of cardiovascular risk factors were limited to self-report, and we lacked data on medical therapy that could modify the relationship of PM_2.5 exposure to CAS. As this is a cross-sectional study, we cannot rule out exposure misclassification or the effect of copollutants on the observed PM_2.5 to CAS relationship. Future studies should include source- and component-specific analyses of PM_2.5 exposure to determine which PM_2.5 fractions are most strongly associated with the observed increases in cerebrovascular disease and CAS.