Air Pollution and the microvasculature: a cross-sectional assessment of in vivo retinal images in the population-based multi-ethnic study of atherosclerosis (MESA)

Abstract

Background: Long- and short-term exposures to air pollution, especially fine particulate matter (PM(2.5)), have been linked to cardiovascular morbidity and mortality. One hypothesized mechanism for these associations involves microvascular effects. Retinal photography provides a novel, in vivo approach to examine the association of air pollution with changes in the human microvasculature.

Methods and findings: Chronic and acute associations between residential air pollution concentrations and retinal vessel diameters, expressed as central retinal arteriolar equivalents (CRAE) and central retinal venular equivalents (CRVE), were examined using digital retinal images taken in Multi-Ethnic Study of Atherosclerosis (MESA) participants between 2002 and 2003. Study participants (46 to 87 years of age) were without clinical cardiovascular disease at the baseline examination (2000-2002). Long-term outdoor concentrations of PM(2.5) were estimated at each participant's home for the 2 years preceding the clinical exam using a spatio-temporal model. Short-term concentrations were assigned using outdoor measurements on the day preceding the clinical exam. Residential proximity to roadways was also used as an indicator of long-term traffic exposures. All associations were examined using linear regression models adjusted for subject-specific age, sex, race/ethnicity, education, income, smoking status, alcohol use, physical activity, body mass index, family history of cardiovascular disease, diabetes status, serum cholesterol, glucose, blood pressure, emphysema, C-reactive protein, medication use, and fellow vessel diameter. Short-term associations were further controlled for weather and seasonality. Among the 4,607 participants with complete data, CRAE were found to be narrower among persons residing in regions with increased long- and short-term levels of PM(2.5). These relationships were observed in a joint exposure model with -0.8 µm (95% confidence interval [CI] -1.1 to -0.5) and -0.4 µm (95% CI -0.8 to 0.1) decreases in CRAE per interquartile increases in long- (3 µg/m(3)) and short-term (9 µg/m(3)) PM(2.5) levels, respectively. These reductions in CRAE are equivalent to 7- and 3-year increases in age in the same cohort. Similarly, living near a major road was also associated with a -0.7 µm decrease (95% CI -1.4 to 0.1) in CRAE. Although the chronic association with CRAE was largely influenced by differences in exposure between cities, this relationship was generally robust to control for city-level covariates and no significant differences were observed between cities. Wider CRVE were associated with living in areas of higher PM(2.5) concentrations, but these findings were less robust and not supported by the presence of consistent acute associations with PM(2.5).

Conclusions: Residing in regions with higher air pollution concentrations and experiencing daily increases in air pollution were each associated with narrower retinal arteriolar diameters in older individuals. These findings support the hypothesis that important vascular phenomena are associated with small increases in short-term or long-term air pollution exposures, even at current exposure levels, and further corroborate reported associations between air pollution and the development and exacerbation of clinical cardiovascular disease. Please see later in the article for the Editors' Summary.

Figure 1. Associations between retinal arteriolar diameter (CRAE) and modeled long-term PM_2.5 concentrations after control for covariates.

Note: CRAE values represent residuals from full joint model (i.e., model controlled for age, sex, race/ethnicity, BMI, waist-to-hip ratio, income, education, smoking history, alcohol use, family history of cardiovascular disease, LDL, HDL, blood pressure, diabetes, glucose, physical activity, emphysema, CRP, fibrinogen, homocysteine, CRVE, and previous day PM_2.5 concentration). Data are plotted as a cubic polynomial with 3 df.

Figure 2. City-wide associations between CRAE and modeled long-term PM_2.5 concentrations after control for covariates.

Notes: CRAE values presented as the residuals from a model controlled for age, sex, race/ethnicity, BMI, waist-to-hip ratio, income, education, smoking history, alcohol use, family history of cardiovascular disease, LDL, HDL, blood pressure, diabetes, glucose, physical activity, emphysema, CRP, fibrinogen, homocysteine, CRVE, and previous day PM_2.5 concentration.

Figure 3. City-wide associations between CRVE and modeled long-term PM_2.5 concentrations after control for covariates.

Notes: CRVE values presented as the residuals from a model controlled for age, sex, race/ethnicity, BMI, waist-to-hip ratio, income, education, smoking history, alcohol use, family history of cardiovascular disease, LDL, HDL, blood pressure, diabetes, glucose, physical activity, emphysema, CRP, fibrinogen, homocysteine, CRAE, and previous day PM_2.5 concentration.