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

Sara Adar and colleagues show that residing in locations with higher air pollution concentrations and experiencing daily increases in air pollution are associated with narrower retinal arteriolar diameters in older individuals, thus providing a link between air pollution and cardiovascular disease.

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

Editors' Summary

Background

Cardiovascular disease (CVD)—disease that affects the heart and/or the blood vessels—is a common cause of illness and death among adults in developed countries. In the United States, for example, the leading cause of death is coronary heart disease, a CVD in which narrowing of the heart's arteries by atherosclerotic plaques (fatty deposits that build up with age) slows the blood supply to the heart and may eventually cause a heart attack (myocardial infarction). Other types of CVD include stroke (in which atherosclerotic plaques interrupt the brain's blood supply) and peripheral arterial disease (in which the blood supply to the limbs is blocked). Smoking, high blood pressure, high blood levels of cholesterol (a type of fat), having diabetes, being overweight, and being physically inactive all increase a person's risk of developing CVD. Treatments for CVD include lifestyle changes and taking drugs that lower blood pressure or blood cholesterol levels.

Why Was This Study Done?

Another risk factor for CVD is exposure to long-term and/or short-term air pollution. Fine particle pollution or PM _2.5 is particularly strongly associated with an increased risk of CVD. PM _2.5—particulate matter 2.5 µm in diameter or 1/30th the diameter of a human hair—is mainly produced by motor vehicles, power plants, and other combustion sources. Why PM _2.5 increases CVD risk is not clear but one possibility is that it alters the body's microvasculature (fine blood vessels known as capillaries, arterioles, and venules), thereby impairing the blood flow through the heart and brain. In this study, the researchers use noninvasive digital retinal photography to investigate whether there is an association between air pollution and changes in the human microvasculature. The retina—a light-sensitive layer at the back of the eye that converts images into electrical messages and sends them to the brain—has a dense microvasculature. Retinal photography is used to check the retinal microvasculature for signs of potentially blinding eye diseases such as diabetic retinopathy. Previous studies have found that narrower than normal retinal arterioles and wider than normal retinal venules are associated with CVD.

What Did the Researchers Do and Find?

The researchers used digital retinal photography to measure the diameters of retinal blood vessels in the participants of the Multi-Ethnic Study of Atherosclerosis (MESA). This study is investigating CVD progression in people aged 45–84 years of various ethnic backgrounds who had no CVD symptoms when they enrolled in the study in 2000–2002. The researchers modeled the long-term outdoor concentration of PM _2.5 at each participant's house for the 2-year period preceding the retinal examination (which was done between 2002 and 2003) using data on PM _2.5 levels collected by regulatory monitoring stations as well as study-specific air samples collected outside of the homes and in the communities of study participants. Outdoor PM _2.5 measurements taken the day before the examination provided short-term PM _2.5 levels. Among the 4,607 MESA participants who had complete data, retinal arteriolar diameters were narrowed among those who lived in regions with increased long- and short-term PM _2.5 levels. Specifically, an increase in long-term PM _2.5 concentrations of 3 µg/m ³ was associated with a 0.8 µm decrease in arteriolar diameter, a reduction equivalent to that seen for a 7-year increase in age in this group of people. Living near a major road, another indicator of long-term exposure to PM _2.5 pollution, was also associated with narrowed arterioles. Finally, increased retinal venular diameters were weakly associated with long-term high PM _2.5 concentrations.

What Do These Findings Mean?

These findings indicate that living in areas with long-term air pollution or being exposed to short-term air pollution is associated with narrowing of the retinal arterioles in older individuals. They also show that widening of retinal venules is associated with long-term (but not short-term) PM _2.5 pollution. Together, these findings support the hypothesis that long- and short-term air pollution increases CVD risk through effects on the microvasculature. However, they do not prove that PM _2.5 is the constituent of air pollution that drives microvascular changes—these findings could reflect the toxicity of another pollutant or the pollution mixture as a whole. Importantly, these findings show that microvascular changes can occur at the PM _2.5 levels that commonly occur in developed countries, which are well below those seen in developing countries. Worryingly, they also suggest that the deleterious cardiovascular effects of air pollution could occur at levels below existing regulatory standards.

Additional Information

Please access these Web sites via the online version of this summary at http://dx.doi.org/ 10.1371/journal.pmed.1000372.

• The American Heart Association provides information for patients and caregivers on all aspects of cardiovascular disease (in several languages), including information on air pollution, heart disease, and stroke

• The US Centers for Disease Control and Prevention has information on heart disease and on stroke

• Information is available from the British Heart Foundation on cardiovascular disease

• The UK National Health Service Choices website provides information for patients and caregivers about cardiovascular disease

• MedlinePlus provides links to other sources of information on heart disease and on vascular disease (in English and Spanish)

• The AIRNow site provides information about US air quality and about air pollution and health

• The Air Quality Archive has up-to-date information about air pollution in the UK and information about the health effects of air pollution

• The US Environmental Protection Agency has information on PM2.5

• The following Web sites contain information available on the MESA and MESA Air studies