Air Pollution and High Density Lipoprotein Structure and Function

Thesis (Ph.D.)--University of Washington, 2016-06

BACKGROUND: A growing body of evidence suggests that air pollution is an important contributor to risk of cardiovascular disease. Federal regulatory agencies require evidence of the biological mechanisms explaining the relationship between air pollution and cardiovascular disease in order to inform regulatory policy. High density lipoproteins (HDL) are an important cardiovascular risk factor, and air pollution induced changes in HDL may explain some of this relationship. We examined the relationship between air pollution and HDL in a suite of complementary studies. METHODS: We first examined the cross-sectional relationship between air pollution and both HDL cholesterol (HDL-C) and HDL particle number (HDL-P) in the Multi-Ethnic Study of Atherosclerosis Air Pollution study (MESA Air), an ethnically diverse cohort of community-dwelling adults. We also examined whether HDL mediated the longitudinal relationship between air pollution and coronary artery calcium (CAC) in MESA. We estimated individual residential ambient fine particulate pollution exposure (PM2.5) and black carbon (BC) concentrations using a fine-scale likelihood-based spatiotemporal model and cohort-specific monitoring. HDL-C and HDL-P were measured using the cholesterol oxidase method and nuclear magnetic resonance spectroscopy, respectively. CAC was measured at multiple exams using computed tomographic imaging with a standardized method. We used multivariable linear regression and linear mixed models to examine the relationship between air pollution exposure, HDL measures, and CAC outcomes. We also examined the relationship between controlled exposure to air pollution in an experimental setting, using a double-blind crossover design randomized by order of intervention/control status. Diesel-powered motor vehicles are a major source of urban PM2.5, and we use well-characterized and tightly controlled diesel exhaust (DE) inhalation as a model of traffic-related air pollution exposure. We examined the effect of traffic-related air pollutants on anti-oxidant function of HDL, on paraoxonase-1 (PON1) activity, and on changes in the HDL proteome. Outcomes were measured before and after exposure to either DE or filtered air and changes in HDL outcomes were examined using linear mixed models. RESULTS: In our cross-sectional study, a 0.7 10-6m-1 higher exposure to black carbon (a marker of traffic-related pollution) averaged over a one-year period was associated with a lower HDL-C. In the three month averaging time period, a 5 µg/m3 higher PM2.5 was associated with lower HDL-P, but not HDL-C. In our controlled experimental study, we did not find evidence that exposure to DE was associated with changes in HDL function or measured characteristics. We did not find that HDL mediated the longitudinal relationship between air pollution and CAC. We did, however, find that an averaged one year 5 µg/m3 higher PM2.5 was associated with lower annual change in HDL-C. CONCLUSIONS: These data are consistent with the hypothesis that exposure to ambient air pollution is adversely associated with measures of HDL. Our study used state of the art measurement of air pollution combined with novel measures of HDL to produce new evidence supporting the relationship between air pollution and cardiovascular disease. Future study is needed to explain how these changes occur and if chronic exposure to air pollution may be associated with changes in HDL function over time.