Effects of air pollution on liver metabolism with relevance for cardiovascular disease: a multilevel analysis

Abstract

The liver is a possible target organ for exposure to particulate air pollution, which has been associated with acute and chronic cardiovascular effects. The studies contained within this dissertation evaluate the effects of ambient measures of PM10, NO2 and SO2 in relation to individual cholesterol parameters, LDL and HDL, in manuscript one, and alanine aminotransferase (ALT) levels in manuscript two. I employed multilevel analysis on individuals nested in counties in a nationally representative sample survey data merged with ambient air pollution monitoring data. I explored the contribution of the mean county and deviation from the mean county pollution levels to evaluate the independent contribution of aggregate and individual exposures on individual outcome parameters. In random intercepts models of LDL, a mean county average increase of 10[microgram]/dL of PM10 and 10 ppb of NO2 was associated with an increase of 4.26 mg/dL (95% CI: -1.57, 10.06) and 3.61 mg/dL (95% CI: 0.98,6.30). To the extent that individual level variation exists, the individual level pollutant estimates support the positive effect of PM10 and NO2 at the county level. Some evidence exists that the individual level effects of PM10 and SO2 are higher at higher county mean levels of air pollution. Log ALT levels are inversely related to PM10 exposure at both the county (-0.011; 95% CI: -0.040, 0.017 ) and individual level ( -0.019 95% CI: -0.032, -0.005). The data suggest that log ALT is positively associated with county-level NO2 and though negative at mean county levels, the individual-level effect is more positive at higher county levels of NO2. Though the direction of these results is not consistent with hepatotoxicity, these results suggest alterations in liver metabolism that are shared with current cigarette smoking and may signify pathological changes in the liver. These data from around the country provide exposure contrasts that are evaluated against the alterations in the outcome measures at the appropriate level in the mixed models analysis. The cholesterol study provides evidence for a link between PM and atherosclerosis. The ALT study suggests a paradoxical relationship that may point to a meaningful alteration in metabolism with relevance to atherosclerosis

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