Short-term exposure to air pollution and novel markers of cardiovascular effect: a repeated measures study in the Multi-Ethnic Study of Atherosclerosis (MESA)

Abstract

Background: Several pathophysiologic mechanisms have been proposed to underlie the associations between ambient air pollutants and cardiovascular disease. We employed a repeated measures design to investigate the short-term associations of outdoor concentrations of four air pollutants – particulate matter smaller than 2.5 micrometers in diameter (PM2.5), nitrogen dioxide (NO2), ozone (O3) and sulfur dioxide (SO2) – with two blood markers involved in vascular effects of oxidative stress, soluble lectin-like oxidized LDL receptor-1 (sLOX-1) and nitrite, using data from the MESA study.Methods: 740 participants who submitted blood samples at three MESA exams between 2002 and 2007 were included. sLOX-1 and nitrite were measured in plasma samples. Daily concentrations of PM2.5, NO2, O3 and SO2 0-7 days prior to blood draw at each exam were estimated from central monitors in the six MESA regions, pre-adjusted using splines of meteorology, indicators for day of the week, and splines of site-specific time trend. Unconstrained distributed lag linear mixed effect models and generalized estimating equations were used to estimate net effects over several days with adjustment for demographic, socioeconomic and behavioral factors.Results: Median detectable nitrite and sLOX-1 concentrations were 24.7 umol/L and 94.5 pg/ml, respectively. Higher short-term PM2.5 concentrations, but not other pollutants, were associated with elevated sLOX-1 level analyzed both as a continuous outcome (percent change per interquartile increase: 18.5%, 95%CI: 2.4-37.2%) and dichotomized at the median (odds ratio per interquartile increase: 1.21, 95%CI: 1.01-1.44); the finding was not meaningfully changed after adjustment for additional covariates or in several sensitivity analyses. Pollutant concentrations were not associated with nitrite levels. Conclusion: This study adds to the evidence that short-term PM2.5 exposure is associated with higher sLOX-1 and supports the mechanistic hypothesis that oxidative modification of endogenous phospholipids in the lung by PM2.5 drives vascular endothelial cell activation via cell surface pattern recognition receptors.