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Title: Epigenetically mediated electrocardiographic manifestations of sub-chronic exposures to ambient particulate matter air pollution in the Women's Health Initiative and Atherosclerosis Risk in Communities Study.

Authors: Gondalia, Rahul; Baldassari, Antoine; Holliday, Katelyn M; Justice, Anne E; Stewart, James D; Liao, Duanping; Yanosky, Jeff D; Engel, Stephanie M; Sheps, David; Jordahl, Kristina M; Bhatti, Parveen; Horvath, Steve; Assimes, Themistocles L; Demerath, Ellen W; Guan, Weihua; Fornage, Myriam; Bressler, Jan; North, Kari E; Conneely, Karen N; Li, Yun; Hou, Lifang; Baccarelli, Andrea A; Whitsel, Eric A

Published In Environ Res, (2021 Jul)

Abstract: BACKGROUND: Short-duration exposure to ambient particulate matter (PM) air pollution is associated with cardiac autonomic dysfunction and prolonged ventricular repolarization. However, associations with sub-chronic exposures to coarser particulates are relatively poorly characterized as are molecular mechanisms underlying their potential relationships with cardiovascular disease. MATERIALS AND METHODS: We estimated associations between monthly mean concentrations of PM < 10 μm and 2.5-10 μm in diameter (PM10; PM2.5-10) with time-domain measures of heart rate variability (HRV) and QT interval duration (QT) among U.S. women and men in the Women's Health Initiative and Atherosclerosis Risk in Communities Study (nHRV = 82,107; nQT = 76,711). Then we examined mediation of the PM-HRV and PM-QT associations by DNA methylation (DNAm) at three Cytosine-phosphate-Guanine (CpG) sites (cg19004594, cg24102420, cg12124767) with known sensitivity to monthly mean PM concentrations in a subset of the participants (nHRV = 7,169; nQT = 6,895). After multiply imputing missing PM, electrocardiographic and covariable data, we estimated associations using attrition-weighted, linear, mixed, longitudinal models adjusting for sociodemographic, behavioral, meteorological, and clinical characteristics. We assessed mediation by estimating the proportions of PM-HRV and PM-QT associations mediated by DNAm. RESULTS: We found little evidence of PM-HRV association, PM-QT association, or mediation by DNAm. CONCLUSIONS: The findings suggest that among racially/ethnically and environmentally diverse U.S. populations, sub-chronic exposures to coarser particulates may not exert appreciable, epigenetically mediated effects on cardiac autonomic function or ventricular repolarization. Further investigation in better-powered studies is warranted, with additional focus on shorter duration exposures to finer particulates and non-electrocardiographic outcomes among relatively susceptible populations.

PubMed ID: 33895111 Exiting the NIEHS site

MeSH Terms: Air Pollutants*/analysis; Air Pollutants*/toxicity; Air Pollution*/adverse effects; Air Pollution*/analysis; Atherosclerosis*/chemically induced; Atherosclerosis*/epidemiology; Atherosclerosis*/genetics; Environmental Exposure/adverse effects; Environmental Exposure/analysis; Female; Humans; Male; Particulate Matter/analysis; Particulate Matter/toxicity; Women's Health

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