TY - JOUR
T1 - 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
AU - Gondalia, Rahul
AU - Baldassari, Antoine
AU - Holliday, Katelyn M.
AU - Justice, Anne E.
AU - Stewart, James D.
AU - Liao, Duanping
AU - Yanosky, Jeff D.
AU - Engel, Stephanie M.
AU - Sheps, David
AU - Jordahl, Kristina M.
AU - Bhatti, Parveen
AU - Horvath, Steve
AU - Assimes, Themistocles L.
AU - Demerath, Ellen W.
AU - Guan, Weihua
AU - Fornage, Myriam
AU - Bressler, Jan
AU - North, Kari E.
AU - Conneely, Karen N.
AU - Li, Yun
AU - Hou, Lifang
AU - Baccarelli, Andrea A.
AU - Whitsel, Eric A.
N1 - Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/7
Y1 - 2021/7
N2 - 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.
AB - 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.
KW - DNA methylation
KW - Heart rate variability
KW - Mediation
KW - Particulate matter
KW - QT interval Duration
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U2 - 10.1016/j.envres.2021.111211
DO - 10.1016/j.envres.2021.111211
M3 - Article
C2 - 33895111
AN - SCOPUS:85105356270
SN - 0013-9351
VL - 198
JO - Environmental Research
JF - Environmental Research
M1 - 111211
ER -
