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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number111211
JournalEnvironmental Research
Volume198
DOIs
StatePublished - Jul 2021

Keywords

  • DNA methylation
  • Heart rate variability
  • Mediation
  • Particulate matter
  • QT interval Duration

ASJC Scopus subject areas

  • Biochemistry
  • Environmental Science(all)

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