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

Research output: Contribution to journalArticlepeer-review


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 (PM 10; PM 2.5-10) 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 (n HRV = 82,107; n QT = 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 (n HRV = 7,169; n QT = 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
StatePublished - Jul 2021

Bibliographical note

Funding Information:
The Atherosclerosis Risk in Communities study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute (NHLBI) , National Institutes of Health , Department of Health and Human Services (contract numbers HHSN268201700001I , HHSN268201700002I , HHSN268201700003I , HHSN268201700004I and HHSN268201700005I ). The authors thank the staff and participants of the ARIC study for their important contributions. Funding was also supported by 5RC2HL102419 and R01NS087541 .

Funding Information:
This work was supported by National Institute of Environmental Health Sciences ( NIEHS) grant R01-ES020836 (LH, AB, EAW), NHLBI contract HHSN268201100046C (KC), NIEHS grant R01-ES017794 (EAW), NHLBI National Research Service Award T32-HL007055 (RG), NIEHS National Research Service Award T32-ES007018 (KH), and NCI grant R25-CA094880 (KJ) .

Funding Information:
The WHI program is funded by the NHLBI , U.S. Department of Health and Human Services, through contracts HHSN268201100046C , HHSN268201100001C , HHSN268201100002C , HHSN268201100003C , HHSN268201100004C , and HHSN271201100004C . WHI-AS311 was supported by American Cancer Society award 125299-RSG-13-100-01-CCE . WHI-BAA23 was supported by NHLBI's Broad Agency Announcement contract HHSN268201300006C . WHI-MIMS was supported by Glaxo Wellcome (now GlaxoSmithKline ). All contributors to WHI science are listed at https://www.whi.org/researchers/Documents%20%20Write%20a%20Paper/WHI%20Investigator%20Long%20List.pdf .

Publisher Copyright:
© 2021 Elsevier Inc.


  • DNA methylation
  • Heart rate variability
  • Mediation
  • Particulate matter
  • QT interval Duration
  • Women's Health
  • Humans
  • Male
  • Air Pollution/adverse effects
  • Air Pollutants/analysis
  • Female
  • Particulate Matter/analysis
  • Environmental Exposure/adverse effects
  • Atherosclerosis/chemically induced

PubMed: MeSH publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Journal Article
  • Research Support, N.I.H., Extramural


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