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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.

TitleEpigenetically 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.
Publication TypeJournal Article
Year of Publication2021
AuthorsGondalia R, Baldassari A, Holliday KM, Justice AE, Stewart JD, Liao D, Yanosky JD, Engel SM, Sheps D, Jordahl KM, Bhatti P, Horvath S, Assimes TL, Demerath EW, Guan W, Fornage M, Bressler J, North KE, Conneely KN, Li Y, Hou L, Baccarelli AA, Whitsel EA
JournalEnviron Res
Volume198
Pagination111211
Date Published2021 07
ISSN1096-0953
KeywordsAir Pollutants, Air Pollution, Atherosclerosis, Environmental Exposure, Female, Humans, Male, Particulate Matter, Women's Health
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 (PM PM) 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 = 82,107; n = 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 = 7,169; n = 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.

DOI10.1016/j.envres.2021.111211
Alternate JournalEnviron Res
PubMed ID33895111
PubMed Central IDPMC8179344
Grant ListRC2 HL102419 / HL / NHLBI NIH HHS / United States
R01 ES020836 / ES / NIEHS NIH HHS / United States
HHSN268201100004I / HL / NHLBI NIH HHS / United States
R01 NS087541 / NS / NINDS NIH HHS / United States
R25 CA094880 / CA / NCI NIH HHS / United States
HHSN268201100003C / WH / WHI NIH HHS / United States
HHSN268201700002C / HL / NHLBI NIH HHS / United States
HHSN268201700001I / HL / NHLBI NIH HHS / United States
HHSN268201100002C / WH / WHI NIH HHS / United States
T32 HL007055 / HL / NHLBI NIH HHS / United States
HHSN268201100004C / WH / WHI NIH HHS / United States
HHSN268201100001I / HL / NHLBI NIH HHS / United States
K99 HL130580 / HL / NHLBI NIH HHS / United States
T32 ES007018 / ES / NIEHS NIH HHS / United States
R01 ES017794 / ES / NIEHS NIH HHS / United States
HHSN268201100046C / HL / NHLBI NIH HHS / United States
R00 HL130580 / HL / NHLBI NIH HHS / United States
HHSN271201100004C / AG / NIA NIH HHS / United States
HHSN268201700004I / HL / NHLBI NIH HHS / United States
HHSN268201700005C / HL / NHLBI NIH HHS / United States
HHSN268201700001C / HL / NHLBI NIH HHS / United States
HHSN268201700003C / HL / NHLBI NIH HHS / United States
HHSN268201700004C / HL / NHLBI NIH HHS / United States
/ WT_ / Wellcome Trust / United Kingdom
HHSN268201100003I / HL / NHLBI NIH HHS / United States
HHSN268201100002I / HL / NHLBI NIH HHS / United States
HHSN268201300006C / HL / NHLBI NIH HHS / United States
HHSN268201700002I / HL / NHLBI NIH HHS / United States
HHSN268201700005I / HL / NHLBI NIH HHS / United States
HHSN268201700003I / HL / NHLBI NIH HHS / United States
HHSN268201100001C / WH / WHI NIH HHS / United States