Rahul Gondalia1, Antoine Baldassari2, Katelyn M Holliday3, Anne E Justice4, James D Stewart2, Duanping Liao5, Jeff D Yanosky5, Stephanie M Engel2, David Sheps6, Kristina M Jordahl7, Parveen Bhatti7, Steve Horvath8, Themistocles L Assimes9, Ellen W Demerath10, Weihua Guan11, Myriam Fornage12, Jan Bressler13, Kari E North14, Karen N Conneely15, Yun Li16, Lifang Hou17, Andrea A Baccarelli18, Eric A Whitsel19. 1. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA. Electronic address: rahgonda@unc.edu. 2. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA. 3. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA; Department of Community and Family Medicine, Duke University School of Medicine, Durham, NC, USA. 4. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA; Geisinger Health System, Danville, PA, USA. 5. Division of Epidemiology, Department of Public Health Sciences, Pennsylvania State University College of Medicine, Hershey, PA, USA. 6. Department of Epidemiology, University of Florida, Gainesville, FL, USA. 7. Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA. 8. Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; Biostatistics, School of Public Health, University of California Los Angeles, Los Angeles, USA. 9. Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA. 10. Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, USA. 11. Division of Biostatistics, University of Minnesota, Minneapolis, MN, USA. 12. Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA. 13. Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA. 14. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA; Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, NC, USA. 15. Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA. 16. Department of Genetics, University of North Carolina, Chapel Hill, NC, USA; Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA; Department of Computer Science, University of North Carolina, Chapel Hill, NC, USA. 17. Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University Chicago, Evanston, IL, USA; Center for Population Epigenetics, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. 18. Laboratory of Environmental Epigenetics, Departments of Environmental Health Sciences and Epidemiology, Columbia University Mailman School of Public Health, New York, NY, USA. 19. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA; Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
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.
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.
Authors: Javier Barallobre-Barreiro; Athanasios Didangelos; Friedrich A Schoendube; Ignat Drozdov; Xiaoke Yin; Mariana Fernández-Caggiano; Peter Willeit; Valentina O Puntmann; Guillermo Aldama-López; Ajay M Shah; Nieves Doménech; Manuel Mayr Journal: Circulation Date: 2012-01-18 Impact factor: 29.690
Authors: Douglas W Dockery; Heike Luttmann-Gibson; David Q Rich; Mark S Link; Murray A Mittleman; Diane R Gold; Petros Koutrakis; Joel D Schwartz; Richard L Verrier Journal: Environ Health Perspect Date: 2005-06 Impact factor: 9.031
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