Grantee Research Project Results
Final Report: Cardiovascular Responses in the Normative Aging Study: Exploring the Pathways of Particle Toxicity
EPA Grant Number: R832416C001Subproject: this is subproject number 001 , established and managed by the Center Director under grant R832416
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Health Effects Institute (2015 - 2020)
Center Director: Greenbaum, Daniel S.
Title: Cardiovascular Responses in the Normative Aging Study: Exploring the Pathways of Particle Toxicity
Investigators: Schwartz, Joel , Suh, Helen H. , Sparrow, David , Vokonas, Pantel
Institution: Harvard University
EPA Project Officer: Chung, Serena
Project Period: October 1, 2005 through September 30, 2010 (Extended to September 30, 2011)
RFA: Particulate Matter Research Centers (2004) RFA Text | Recipients Lists
Research Category: Human Health , Air
Objective:
This project was a follow-up to the research included in Harvard School of Public Health's (HSPH) original EPA-funded Particle Center, where we examined air pollution mediated responses of individuals participating in the Normative Aging Study (NAS), a large prospective cohort living in Eastern Massachusetts. As part of this effort, we collected electrocardiograms (ECGs) and blood samples from each study participant and analyzed these samples for heart rate variability (HRV) and C-reactive protein (CRP), respectively. In analyses of these data, we found ambient PM2.5 and ambient black carbon (BC) concentrations to be associated with decrements in HRV, with these decrements greatest for hypertensive individuals. Ambient BC concentrations were further found to be associated with increased CRP and fibrinogen levels. These results suggested that the PM-mediated autonomic changes may be brought about through pathways involving the autonomic nervous system and systemic inflammation. Definitive identification of PM-mediated biological mechanisms was limited, however, by the lack of other intermediate cardiac and inflammation endpoints, the use of central site monitoring to characterize exposures for the entire cohort, and by the traditional epidemiologic approaches used to examine exposure-effect associations.
For Project 1 of the second HSPH Center, we did further research using the NAS cohort, with continued ECG, CRP and fibrinogen measurements, and importantly, with additional exposure and health measurements for each NAS participant to enhance our ability to identify important biological pathways. These additional measurements included ECG, blood inflammatory markers, medication, genotypic, food frequency, and particle exposure measurements for each of the current NAS participants. ECG and blood samples were analyzed for a variety of measures (HRV, ST segments, QT intervals, CRP, sICAM-1, sVCAM-1, and homocysteine); these measures were used as intermediate markers of the inflammatory, endothelial, and autonomic pathways. In addition, these measures are related to individual-specific indoor PM2.5, SO42-, and BC exposures that were measured for 1 week inside the subject’s home prior to the clinic visit and to ambient air pollution (PM2.5, PM10, PM2.5-10, SO42‑, NO3-, BC, EC, OC, and PC) concentrations that were measured at our stationary ambient monitoring (SAM) site. The study used these data to test three primary hypotheses:
- acute inflammation and/or endothelial dysfunction, as measured by increases in CRP, soluble intercellular adhesion molecule 1 (sICAM-1), and soluble vascular cell adhesion molecule 1 (sVCAM-1);
- autonomic dysfunction, as measured by reduced HRV and;
- general cardiovascular responses, as measured by increases in blood pressure and ECG changes including ST-segment level and QT-interval.
- oxidative stress, endothelial dysfunction, and/or acute inflammation, specifically Glutathione-s-transferase (GSTM1) null or the long repeat Hemeoxygenase-1 (HO-1) genotypes; statin, beta blocker, or calcium channel blocker use; dietary intake of Vitamin C or omega-3 (Ω-3) fatty acids;
- autonomic dysfunction, specifically beta blocker use, calcium channel blocker use or dietary intake of Ω-3 fatty acids;
- general cardiovascular disease, specifically hypertension, and;
- reactive airways disease, specifically methacholine reactivity.
Summary/Accomplishments (Outputs/Outcomes):
Conclusions:
References:
Journal Articles on this Report : 46 Displayed | Download in RIS Format
Other subproject views: | All 68 publications | 67 publications in selected types | All 67 journal articles |
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Other center views: | All 206 publications | 199 publications in selected types | All 199 journal articles |
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Alexeeff SE, Litonjua AA, Suh H, Sparrow D, Vokonas PS, Schwartz J. Ozone exposure and lung function: effect modified by obesity and airways hyperresponsiveness in the VA Normative Aging Study. Chest 2007;132(6):1890-1897. |
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Alexeeff SE, Litonjua AA, Sparrow D, Vokonas PS, Schwartz J. Statin use reduces decline in lung function: VA Normative Aging Study. American Journal of Respiratory and Critical Care Medicine 2007;176(8):742-747. |
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Alexeeff SE, Litonjua AA, Wright RO, Baccarelli A, Suh H, Sparrow D, Vokonas PS, Schwartz J. Ozone exposure, antioxidant genes, and lung function in an elderly cohort:VA Normative Aging Study. Occupational and Environmental Medicine 2008;65(11):736-742. |
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Alexeeff SE, Coull BA, Gyparis A, Suh H, Sparrow D, Vokonas PS, Schwartz J. Medium-term exposure to traffic-related air pollution and markers of inflammation and endothelial function. Environmental Health Perspectives 2011;119(4):481-486. |
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Baccarelli A, Cassano PA, Litonjua A, Park SK, Suh H, Sparrow D, Vokonas P, Schwartz J. Cardiac autonomic dysfunction: effects from particulate air pollution and protection by dietary methyl nutrients and metabolic polymorphisms. Circulation 2008;117(14):1802-1809. |
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Baccarelli A, Martinelli I, Zanobetti A, Grillo P, Hou L-F, Bertazzi PA, Mannucci PM, Schwartz J. Exposure to particulate air pollution and risk of deep vein thrombosis. Archives of Internal Medicine 2008;168(9):920-927. |
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Baccarelli A, Wright RO, Bollati V, Tarantini L, Litonjua AA, Suh HH, Zanobetti A, Sparrow D, Vokonas PS, Schwartz J. Rapid DNA methylation changes after exposure to traffic particles. American Journal of Respiratory and Critical Care Medicine 2009;179(7):572-578. |
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Baccarelli A, Tarantini L, Wright RO, Bollati V, Litonjua AA, Zanobetti A, Sparrow D, Vokonas PS, Schwartz J. Repetitive element DNA methylation and circulating endothelial and inflammation markers in the VA Normative Aging Study. Epigenetics 2010;5(3):222-228. |
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Baccarelli A, Wright R, Bollati V, Litonjua A, Zanobetti A, Tarantini L, Sparrow D, Vokonas P, Schwartz J. Ischemic heart disease and stroke in relation to blood DNA methylation. Epidemiology 2010;21(6):819-828. |
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Baja ES, Schwartz JD, Wellenius GA, Coull BA, Zanobetti A, Vokonas PS, Suh HH. Traffic-related air pollution and QT interval: modification by diabetes, obesity, and oxidative stress gene polymorphisms in the Normative Aging Study. Environmental Health Perspectives 2010;118(6):840-846. |
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Bind MA, Baccarelli A, Zanobetti A, Tarantini L, Suh H, Vokonas P, Schwartz J. Air pollution and markers of coagulation, inflammation, and endothelial function:associations of epigene-environment Interactions in an elderly cohort. Epidemiology 2012;23(2):332-340. |
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Bollati V, Schwartz J, Wright R, Litonjua A, Tarantini L, Suh H, Sparrow D, Vokonas P, Baccarelli A. Decline in genomic DNA methylation through aging in a cohort of elderly subjects. Mechanisms of Ageing and Development 2009;130(4):234-239. |
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Chahine T, Baccarelli A, Litonjua A, Wright RO, Suh H, Gold DR, Sparrow D, Vokonas P, Schwartz J. Particulate air pollution, oxidative stress genes, and heart rate variability in an elderly cohort. Environmental Health Perspectives 2007;115(11):1617-1622. |
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Chen J-C, Schwartz J. Metabolic syndrome and inflammatory responses to long-term particulate air pollutants. Environmental Health Perspectives 2008;116(5):612-617. |
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Chen J-C, Schwartz J. Neurobehavioral effects of ambient air pollution on cognitive performance in US adults. NeuroToxicology 2009;30(2):231-239. |
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Dioni L, Hoxha M, Nordio F, Bonzini M, Tarantini L, Albetti B, Savarese A, Schwartz J, Bertazzi PA, Apostoli P, Hou L, Baccarelli A. Effects of short-term exposure to inhalable particulate matter on telomere length, telomerase expression, and telomerase methylation in steel workers. Environmental Health Perspectives 2011;119(5):622-627. |
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Halonen JI, Zanobetti A, Sparrow D, Vokonas PS, Schwartz J. Associations between outdoor temperature and markers of inflammation:a cohort study. Environmental Health 2010;9:42 (9 pp.). |
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Halonen JI, Zanobetti A, Sparrow D, Vokonas PS, Schwartz J. Relationship between outdoor temperature and blood pressure. Occupational and Environmental Medicine 2011;68(4):296-301. |
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Hoffmann B, Luttmann-Gibson H, Cohen A, Zanobetti A, de Souza C, Foley C, Suh HH, Coull BA, Schwartz J, Mittleman M, Stone P, Horton E, Gold DR. Opposing effects of particle pollution, ozone, and ambient temperature on arterial blood pressure. Environmental Health Perspectives 2012;120(2):241-246. |
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Levy JI, Diez D, Dou Y, Barr CD, Dominici F. A meta-analysis and multisite time-series analysis of the differential toxicity of major fine particulate matter constituents. American Journal of Epidemiology 2012;175(11):1091-1099. |
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Madrigano J, Baccarelli A, Wright RO, Suh H, Sparrow D, Vokonas PS, Schwartz J. Air pollution, obesity, genes and cellular adhesion molecules. Occupational and Environmental Medicine 2010;67(5):312-317. |
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Madrigano J, Baccarelli A, Mittleman MA, Wright RO, Sparrow D, Vokonas PS, Tarantini L, Schwartz J. Prolonged exposure to particulate pollution, genes associated with glutathione pathways, and DNA methylation in a cohort of older men. Environmental Health Perspectives 2011;119(7):977-982. |
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McCracken J, Baccarelli A, Hoxha M, Dioni L, Melly S, Coull B, Suh H, Vokonas P, Schwartz J. Annual ambient black carbon associated with shorter telomeres in elderly men: Veterans Affairs Normative Aging Study. Environmental Health Perspectives 2010;118(11):1564-1570. |
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McCracken J, Smith KR, Stone P, Diaz A, Arana B, Schwartz J. Intervention to lower household wood smoke exposure in Guatemala reduces ST-segment depression on electrocardiograms. Environmental Health Perspectives 2011;119(11):1562-1568. |
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Medina-Ramon M, Goldberg R, Melly S, Mittleman MA, Schwartz J. Residential exposure to traffic-related air pollution and survival after heart failure. Environmental Health Perspectives 2008;116(4):481-485. |
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Mordukhovich I, Wilker E, Suh H, Wright R, Sparrow D, Vokonas PS, Schwartz J. Black carbon exposure, oxidative stress genes, and blood pressure in a repeated-measures study. Environmental Health Perspectives 2009;117(11):1767-1772. |
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Park SK, O’Neill MS, Vokonas PS, Sparrow D, Spiro III A, Tucker KL, Suh H, Hu H, Schwartz J. Traffic-related particles are associated with elevated homocysteine: the VA Normative Aging Study. American Journal of Respiratory and Critical Care Medicine 2008;178(3):283-289. |
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Park SK, O’Neill MS, Vokonas PS, Sparrow D, Wright RO, Coull B, Nie H, Hu H, Schwartz J. Air pollution and heart rate variability: effect modification by chronic lead exposure. Epidemiology 2008;19(1):111-120. |
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Park SK, Tucker KL, O'Neill MS, Sparrow D, Vokonas PS, Hu H, Schwartz J. Fruit, vegetable, and fish consumption and heart rate variability: the Veterans Administration Normative Aging Study. American Journal of Clinical Nutrition 2009;89(3):778-786. |
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Peters JL, Kubzansky LD, Ikeda A, Spiro III A, Wright RO, Weisskopf MG, Kim D, Sparrow D, Nie LH, Hu H, Schwartz J. Childhood and adult socioeconomic position, cumulative lead levels, and pessimism in later life: the VA Normative Aging Study. American Journal of Epidemiology 2011;174(12):1345-1353. |
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Peters JL, Kubzansky LD, Ikeda A, Fang SC, Sparrow D, Weisskopf MG, Wright RO, Vokonas P, Hu H, Schwartz J. Lead concentrations in relation to multiple biomarkers of cardiovascular disease: the Normative Aging Study. Environmental Health Perspectives 2012;120(3):361-366. |
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Ren C, Vokonas PS, Suh H, Fang S, Christiani DC, Schwartz J. Effect modification of air pollution on urinary 8-hydroxy-2'-deoxyguanosine by genotypes: an application of the multiple testing procedure to identify significant SNP interactions. Environmental Health 2010;9:78 (9 pp.). |
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Ren C, Melly S, Schwartz J. Modifiers of short-term effects of ozone on mortality in eastern Massachusetts—a case-crossover analysis at individual level. Environmental Health 2010;9:3 (10 pp.). |
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Ren C, Baccarelli A, Wilker E, Suh H, Sparrow D, Vokonas P, Wright R, Schwartz J. Lipid and endothelium-related genes, ambient particulate matter, and heart rate variability—the VA Normative Aging Study. Journal of Epidemiology and Community Health 2010;64(1):49-56. |
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Ren C, Park SK, Vokonas PS, Sparrow D, Wilker E, Baccarelli A, Suh HH, Tucker KL, Wright RO, Schwartz J. Air pollution and homocysteine: more evidence that oxidative stress-related genes modify effects of particulate air pollution. Epidemiology 2010;21(2):198-206. |
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Ren C, O'Neill MS, Park SK, Sparrow D, Vokonas P, Schwartz J. Ambient temperature, air pollution, and heart rate variability in an aging population. American Journal of Epidemiology 2011;173(9):1013-1021. |
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Schwartz J, Sarnat JA, Coull BA, Wilson WE. Effects of exposure measurement error on particle matter epidemiology:a simulation using data from a panel study in Baltimore, MD. Journal of Exposure Science and Environmental Epidemiology 2007;17(Suppl 2):S2-S10. |
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Wellenius GA, Yeh GY, Coull BA, Suh HH, Phillips RS, Mittleman MA. Effects of ambient air pollution on functional status in patients with chronic congestive heart failure: a repeated-measures study. Environmental Health 2007;6:26. |
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Wilker EH, Alexeeff SE, Poon A, Litonjua AA, Sparrow D, Vokonas PS, Mittleman MA, Schwartz J. Candidate genes for respiratory disease associated with markers of inflammation and endothelial dysfunction in elderly men. Atherosclerosis 2009;206(2):480-485. |
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Wilker EH, Baccarelli A, Suh H, Vokonas P, Wright RO, Schwartz J. Black carbon exposures, blood pressure, and interactions with single nucleotide polymorphisms in microRNA processing genes. Environmental Health Perspectives 2010;118(7):943-948. |
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Wilker EH, Alexeeff SE, Suh H, Vokonas PS, Baccarelli A, Schwartz J. Ambient pollutants, polymorphisms associated with microRNA processing and adhesion molecules:the Normative Aging Study. Environmental Health 2011;10:45. |
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Wilker E, Mittleman MA, Litonjua AA, Poon A, Baccarelli A, Suh H, Wright RO, Sparrow D, Vokonas P, Schwartz J. Postural changes in blood pressure associated with interactions between candidate genes for chronic respiratory diseases and exposure to particulate matter. Environmental Health Perspectives 2009;117(6):935-940. |
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Zanobetti A, Baccarelli A, Schwartz J. Gene-air pollution interaction and cardiovascular disease: a review. Progress in Cardiovascular Diseases 2011;53(5):344-352. |
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Zanobetti A, Schwartz J. Ozone and survival in four cohorts with potentially predisposing diseases. American Journal of Respiratory and Critical Care Medicine 2011;184(7):836-841. |
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Zhu ZZ, Sparrow D, Hou L, Tarantini L, Bollati V, Litonjua AA, Zanobetti A, Vokonas P, Wright RO, Baccarelli A, Schwartz J. Repetitive element hypomethylation in blood leukocyte DNA and cancer incidence, prevalence, and mortality in elderly individuals: the Normative Aging Study. Cancer Causes & Control 2011;22(3):437-447. |
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Zhu ZZ, Hou L, Bollati V, Tarantini L, Marinelli B, Cantone L, Yang AS, Vokonas P, Lissowska J, Fustinoni S, Pesatori AC, Bonzini M, Apostoli P, Costa G, Bertazzi PA, Chow WH, Schwartz J, Baccarelli A. Predictors of global methylation levels in blood DNA of healthy subjects: a combined analysis. International Journal of Epidemiology 2012;41(1):126-139. |
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Supplemental Keywords:
RFA, Health, Scientific Discipline, Air, particulate matter, Environmental Chemistry, Health Risk Assessment, Epidemiology, Risk Assessments, ambient air quality, atmospheric particulate matter, biological pathways, chemical characteristics, human health effects, toxicology, airborne particulate matter, cardiovascular vulnerability, automobile exhaust, biological mechanisms, traffic related particulate matter, chemical composition, biological mechanism , human exposure, ambient particle health effects, autonomic dysfunction, oxidative stressProgress and Final Reports:
Original AbstractMain Center Abstract and Reports:
R832416 Health Effects Institute (2015 - 2020) Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R832416C001 Cardiovascular Responses in the Normative Aging Study: Exploring the Pathways of Particle Toxicity
R832416C002 Cardiovascular Toxicity of Concentrated Ambient Fine, Ultrafine and Coarse Particles in Controlled Human Exposures
R832416C003 Assessing Toxicity of Local and Transported Particles Using Animal Models Exposed to CAPs
R832416C004 Cardiovascular Effects of Mobile Source Exposures: Effects of Particles and Gaseous Co-pollutants
R832416C005 Toxicological Evaluation of Realistic Emission Source Aerosol (TERESA): Investigation of Vehicular Emissions
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.
Project Research Results
- 2010 Progress Report
- 2009 Progress Report
- 2008 Progress Report
- 2007 Progress Report
- 2006 Progress Report
- Original Abstract
67 journal articles for this subproject
Main Center: R832416
206 publications for this center
199 journal articles for this center