Final Report: Cardiovascular Responses in the Normative Aging Study: Exploring the Pathways of Particle Toxicity

EPA Grant Number: R832416C001
Subproject: 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: Harvard Particle Center
Center Director: Koutrakis, Petros
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: Health Effects , 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:

Hypothesis 1:  Cardiovascular effects of particles (PM) differ by source and by different source-related components. Specifically, short-term exposures to sulfate and traffic particles will be associated with increases in:
  • 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.
Hypothesis 2:  Effects of PM on these outcomes are modified by subject characteristics (genetic, dietary, or pharmacological) that influence susceptibility to:
  • 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.
Hypothesis 3: Long-term exposure to PM from traffic is associated with increased risk of inflammation (e.g., CRP, sICAM-1, sVCAM-1, and homocysteine); autonomic dysfunction (e.g., reduced HRV), and impaired cardiovascular outcomes (e.g., elevated blood pressure). This association is modified by the same factors that modify acute responses.

Summary/Accomplishments (Outputs/Outcomes):

The NAS cohort has informed us about toxicity of PM2.5, BC, O3 and SO42- on autonomic dysfunction, inflammation, and endothelial dysfunction. We also have gained new insights on individuals at higher risk, such as those with obesity or diabetes. Moreover, we have studied genetic susceptibility factors that inform us about both at-risk groups and possible mechanisms of action of PM. We began exploring multiple pollutants and interactions, and new outcomes including cognition and biomarkers of oxidative stress. We highlight results from our NAS studies below.
 
Multiple pollutants and interactions: We have extended beyond our single-pollutant models to investigate multiple-pollutant models and pollutant interactions. We have demonstrated that higher cumulative lead exposures (predominantly from past gasoline lead) modified associations between air pollution and HRV among our NAS subjects (Park, et al., 2008a). We found graded, significant reductions in both high- and low-frequency (HF and LF) powers of HRV in relation to O3 and SO42- across quartiles of tibia lead (Park, et al., 2006). We also found that polymorphisms of the hemochromatosis (HFE) gene protected against the effects of PM2.5 on HRV (Park, et al., 2006). Two polymorphisms in the HFE gene (C282Y and H63D) are associated with increased uptake of Fe and other transition metals into cells as compared to the wild type genotype, hence our results suggest a role of transition metals in this PM2.5 effect. Concerning air pollution sources and mixtures, we have examined the differences in impact of PM2.5 on HRV by air mass origin using “back-trajectories” (Park, et al., 2007). We found that the effects of BC on all HRV measures were strongest on days with southwest trajectories, while the strongest associations of HRV with O3 occurred on days when air parcels came from the west. PM2.5, BC, and SO42- were associated with increased LF/HF ratio on days related to local, slow moving air masses.
 
Black Carbon Spatio-temporal model: We developed a GIS-based spatial smoothing model to predict 24-hr BC levels. We used this model to predict address-specific exposures for NAS subjects and for subjects in other Boston-area cohorts. We identified an inverse association between address-specific annual BC and telomere length in NAS subjects, using predicted BC from this model (McCracken, et al., 2009).
 
Inflammation, Endothelial Function, and Oxidative Stress: We observed positive associations between traffic-related PM (particle number and black carbon) and inflammatory markers (CRP, WBC count, sediment rate, and fibrinogen) among subjects in the NAS cohort (Zeka, et al., 2006). A follow-up study looking at repeated measures of CRP and fibrinogen now is under review (Bind, et al., in review). We also found that exposures to traffic-related PM (black and organic carbon) were associated with elevated plasma total homocysteine (Park, et al., 2008b). A follow-up analysis showed effect modification by genes related to oxidative stress (Ren, et al., 2010a). PM2.5 and black carbon were associated with increased vascular cell adhesion in subjects and this association was modified by obesity, and by genes (Wilker, et al., 2009). Finally, we report associations between 8-OHdG and both PM2.5 and SO42-, but not BC in a cross-sectional study (Ren, et al., 2010b).
 
Autonomic Dysfunction: We reported an association between short-term PM2.5 exposure and decreased HRV (Park, et al., 2005). We found that subjects with wild type endothelial related genes (APOE, LPL and VEGF) showed stronger effects of PM2.5 on HRV compared to those with hetero- or homozygous genotypes (Ren, et al., 2010c). We found a negative association between PM2.5 and HRV in subjects with lower dietary intakes of methyl nutrients (folate, vitamins B(6) and B(12), methionine), but not in subjects with higher intakes. This association also was modified by methyl-related gene polymorphisms in MTHFR and cSHMT genes and genes related to oxidative stress (Chahine, et al., 2007).
 
Telomere Length: We recently have reported that exposure to traffic was associated with shortened telomere length in blood leukocytes in a study comparing traffic officers to controls (Hoxha, et al., 2009). Preliminary results among nonsmokers in the NAS show an association between shorter telomere length and address-specific annual BC (under review).
 
Susceptibility: In addition to looking at genetic and dietary susceptibility factors, we have investigated obesity and diabetes as susceptibility factors for increased risk to air pollution responsiveness. We found obesity to be a significant susceptibility factor for O3 acute effects on lung function, with twice the estimated decrease in FEV1 due to O3 in obese subjects compared to non-obese subjects (Alexeev, et al., 2007). In addition, we found a greater effect of traffic-related PM on inflammatory markers in obese individuals (Zeka, et al., 2006).

Conclusions:

Follow-up Research
 
The findings of the NAS study indicate that additional research would be fruitful for continuing investigations of impacts of air pollution on health, which currently are being conducted under our EPA-funded Clear Air Research Center (CLARC).
 
Continuing measurements of 8-OHdG in NAS subjects would improve our estimates of oxidative stress effects. The results from processing our second set of measurements of augmentation index, telomere length, and 8-OHdG would be quite useful, along with collection of more data. Repeated measurements on each subject would have the power to examine effect modification by multiple sources of susceptibility and vulnerability. It also would be useful to expand our suite of inflammatory markers to include IL6.
 
Analysis of the sub-clinical effects of temperature would allow us to better understand the mechanisms underlying the effects of temperature on mortality. It also would be worthwhile to use our spatio-temporal model of BC to identify associations between long-term exposure to BC and decreased telomere length as well as increased blood pressure. Analysis of many of our other outcomes in relation to our modeled BC exposures also would be useful.
 
Epigenetics would be helpful to study the effects of genes both directly, and as modifiers of responses to pollution, where certain subpopulations have genetic profiles that put them at increased risk to the health effects of air pollution. It also would be worthwhile to continue to study gene methylation, an important indicator of gene activation. In addition, it would be useful to perform novel analyses of MicroRNAs, examining whether they mediate the effects of environmental pollutants on human health, because certain miRNA profiles have been associated with cardiovascular disorders as well as vascular inflammation.

References:

Alexeeff SE, Litonjua AA, Suh H, Sparrow D, Vokonas P, Schwartz J: Ozone exposure and lung function: effect modified by obesity, airways hyperresponsiveness in the VA Normative Aging Study. Chest 2007;132:1890-1897.
 
Bind M-L, Zanobetti A, Suh H, Vokonas P, Schwartz J. Air pollution and inflammatory markers in an elderly cohort: VA Normative Aging Study. (under review 2012).
 
Chahine T, Baccarelli A, Litonjua A, et al. Particulate air pollution, oxidative stress genes, and heart rate variability in an elderly cohort. Environ Health Perspect 2007;115:1617-1622.
 
Hoxha M, Dioni L, Bonzini M, et al. Association between leukocyte telomere shortening and exposure to traffic pollution: a cross-sectional study on traffic officers and indoor office workers. Environ Health 2009;8:41.
 
McCracken J, Baccarelli A, Barbullushi M, Dioni L, Suh H, Wright R, Vokonas P, Schwartz J. Annual ambient black carbon associated with shorter telomeres in the Greated Boston Area. Epidemiology 2009;20(6):S70.
 
Park SK, O'Neill MS, Vokonas PS, Sparrow D, Schwartz J. Effects of air pollution on heart rate variability: the VA normative aging study. Environ Health Perspect 2005;113:304-309.
 
Park SK, O'Neill MS, Wright RO, et al. HFE genotype, particulate air pollution, and heart rate variability: a gene-environment interaction. Circulation 2006;114:2798-2805.
 
Park SK, O'Neill MS, Stunder BJ, et al. Source location of air pollution and cardiac autonomic function: trajectory cluster analysis for exposure assessment. J Expo Sci Environ Epidemiol 2007;17:488-497.
 
Park SK, O'Neill MS, Vokonas PS, et al. Air pollution and heart rate variability: effect modification by chronic lead exposure. Epidemiology 2008a;19:111-120.
 
Park SK, O'Neill MS, Vokonas PS, et al. Traffic-related particles are associated with elevated homocysteine: the VA normative aging study. Am J Respir Crit Care Med 2008b;178:283-289.
 
Ren, CZ , 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 2010a;21(2):198-206.
 
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 2010b;9:78 (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3016327/pdf/1476-069X-9-78.pdf).
 
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 2010c;49-56.
 
Wilker E, Mittleman MA, Litonjua AA, et al. Postural changes in blood pressure associated with interactions between candidate genes for chronic respiratory diseases and exposure to particulate matter. Environ Health Perspect 2009;117:935-940.
 
Zeka A, Sullivan JR, Vokonas PS, Sparrow D, Schwartz J. Inflammatory markers and particulate air pollution: characterizing the pathway to disease. Int J Epidemiol 2006;35:1347-1354.


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
Other center views: All 200 publications 194 publications in selected types All 194 journal articles
Type Citation Sub Project Document Sources
Journal Article 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. R832416 (2006)
R832416 (2009)
R832416 (Final)
R832416C001 (2008)
R832416C001 (2009)
R832416C001 (Final)
R827353 (Final)
  • Abstract from PubMed
  • Full-text: ScienceDirect-Full Text-HTML
    Exit
  • Abstract: ScienceDirectt-Abstract
    Exit
  • Other: ScienceDirect-Full Text-PDF
    Exit
  • Journal Article 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. R832416 (2006)
    R832416 (Final)
    R832416C001 (2008)
    R832416C001 (Final)
    R827353 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: AJRRCM-Full Text HTML
    Exit
  • Abstract: AJRRCM-Abstract
    Exit
  • Other: AJRRCM-Full Text PDF
    Exit
  • Journal Article 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. R832416 (Final)
    R832416C001 (2008)
    R832416C001 (Final)
    R827353 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: ResearchGate-Abstract and Full Text PDF
    Exit
  • Abstract: OEM-Abstract
    Exit
  • Journal Article 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. R832416 (Final)
    R832416C001 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: EHP-Full Text PDF
  • Abstract: EHP-Abstract & Full Text HTML
  • Journal Article 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. R832416 (2006)
    R832416 (Final)
    R832416C001 (2008)
    R832416C001 (Final)
    R827353 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: Circulation-Full Text HTML
    Exit
  • Abstract: Circulation-Abstract
    Exit
  • Other: Circulation-Full Text PDF
    Exit
  • Journal Article 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. R832416 (2006)
    R832416 (Final)
    R832416C001 (2008)
    R832416C001 (Final)
    R827353 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: ResearchGate-Full Text PDF
    Exit
  • Abstract: Archives of Internal Medicine-Abstract & Full Text HTML
    Exit
  • Journal Article 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. R832416 (Final)
    R832416C001 (2010)
    R832416C001 (Final)
    R827353 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: AJRCCM-Full Text HTML
    Exit
  • Other: AJRCCM-Full Text PDF
    Exit
  • Journal Article 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. R832416 (Final)
    R832416C001 (2010)
    R832416C001 (Final)
    R827353 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: Taylor & Francis-Full Text PDF
    Exit
  • Abstract: Taylor & Francis-Abstract
    Exit
  • Journal Article 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. R832416 (Final)
    R832416C001 (Final)
    R827353 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: ResearchGate-Abstract & Full Text PDF
    Exit
  • Abstract: Epidemiology-Abstract
    Exit
  • Journal Article 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. R832416 (Final)
    R832416C001 (2010)
    R832416C001 (Final)
    R827353 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: EHP-Full Text PDF
  • Abstract: EHP-Abstract and Full Text HTML
  • Journal Article 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. R832416 (Final)
    R832416C001 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: ResearchGate-Full Text HTML
    Exit
  • Abstract: Ovid-Abstract
    Exit
  • Journal Article 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. R832416 (Final)
    R832416C001 (Final)
    R827353 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: ScienceDirect-Full Text HTML
    Exit
  • Abstract: ScienceDirect-Abstract
    Exit
  • Other: ScienceDirect-Full Text PDF
    Exit
  • Journal Article 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. R832416 (2006)
    R832416 (2008)
    R832416 (2009)
    R832416 (Final)
    R832416C001 (2008)
    R832416C001 (2009)
    R832416C001 (Final)
    R827353 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: ResearchGate-Full Text PDF
    Exit
  • Other: Harvard University-Full Text PDF
    Exit
  • Journal Article Chen J-C, Schwartz J. Metabolic syndrome and inflammatory responses to long-term particulate air pollutants. Environmental Health Perspectives 2008;116(5):612-617. R832416 (2006)
    R832416 (Final)
    R832416C001 (Final)
    R827353 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: Harvard-Full Text PDF
    Exit
  • Journal Article Chen J-C, Schwartz J. Neurobehavioral effects of ambient air pollution on cognitive performance in US adults. NeuroToxicology 2009;30(2):231-239. R832416 (Final)
    R832416C001 (2010)
    R832416C001 (Final)
    R827353 (Final)
  • Abstract from PubMed
  • Full-text: ScienceDirect-Full Text HTML
    Exit
  • Abstract: ScienceDirect-Abstract
    Exit
  • Other: ScienceDirect-Full Text PDF
    Exit
  • Journal Article 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. R832416 (Final)
    R832416C001 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: EHP-Full Text PDF
  • Abstract: EHP-Abstract & Full Text HTML
  • Journal Article 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.). R832416 (Final)
    R832416C001 (2010)
    R832416C001 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: Environmental Health-Full Text HTML
    Exit
  • Abstract: Environmental Health-Abstract
    Exit
  • Other: Environmental Health-Full Text PDF
    Exit
  • Journal Article 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. R832416 (Final)
    R832416C001 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Abstract: OEM-Abstract
    Exit
  • Journal Article 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. R832416 (Final)
    R832416C001 (Final)
    R834798 (2012)
    R834798 (2013)
    R834798 (2014)
    R834798 (2015)
    R834798 (Final)
    R834798C001 (2014)
    R834798C002 (Final)
    R834798C004 (2012)
    R834798C004 (2014)
    R834798C004 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: EHP-Full Text PDF
  • Abstract: EHP-Abstract & Full Text HTML
  • Other: ResearchGate-Abstract & Full Text PDF
    Exit
  • Journal Article 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. R832416C001 (Final)
    R832417 (Final)
    R834798 (2012)
    R834798 (2013)
    R834798 (2014)
    R834798 (2015)
    R834798 (Final)
    R834798C001 (2014)
    R834798C005 (2012)
    R834798C005 (Final)
    R834894 (2012)
    R834894 (2013)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: AJE-Full Text HTML
    Exit
  • Abstract: AJE-Abstract
    Exit
  • Other: AJE-Full Text PDF
    Exit
  • Journal Article 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. R832416 (Final)
    R832416C001 (Final)
    R827353 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: ResearchGate-Abstract & Full Text PDF
    Exit
  • Abstract: BMJ-Abstract
    Exit
  • Journal Article 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. R832416 (Final)
    R832416C001 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: EHP-Full Text PDF
  • Abstract: EHP-Abstract & Full Text HTML
  • Journal Article 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. R832416 (Final)
    R832416C001 (Final)
    R827353 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: EHP-Full Text HTML
    Exit
  • Other: EHP-Full Text PDF
  • Journal Article 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. R832416 (Final)
    R832416C001 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: EHP-Full Text PDF
  • Abstract: EHP-Abstract & Full Text HTML
  • Journal Article 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. R832416 (2006)
    R832416 (2008)
    R832416 (Final)
    R832416C001 (2008)
    R832416C001 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: Harvard University-Full Text PDF
    Exit
  • Journal Article 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. R832416 (Final)
    R832416C001 (2010)
    R832416C001 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: EHP-Full Text PDF
  • Abstract: EHP-Abstract & Full Text HTML
  • Journal Article 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. R832416 (2006)
    R832416 (2009)
    R832416 (Final)
    R832416C001 (2008)
    R832416C001 (2009)
    R832416C001 (Final)
    R827353 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: AJRCCM-Full Text HTML
    Exit
  • Abstract: AJRCCM-Abstract
    Exit
  • Other: AJRCCM-Full Text PDF
    Exit
  • Journal Article 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. R832416 (2006)
    R832416 (2009)
    R832416 (Final)
    R832416C001 (2008)
    R832416C001 (2009)
    R832416C001 (Final)
    R827353 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: Epidemiology-Full Text HTML
    Exit
  • Abstract: Epidemiology-Abstract
    Exit
  • Other: Epidemiology-Full Text PDF
    Exit
  • Journal Article 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. R832416 (Final)
    R832416C001 (2010)
    R832416C001 (Final)
    R827353 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: AJCN-Full Text HTML
    Exit
  • Other: AJCN-Full Text PDF
    Exit
  • Journal Article 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. R832416 (Final)
    R832416C001 (Final)
    R834798 (2010)
    R834798 (2011)
    R834798 (2014)
    R834798 (2015)
    R834798 (Final)
    R834798C001 (2014)
    R834798C001 (Final)
    R834798C002 (2010)
    R834798C002 (2011)
    R834798C002 (2014)
    R834798C002 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: AJE-Full Text HTML
    Exit
  • Abstract: AJE-Abstract
    Exit
  • Other: AJE-Full Text PDF
    Exit
  • Journal Article 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. R832416 (Final)
    R832416C001 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: EHP-Full Text HTML
  • Abstract: EHP-Abstract
  • Other: EHP-Full Text PDF
  • Journal Article 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.). R832416 (Final)
    R832416C001 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: Environmental Health-Full Text HTML
    Exit
  • Abstract: Environmental Health-Abstract
    Exit
  • Other: Environmental Health-Full Text PDF
    Exit
  • Journal Article 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.). R832416 (Final)
    R832416C001 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: Environmental Health-Full Text HTML
    Exit
  • Abstract: Environmental Health-Abstract
    Exit
  • Other: Environmental Health-Full Text PDF
    Exit
  • Journal Article 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. R832416 (2009)
    R832416 (Final)
    R832416C001 (2009)
    R832416C001 (2010)
    R832416C001 (Final)
    R827353 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Abstract: JECH-Abstract
    Exit
  • Journal Article 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. R832416 (2009)
    R832416 (Final)
    R832416C001 (2009)
    R832416C001 (2010)
    R832416C001 (Final)
    R827353 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Abstract: Epidemiology-Abstract
    Exit
  • Journal Article 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. R832416 (Final)
    R832416C001 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: AJE-Full Text HTML
    Exit
  • Abstract: AJE-Abstract
    Exit
  • Other: AJE-Full Text PDF
    Exit
  • Journal Article 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. R832416 (2008)
    R832416 (Final)
    R832416C001 (2008)
    R832416C001 (Final)
  • Abstract from PubMed
  • Full-text: Nature-Full Text PDF
    Exit
  • Abstract: Nature-Abstract & Full Text HTML
    Exit
  • Journal Article 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. R832416 (2006)
    R832416 (Final)
    R832416C001 (Final)
    R827353 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: Environmental Health-Full Text HTML
    Exit
  • Abstract: Environmental Health-Abstract
    Exit
  • Other: Environmental Health-Full Text PDF
    Exit
  • Journal Article 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. R832416 (2009)
    R832416 (Final)
    R832416C001 (2009)
    R832416C001 (2010)
    R832416C001 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: ResearchGate-Abstract
    Exit
  • Abstract: Atherosclerosis-Abstract
    Exit
  • Journal Article 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. R832416 (Final)
    R832416C001 (2010)
    R832416C001 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: EHP-Full Text PDF
  • Abstract: EHP-Abstract & Full Text HTML
  • Journal Article 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. R832416 (Final)
    R832416C001 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: Environmental Health-Full Text HTML
    Exit
  • Abstract: Environmental Health-Abstract
    Exit
  • Other: Environmental Health-Full Text PDF
    Exit
  • Journal Article 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. R832416 (Final)
    R832416C001 (2010)
    R832416C001 (Final)
    R827353 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: EHP-Full Text PDF
  • Abstract: EHP-Abstract and Full Text HTML
  • Journal Article Zanobetti A, Baccarelli A, Schwartz J. Gene-air pollution interaction and cardiovascular disease: a review. Progress in Cardiovascular Diseases 2011;53(5):344-352. R832416 (Final)
    R832416C001 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: ResearchGate-Abstract & Full Text PDF
    Exit
  • Abstract: ScienceDIrect-Abstract
    Exit
  • Journal Article 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. R832416 (Final)
    R832416C001 (Final)
    R834798 (2010)
    R834798 (2011)
    R834798 (2013)
    R834798 (2014)
    R834798 (2015)
    R834798 (Final)
    R834798C001 (2014)
    R834798C001 (Final)
    R834798C002 (2010)
    R834798C002 (2011)
    R834798C002 (2014)
    R834798C002 (Final)
    R834798C005 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: AJRCCM-Full Text HTML
    Exit
  • Abstract: AJRCCM-Abstract
    Exit
  • Other: AJRCCM-Full Text PDF
    Exit
  • Journal Article 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. R832416 (Final)
    R832416C001 (Final)
    R827353 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Abstract: Springer-Abstract
    Exit
  • Journal Article 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. R832416 (Final)
    R832416C001 (Final)
    R827353 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: IJE-Full Text HTML
    Exit
  • Other: IJE-Full Text PDF
    Exit
  • 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, cardiovascular vulnerability, automobile exhaust, airborne particulate matter, chemical composition, biological mechanisms, biological mechanism , traffic related particulate matter, human exposure, ambient particle health effects, autonomic dysfunction, human health risk

    Progress and Final Reports:

    Original Abstract
  • 2006 Progress Report
  • 2007 Progress Report
  • 2008 Progress Report
  • 2009 Progress Report
  • 2010 Progress Report

  • Main Center Abstract and Reports:

    R832416    Harvard Particle Center

    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