Grantee Research Project Results
2006 Progress 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 , Boston University
Current Institution: Harvard University
EPA Project Officer: Chung, Serena
Project Period: October 1, 2005 through September 30, 2010 (Extended to September 30, 2011)
Project Period Covered by this Report: October 1, 2005 through September 30, 2006
RFA: Particulate Matter Research Centers (2004) RFA Text | Recipients Lists
Research Category: Human Health , Air
Objective:
In our original U.S. Environmental Protection Agency (EPA)-funded Particle Center, 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 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 suggest 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.
In Project 1 of our new Center, we are continuing our analysis of 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 will include ECG, blood inflammatory marker, medication, genotype, food frequency, and particle exposure measurements for each of the current NAS participants. ECG and blood samples are being analyzed for a variety of measures (HRV, ST segments, QT intervals, CRP, sICAM-1, sVCAM-1, and homocysteine); these measures will be used as intermediate markers of the inflammatory, endothelial, and autonomic pathways. In addition, they will be related to individual-specific indoor PM2.5, SO42-, and BC exposures that are being measured for one week 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 are being measured at our stationary ambient monitoring (SAM) site. The study will use these data to test three primary hypotheses.
Hypothesis 1
Cardiovascular effects of particles (PM) will 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 heart rate variability (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 will be 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.
Progress Summary:
In Year One, we have continued to collect ECG measurements on the Normative Aging Study participants. In addition, we have begun to collect daily diet information during each clinic visit using a validated semi-quantitative food frequency questionnaire. To date, we already have data from enough participants to begin fitting longitudinal models. During Year Two of the Center, we expect to continue these analyses using data for an additional 100 participants. We have also genotyped the participants for the micro-satellite repeat of HMOX-1, and have started to look at these data.
Analyses are underway to examine the modifying effect of lead burden on the association between PM and HRV, the modifying effects of HFE genotypes on that association, and the association between air pollution and homocysteine concentrations. Other analyses of ambient air pollution and health for the NAS cohort have been completed and are currently in press in peer-reviewed journals.
We have constructed and validated an integrated particle sampler to measure one-week long indoor particle concentrations (Figure 1). Correspondingly, participant-friendly mailers, sampling instructions, and sampling logs were developed to allow these samplers to be mailed to study participants, in order for participants to install, operate, and return these samplers to the health clinic.
We are currently recruiting participants for exposure sampling. By September 2006, twenty NAS participants had received and completed indoor particle exposure sampling. These individuals were identified through telephone calls made approximately two weeks prior to their clinic visit. Sampling units were prepared in the laboratory, with the installation of a pre-weighed Teflon® filter and an initial flow measurement. Participants volunteering for indoor exposure monitoring were mailed samplers, together with corresponding instructions and sampling logs, for receipt one-week prior to their clinic visit. After receipt, participants removed samplers from the boxes and plugged samplers into an electrical outlet in the main activity room of their home. Participants unplugged samplers and brought samplers with them to the health visit. Samplers were then returned to the central laboratory for analysis, whereupon a final flow measurement was taken, and the filter was removed for future analysis (gravimetric, reflectance, and ion chromatographic analysis).
Figure 1. Indoor Particle Exposure Sampler—Outside and Inside Views
Future Activities:
Health and exposure data collection is on-going, as is laboratory and statistical analyses of collected samples. HRV tapes are currently been analyzed for additional HRV measures, including QT length. Using funds redirected from Project 2, health and pollution measurements for our NAS cohort will continue for the duration of the Center. In addition, we will supplement these measurements with 8-OHdG in urine, a marker for oxidative stress.
Journal Articles:
No journal articles submitted with this report: View all 68 publications for this subprojectSupplemental Keywords:
air pollution, indoor monitoring, inflammation, heart rate variability, spatio-temporal air pollution modeling,, 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 stressRelevant Websites:
http://www.hsph.harvard.edu/epacenter Exit
Progress 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
- Final Report
- 2010 Progress Report
- 2009 Progress Report
- 2008 Progress Report
- 2007 Progress Report
- Original Abstract
67 journal articles for this subproject
Main Center: R832416
206 publications for this center
199 journal articles for this center