Final Report: Cardiovascular Vulnerability to Particulate Pollution

EPA Grant Number: R826780
Title: Cardiovascular Vulnerability to Particulate Pollution
Investigators:
Institution: Harvard T.H. Chan School of Public Health
EPA Project Officer: Chung, Serena
Project Period: October 1, 1998 through September 30, 2001
Project Amount: $648,227
RFA: Health Effects of Particulate Matter and Associated Air Pollutants (1998) RFA Text |  Recipients Lists
Research Category: Air Quality and Air Toxics , Health Effects , Air , Particulate Matter

Objective:

The objective of this research project was to define the effect of ambient pollution on heart rate variability (HRV), arrhythmias, ST-segment changes, blood pressure, oxygen saturation, and airway inflammation as measured by exhaled nitric oxide (NO). We also explored the relative contribution of a variety of pollutants on these outcomes and the subject characteristics that lead to sensitivity to pollution effects on the cardiorespiratory system. Moreover, we assessed the relationship between lung inflammation as measured by exhaled NO and the cardiac response to particle pollution. Although the funding period has ended, we are continuing to explore additional aspects of these data to determine whether antioxidants have any protective effect against the cardiac effects of particles. The results will be useful in understanding mechanisms leading to the observed association between particle pollution and adverse cardiac effects.

Summary/Accomplishments (Outputs/Outcomes):

In susceptible adults, we proposed to examine whether fine particle (PM2.5) exposure results in similar changes in cardiovascular function as reflected in changes in blood pressure, heart rate, heart rate regularity, and electrocardiogram (ECG) intervals and morphology, particularly in measures of myocardial conductance, repolarization, and irritability. Specifically, we proposed a time series epidemiologic study involving repeated monitoring of adults to evaluate whether measures of cardiovascular function vary as air pollution varies. In Boston, of 38 active adults 60 to 90 years of age who were screened from March-May 1998 for study eligibility, 27 were selected to participate in the community-based panel. These participants were evaluated from June-September 1999, during the summer periods. Once per week for 12 weeks, the participants answered a questionnaire regarding cardiac and respiratory symptoms and changes in medication use. They received ECG Holter monitoring for a 25-minute period involving 5 minutes of rest supine, 5 minutes of standing upright, 5 minutes of exercise, 5 minutes of recovery, and 5 minutes of slow breathing. Supine, upright, and post-exercise blood pressure, continuous heart rate, and oximetry also were monitored. Continuous measures of outdoor PM2.5, O3, and CO were performed at a nearby monitoring site and indoors at the testing site during testing hours. Questionnaire data were entered and verified. Electrophysiologic outcomes of interest include ECG repolarization abnormalities, ventricular premature beats, measures of HRV, PR and QT intervals, oxygen saturation, and blood pressure. Through work by Dr. Bruce Nearing in concert with Drs. Verrier, Stone, and Gold, programs were developed for the reading of the Holter Monitor data to summarize time domain and frequency domain heart rate variability outcomes and ST-segment changes.

In Steubenville, Ohio, active adults 60 to 90 years of age were screened from March-May 1999 for study eligibility, and 30 were selected to participate in the community-based panel. These participants were evaluated from June-December 2000, during the summer, fall, and winter periods, using the same protocol as in the previous summer. The Steubenville study included additional measures of indoor home exposure and personal exposure to particles. The study also included additional measures of post-exercise blood pressure and exhaled NO. Data analyses from the Boston study show associations between particle pollution (especially black carbon) and reduced HRV. Reduced HRV suggests pollution-related autonomic dysfunction. In other studies, reduced HRV has been shown to be a predictor of sudden cardiac death. In the Boston 1999 study, particle pollution also was associated with a small reduction in oxygen saturation. Recently, preliminary analyses suggest that ST segment depression also is associated with increased black carbon levels in that Boston 1999 study. In Steubenville, higher particle levels predict higher levels of exhaled NO, a measure of airway inflammation. Future analyses of Steubenville data will investigate the relation of indoor and outdoor pollution to HRV and the other outcomes investigated in the Boston setting. Pilot work by junior investigators, the testing of additional hypotheses, and the collection and analysis of additional data in the Boston and the Steubenville studies have been supported by additional U.S. Environmental Protection Agency (EPA) and National Institute of Environmental Health Sciences (NIEHS) funding (EPA R821762, EPA R82353, NIEHS ES0629, and ES 09825).

We conclude that we are beginning to see a relationship of particle pollution to multiple outcomes related to pulmonary (lung airway) inflammation, very mildly reduced oxygen saturation in the blood, autononomic dysfunction that may predispose sensitive individuals to heart arrhythmias, and other EKG changes. Our findings may partly explain why, in large epidemiologic studies, particle pollution predicts hospitalization and death due to cardiac events.

Technical Aspects/Computer Modeling

We investigated the associations between ambient pollution levels and HRV in a repeated measures study of elderly Boston residents, and published our study results in Circulation. In that published article, we presented results from random effects analyses that did not utilize generalized additive models, demonstrating our ability to replicate our main findings derived from generalized additive models. To address any further concerns regarding secondary results from generalized additive models that might use inadequate default convergence criteria and/or have variance estimation issues, we performed a comprehensive reanalysis of our study and found no significant differences in the estimates of the effects of ambient pollution (PM2.5 or O3) on HRV. Technical aspects related to processing of the Holter Monitoring data and air pollution exposure data are contained in a manuscript and in the original article published in Circulation.

In brief, a trained engineer used a Marquette MARS Workstation to review and, when necessary, correct automatically determined readings of QRS complexes. Regions of noise and artifact (<1 percent of data) were eliminated. After correction, software facilities on the MARS were used to export beat timing and annotation information for analysis and creation of outcome variables through custom PC-based software written in the C language. Only normal-to-normal (NN) intervals between 150 and 5,000 ms with NN ratios between 0.8 and 1.2 were included for analysis of HRV. No tape contained >1 percent premature beats.

Two time domain measures of HRV were obtained. The standard deviation of normal RR intervals (SDNN) and the square root of the mean of the squared differences between adjacent normal RR intervals (r-MSSD) were calculated from all normal RR intervals for each portion of the protocol and overall.

Airborne particles with an aerodynamic diameter equal to or less than 2.5 and 10 micrometers (PM2.5, PM10) were measured continuously 6 km from the study site, using the Model 1400A Tapered Element Oscillating Microbalance (TEOM). Because the TEOM sample filter is heated to 50°C, a season specific correction was used to compensate for the loss of semivolatile mass that occurs at this temperature. Calibration factors were obtained by regressing continuous PM2.5 and PM10 concentrations averaged over 24-hour periods on the corresponding collocated integrated 24-hour Harvard Impactor low-volume Teflon filter gravimetric measurements:

corrected PM2.5 = (measured PM2.5 + 2.00) ) 0.944 for May through August, r2 = 0.99.

Coarse matter was calculated by subtracting PM2.5 from PM10. Continuous carbon monoxide data were collected within a quarter of a mile of the participant residence, with a ThermoEnvironmental (Franklin, MA) Model 48 gas analyzer using an EPA reference method. Ozone, NO2, SO2, temperature, and relative humidity measurements were obtained from the Massachusetts Department of Environmental Protection local monitoring site, located 4.8 miles from the study site.


Journal Articles on this Report : 10 Displayed | Download in RIS Format

Other project views: All 15 publications 11 publications in selected types All 10 journal articles
Type Citation Project Document Sources
Journal Article Adamkiewicz G, Ebelt S, Syring M, Slater J, Speizer FE, Schwartz J, Suh H, Gold DR. Association between air pollution exposure and exhaled nitric oxide in an elderly population. Thorax 2004;59(3):204-209. R826780 (Final)
R827353 (Final)
R827353C003 (Final)
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  • Journal Article DeMeo DL, Zanobetti A, Litonjua AA, Coull BA, Schwartz J, Gold DR. Ambient air pollution and oxygen saturation. American Journal of Respiratory and Critical Care Medicine 2004;170(4):383-387. R826780 (Final)
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  • Journal Article Gold DR, Litonjua A, Schwartz J, Lovett E, Larson A, Nearing B, Allen G, Verrier M, Cherry R, Verrier R. Ambient pollution and heart rate variability. Circulation 2000;101(11):1267-1273. R826780 (Final)
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  • Journal Article Gold DR, Litonjua AA, Zanobetti A, Coull BA, Schwartz J, MacCallum G, Verrier RL, Nearing BD, Canner MJ, Suh H, Stone PH. Air pollution and ST-segment depression in elderly subjects. Environmental Health Perspectives 2005;113(7):883-887. R826780 (Final)
    R827353 (Final)
    R827353C003 (Final)
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  • Journal Article Luttmann-Gibson H, Suh HH, Coull BA, Dockery DW, Sarnat SE, Schwartz J, Stone PH, Gold DR. Short-term effects of air pollution on heart rate variability in senior adults in Steubenville, Ohio. Journal of Occupational and Environmental Medicine 2006;48(8):780-788. R826780 (Final)
    R827353 (Final)
    R827353C003 (Final)
    R832416 (2008)
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  • Journal Article Sarnat SE, Coull BA, Schwartz J, Gold DR, Suh HH. Factors affecting the association between ambient concentrations and personal exposures to particles and gases. Environmental Health Perspectives 2006;114(5):649-654. R826780 (Final)
    R827353 (Final)
    R827353C001 (Final)
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  • Journal Article Sarnat SE, Suh HH, Coull BA, Schwartz J, Stone PH, Gold DR. Ambient particulate air pollution and cardiac arrhythmia in a panel of older adults in Steubenville, Ohio. Occupational and Environmental Medicine 2006;63(10):700-706. R826780 (Final)
    R827353 (Final)
    R827353C003 (Final)
    R832416 (2008)
    R834797 (2016)
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  • Journal Article Schwartz J, Litonjua A, Suh H, Verrier M, Zanobetti A, Syring M, Nearing B, Verrier R, Stone P, MacCallum G, Speizer F, Gold DR. Traffic related pollution and heart rate variability in a panel of elderly subjects. Thorax 2005;60(6):455-461. R826780 (Final)
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  • Journal Article Timonen KL, Vanninen E, de Hartog J, Ibald-Mulli A, Brunekreef B, Gold DR, Heinrich J, Hoek G, Lanki T, Peters A, Tarkiainen T, Tittanen P, Kreyling W, Pekkanen J. Effects of ultrafine and fine particulate and gaseous air pollution on cardiac autonomic control in subjects with coronary artery disease:the ULTRA study. Journal of Exposure Science and Environmental Epidemiology 2006;16(4):332-341. R826780 (Final)
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  • Journal Article Zanobetti A, Canner MJ, Stone PH, Schwartz J, Sher D, Eagan-Bengston E, Gates KA, Hartley LH, Suh H, Gold DR. Ambient pollution and blood pressure in cardiac rehabilitation patients. Circulation 2004;110(15):2184-2189. R826780 (Final)
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  • Supplemental Keywords:

    ambient air, particulates, ozone, elderly, Northeast., RFA, Health, Scientific Discipline, Air, Geographic Area, particulate matter, air toxics, Health Risk Assessment, Epidemiology, State, Risk Assessments, Disease & Cumulative Effects, Biochemistry, tropospheric ozone, Atmospheric Sciences, ambient aerosol, particle size, cardiac arrhythmia, health effects, particulates, cardiopulmonary responses, fine particles, human health effects, PM 2.5, air pollutants, effects assessment, exposure and effects, cardiovascular vulnerability, heart rate variability, ozone, air pollution, Massachusetts (MA), chronic health effects, human exposure, particulate exposure, Acute health effects, ambient particulates, environmental stressors, harmful environmental agents, blood pressure, mortality, hyperadrenergic, cardiac arrhythmias, exposure assessment, heart rate

    Progress and Final Reports:

    Original Abstract
  • 1999 Progress Report
  • 2000 Progress Report