Air Pollution Effects on Ventricular Repolarization

EPA Grant Number: R832347C141
Subproject: this is subproject number 141 , established and managed by the Center Director under grant R832347
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Health Effects Institute (2005 — 2010)
Center Director: Greenbaum, Daniel S.
Title: Air Pollution Effects on Ventricular Repolarization
Investigators: Lux, Robert L
Institution: Health Effects Institute , Desert Research Institue , Michigan State University , University of Medicine and Dentistry of New Jersey , University of Utah
EPA Project Officer: Hunt, Sherri
Project Period: April 1, 2005 through March 31, 2010
RFA: Health Effects Institute (2010) RFA Text |  Recipients Lists
Research Category: Health Effects , Air


Epidemiologic studies have described an association between increases in cardiovascular morbidity and mortality and increases in ambient particulate matter (PM) concentrations, especially in susceptible populations such as the elderly and persons with pulmonary or cardiovascular disease. However, the biological mechanisms by which PM and other air pollutants may affect cardiovascular events are not well understood. Several studies have shown that air pollution may be associated with cardiac outcomes such as arrhythmias, suggesting that air pollutants may affect autonomic control of the heart.

Heart rate variability (HRV) is an electrophysiologic parameter that can be derived from an electrocardiogram (ECG). Low HRV is a marker of poor cardiac autonomic control and is associated with a higher risk of myocardial infarction and sudden cardiac death. Several cohort and panel studies have shown that increases in ambient PM concentrations are associated with decreased HRV, although it remains unclear how decreased HRV contributes to cardiac arrhythmia. Thus, the evaluation of additional ECG parameters, such as v entricular repolarization — the process of electrical recovery of the heart cells after contraction of the ventricles — is warranted.

Robert Lux of the University of Utah and Arden Pope of Brigham Young University proposed to study the association between air pollution and ventricular repolarization, using a novel approach developed by Dr. Lux to analyze ECG data previously collected by Dr. Pope. HEI funded the study because it considered the proposed evaluation of repolarization using novel electrophysiologic parameters to be an interesting approach to studying possible mechanisms underlying PM effects on cardiovascular morbidity and mortality.


Drs. Lux and Pope hypothesize that high levels of ambient PM might affect ventricular repolarization independent of heart rate and that such changes could lead to an increased risk of arrhythmia in elderly persons, who may be more susceptible to the effects of air pollution. They will use the ECG data obtained previously in a study of elderly participants conducted by Dr. Pope, which had shown an association between ambient concentrations of particulate matter less than 2.5 μm in diameter (PM2.5) and decreased HRV. In the current study, the investigators will analyze novel repolarization parameters in ECGs obtained from 61 participants. For each person, the ECG parameters will be compared between days of high and low PM2.5 concentrations. If there were more than 2 recordings for a participant, the ECG obtained on the day with the lowest PM2.5 concentration will serve as the control.

Dr. Lux will use custom software to calculate a root mean square (RMS) ECG, which will capture the magnitude of the ECG wave forms. He then will determine RMS ECG repolarization parameters such as RMS RT interval, RMS width of the T wave, and RMS QT interval, as well as their heart ratecorrected forms. Data will be average over 30- minute periods (“epochs”) and presente a 24-hour time series. Two statistical approaches will be used to evaluate differences between parameters on days with low versus high PM2.5 concentrations: a nonparametric Kolmogorov-Smirnov test and within-subject regression modeling. Fifty-two participants will be included in the Kolmogorov-Smirnov analysis; 61 participants will be included in the regression modeling.

Main Center Abstract and Reports:

R832347    Health Effects Institute (2005 — 2010)

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R832347C135 Mechanisms of Particulate Matter Toxicity in Neonatal and Young Adult Rat Lungs
R832347C136 Uptake and Inflammatory Effects of Nanoparticles in a Human Vascular Endothelial Cell Line
R832347C138 Health Effects of Real-World Exposure to Diesel Exhaust in Persons with Asthma
R832347C140 Extended Follow-Up and Spatial Analysis of the American Cancer Society Study Linking Particulate Air Pollution and Mortality
R832347C141 Air Pollution Effects on Ventricular Repolarization
R832347C143 Measurement and Modeling of Exposure to Selected Air Toxics for Health Effects Studies and Verification by Biomarkers
R832347C144 Genotoxicity of 1,3-Butadiene and Its Epoxy Intermediates
R832347C145 Effects of Concentrated Ambient Particles and Diesel Emissions on Rat Airways
R832347C147 Atmospheric Transformation of Diesel Emissions