Grantee Research Project Results
Final Report: Cardiovascular Responses to Particulate Air Pollution
EPA Grant Number: R827994Title: Cardiovascular Responses to Particulate Air Pollution
Investigators: Liao, Duanping , Whitsel, Eric , Heiss, Gerardo , Lin, Hung-Mo , Duan, Yinkang
Institution: Pennsylvania State University
EPA Project Officer: Chung, Serena
Project Period: (Extended to April 30, 2004)
Project Amount: $607,630
RFA: Airborne Particulate Matter Health Effects (1999) RFA Text | Recipients Lists
Research Category: Particulate Matter , Air Quality and Air Toxics , Air , Human Health
Objective:
The objectives of this research project were to:
1. Abstract and create, from the U.S. Environmental Protection Agency (EPA) Aerometric Information Retrieval System (AIRS), the average exposures to ambient criteria pollutants for the 15,792 individuals who participated in the Atherosclerosis Risk in Communities (ARIC) study, as 1-day, 2-day, 3-day, and/or 6-day averages prior to their randomly scheduled cohort clinical examinations (baseline in 1987-1989 and fourth exam in 1996-1998).
2. Combine the air pollution data with the cardiovascular health data already collected by the ARIC investigators to study:
(a) The independent relationships between exposure to criteria pollutants and:
· cardiac autonomic control assessed by heart rate variability (HRV),
· cardiovascular reactivity assessed by postural changes of blood pressure and heart rate,
· inflammatory/hemostatic markers, and
· the presence of arrhythmias assessed by 2-minute electrocardiogram rhythm strips.
(b) The relationships between criteria pollutants and validated cardiovascular diseases (CVD), including sudden cardiac death, myocardial infarction (MI), coronary heart disease (CHD), and stroke.
Summary/Accomplishments (Outputs/Outcomes):
The major accomplishments under this grant include: (1) derived and cleaned air pollution data (PM10, O3, SO2, NO2, and CO) from EPA’s AIRS database; (2) for each of the 15, 792 study participants, calculated exposures to each pollutant 1 day, 2 days, and 3 days prior to their clinical examinations from which the clinical and sub-clinical CVD variables were measure; (3) impaired cardiac repolarization; (4) merged the exposure data with the clinical and sub-clinical outcome variables, and with individual co-variables; (5) completed statistical analyses for all the research hypotheses; and (6) prepared manuscripts summarizing the study results that have been published or accepted for publication, or are in review at different levels.
Source PopulationStudy subjects were selected from the ARIC study cohort. The design and objectives of the ARIC study have been reported in detail (ARIC Investigators, 1989). Briefly, ARIC is a population-based longitudinal study of atherosclerosis and its sequelae sponsored by the National Heart, Lung, and Blood Institute. The ARIC cohort was selected as a probability sample of 15,792 men and women between the ages of 45-64 years at entry from four study centers in the United States, three of which enumerated and enrolled populations reflective of their respective ethnic composition (Washington County, Maryland; ; Forsyth County, North Carolina, and selected suburbs of Minneapolis, Minnesota). The fourth quarter of the ARIC cohort was sampled from African American residents of Jackson, Mississippi. Eligible participants were interviewed at home, and then invited to a baseline clinical examination (conducted in 1987-1989). The date for the baseline clinical examination was assigned at random. The cohort underwent three follow-up clinical examinations every 3 years after baseline. The follow-up examinations were scheduled according to the anniversary of the baseline examination. Of the 15,792 cohort members inducted during the baseline survey, 27 percent were African American.
Air Pollution and Meteorological DataWe abstracted criteria pollutants data for the four ARIC study field centers between 1996 and 1998 from EPA’s AIRS database. AIRS is a computer-based repository of information about airborne pollution in the United States. The AIRS system is administered by the EPA Office of Air Quality Planning and Standards, Information Transfer and Program Integration Division. AIRS databases are maintained and updated by EPA, and the databases are physically stored in a network of computers in EPA facilities in North Carolina. The AIRS database contains measurements of ambient concentrations of air pollutants from thousands of monitoring stations operated by EPA, states, or local agencies. These monitoring sites conform to uniform criteria of site selection, instrumentation, and quality assurance. The directly measured daily ambient air pollution data were sent to the AIRS system for storage and analysis. The AIRS database also contains descriptive information about each monitoring station, including its location and operator. The gaseous pollutant data obtained from the AIRS database were hourly monitor-specific measures. From these hourly monitor-specific measures, monitor-specific daily average concentrations were calculated as either the 8-hour average (1000 to 1800 hours) for O3, or 24-hour averages for CO, SO2, and NO2. The PM10 data obtained from the AIRS database were monitor-specific daily (24-hour) averages. From these monitor-specific daily averages, county specific-daily average (CSDA) pollutant exposures were calculated for each pollutant by averaging all available monitor-specific daily averages from all operating monitors within a county on any calendar date.
From the National Weather Center, we obtained data on relative humidity (in percent), temperature (in degrees K), and sky cloud cover (the fraction of the celestial dome covered by clouds on a scale from 0 to 10, where 0 indicated very clear and 10 indicated a totally obscured sky), with calendar date and county/state identifiable. In this report, the “daily meteorological variables” were defined as the relative humidity, temperature, and sky cloud cover in the county at 1400 hours.
Major Results From This StudyShort-Term Ambient Air Pollution Exposures and Impaired Cardiac Autonomic Control. We performed a cross-sectional study to investigate this important association. In this study, we identified statistically significant associations between higher levels of criteria pollutants and lower HRV and higher heart rate in a population-based sample. Some associations were more pronounced in persons with a history of CVD or hypertension. These findings highlight a putative mechanism through which air pollution is associated with CVD mortality. Table 1 below summarizes the key findings from this study.
Table 1. Multivariable# Adjusted Regression Coefficients (SE) of HRV Indices per One Standard Deviation (SD) Increment of PM10 Concentrations Measured 1 day, 2 days, and 3 days Prior to HRV Measurement.
PM10 Measured at Different Times Prior to HRV Measurement |
|||||||||
One Day Prior |
Two Days Prior |
Three Days Prior |
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b |
SE |
P value |
b |
SE |
P value |
b |
SE |
P value |
|
Ln HF (msec2) |
-0.093 |
0.028 |
<0.001 |
0.005 |
0.033 |
0.883 |
-0.004 |
0.028 |
0.893 |
Ln LF (msec2) |
-0.078 |
0.028 |
0.005 |
0.048 |
0.033 |
0.144 |
-0.021 |
0.028 |
0.439 |
SDNN (msec) |
-1.746 |
0.468 |
<0.001 |
0.713 |
0.556 |
0.199 |
-0.212 |
0.469 |
0.651 |
HR (beat/min.) |
0.474 |
0.238 |
0.047 |
-0.320 |
0.283 |
0.258 |
-0.221 |
0.239 |
0.355 |
Short-Term Ambient Air Pollution Exposures and QT Prolongation. We tested the short-term associations of criteria pollutants (PM10, O3, CO, NO2, and SO2) and QT prolongation as measured by heart rate corrected QT Index in the ARIC study population. We found that higher criteria pollutant concentrations were associated with prolonged ventricular repolarization. The associations were more pronounced in persons with a history of CHD, diabetes, and hypertension. Table 2 below summarizes the key findings from this project.
Table 2. Multivariable Adjusted* Regression Coefficient (SE) of QTI per One SD Increment of PM10
b |
SE |
P value |
||
PM10 (12.4μg/m3) |
All |
0.15 |
0.06 |
<0.05 |
HYP* = Yes |
0.24 |
0.08 |
<0.01 |
|
HYP* = No |
-0.06 |
0.11 |
0.630 |
HYP = Hypertension
Short-Term Air Pollution Exposures and Systemic Inflammation and Blood Coagulation. We investigated the short-term associations of criteria pollutants (PM10, O3, CO, NO2, and SO2) with blood markers of systemic inflammation and blood coagulation, which are well established risk markers and risk factors for acute MI. Relevant to this proposal, we observed consistent associations between air pollution and several markers of systemic inflammation and blood coagulation. The main results are summarized in Table 3.
Table 3. Multivariable Adjusted# Regression Coefficients (SE) for the Associations Between One SD Increment of PM10 (12.8 μg/m3) and Markers of Inflammation and Coagulation
Pollutant |
Dependent Variable |
||||
Fibrinogen (mg/dL) |
Factor |
vWF (%) |
WBC |
Albumin (g/dL) |
|
PM10 |
0.163 (0.755) |
See |
Diabetics: 3.93 (1.80)* |
0.021 (0.019) |
CVD: -0.006 (0.003)* |
* p < 0.05 ** p < 0.01
Short-Term Air Pollution Exposures and Blood Pressure and Its Reactivity. In the ARIC study population, we investigated the short-term associations of criteria pollutants (PM10, O3, CO, NO2, and SO2) with blood pressure and its reactivity to postural change; both are risk factors for CVD and hypertension, and the latter also is a marker of autonomic balance and baroreflector sensitivity. Relevant to this study, we observed consistent associations between air pollution and seated blood pressures (seated systolic blood pressure [SBP], diastolic blood pressure [DBP], and pulse pressure [PP]). The main results are summarized in Table 4.
Table 4. Multivariable# Adjusted Regression Coefficients (SE) of BP Associated With One SD Increment of PM10 |
|||
SBP (mmHg) |
DBP (mmHg) |
PP (mmHg) |
|
PM10 (SD=12.4 μg/m3) Diabetics |
0.09 (0.23) 0.74 (0.41) * 1.91 (0.83) * |
- 0.02 (0.14) N/A N/A |
0.12 (0.18) N/A 1.35 (0.65) * |
# Adjusted for age, smoking, alcohol consumption, body mass index, prevalent CHD, chronic respiratory disease, hypertension, and diabetes (when appropriate), as well as demographic and socioeconomic variables (ethnicity, center, sex, and education). |
|||
Significant Implication From This Study
As listed in the abstracts and manuscripts derived from this grant, we demonstrated that criteria pollutants (PM10, SO2, NO2, CO, and O3) are significantly associated with the following markers of CVD risk factors: (1) higher plasma hemostatic/inflammatory markers; (2) impaired cardiac autonomic control; (3) impaired cardiovascular reactivity; (4) impaired cardiac repolarization; and (5) higher blood pressure. There is a lack of significant association between criteria pollutants and clinical arrhythmia.
These results are supportive of three potential underlying mechanisms through which short-term increases of air pollutants may affect cardiovascular health: (1) systemic inflammation and blood coagulation; (2) cardiac autonomic balance, reflected by lower HRV and QT prolongation; and (3) impaired baroreceptor sensitivity, reflected as increased BP levels and BP-reactivity.
Results from this large population-based study, which to our knowledge is the first in this field, suggest that higher levels of PM10, O3, CO, NO2, and SO2, even at levels far below the current EPA standards, have adverse health effects on the cardiac system. When comparing the regression coefficients from each individual pollutant model, the effect size for PM10 is much stronger than that for gaseous pollutants.
Most of the associations we obtained are generally “weak” compared to other traditional CVD risk factors. From the etiologic perspective, the weak associations suggest that these pollutants are minor risk factors for CVD. From the public health perspective, however, it can be argued that controlling air pollution could have a significant public health impact because the pollutant levels were derived as daily averages from ambient air monitors in different locations in the United States, and thus, even a “high” level of exposure in this study is reflective of environmentally relevant low ambient exposure levels to which the entire population is exposed on a daily basis.
Our data also suggest significant effect modifications by existing cardiovascular conditions (by hypertension, prevalent CHD, and diabetes). Such effect modifications, if confirmed by other studies, are suggestive of differential susceptibility to pollutant exposures.
Lagged analysis in our data indicate that pollutant concentrations, measured 2 or 3 days prior to outcome assessments, were not significantly associated with analyzed cardiac outcomes. Furthermore, adjusting for 2-day and 3-day exposures simultaneously did not change the pattern of associations in relation to a 1-day exposure prior to outcome measures. These results are consistent with our previous findings, are indicative of an acute effect of PM10 on the cardiac system, and may suggest that air pollution is more likely to act as a triggering factor for cardiac disease.
Journal Articles on this Report : 3 Displayed | Download in RIS Format
Other project views: | All 14 publications | 3 publications in selected types | All 3 journal articles |
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Type | Citation | ||
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Liao D, Duan Y, Whitsel EA, Zheng Z-j, Heiss G, Chinchilli VM, Lin H-M. Association of higher levels of ambient criteria pollutants with impaired cardiac autonomic control: a population-based study. American Journal of Epidemiology 2004;159(8):768-777. |
R827994 (Final) |
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Liao D, Heiss G, Chinchilli VM, Duan Y, Folsom AR, Lin H-M, Salomaa V. Association of criteria pollutants with plasma hemostatic/inflammatory markers: a population-based study. Journal of Exposure Analysis and Environmental Epidemiology 2005;15(4):319-328. |
R827994 (Final) |
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Xie SX, Liao D, Chinchilli VM. Measurement error reduction using weighted average method for repeated measurements from heterogeneous instruments. Environmetrics 2001;12(8):785-790. |
R827994 (2001) R827994 (Final) |
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Supplemental Keywords:
population-based study, public health, air pollution, ambient air, particulate matters, ozone, heart disease, health effects, heart rate variability, inflammation, blood coagulation, epidemiology,, RFA, Scientific Discipline, Health, Air, particulate matter, Environmental Chemistry, Health Risk Assessment, Epidemiology, Risk Assessments, Biochemistry, Atmospheric Sciences, Biology, ambient aerosol, copollutant exposures, particulates, air toxics, cardiopulmonary responses, human health effects, cardiovascular vulnerability, heart rate variability, air pollution, chronic health effects, particulate exposure, ethnicity, Acute health effects, blood pressure, PM, cardiotoxicity, myocardium infarction, cardiac arrhythmiasRelevant Websites:
http://www.personal.psu.edu/faculty/d/x/dxl32/ Exit
Progress and Final Reports:
Original AbstractThe 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.