Final Report: Epidemiologic Study of Particulate Matter and Cardiopulmonary Mortality

EPA Grant Number: R827355C001
Subproject: this is subproject number 001 , established and managed by the Center Director under grant R827355
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Airborne PM - Northwest Research Center for Particulate Air Pollution and Health
Center Director: Koenig, Jane Q.
Title: Epidemiologic Study of Particulate Matter and Cardiopulmonary Mortality
Investigators: Kaufman, Joel D. , Ishikawa, Naomi , Karr, Catharine J. , Miller, Kristine , Schreuder, Astrid , Shepherd, Kristine , Sheppard, Lianne (Elizabeth) A. , Siscovick, David , Sullivan, Jeff
Institution: University of Washington
EPA Project Officer: Chung, Serena
Project Period: June 1, 1999 through May 31, 2004 (Extended to May 31, 2006)
Project Amount: Refer to main center abstract for funding details.
RFA: Airborne Particulate Matter (PM) Centers (1999) RFA Text |  Recipients Lists
Research Category: Air Quality and Air Toxics , Particulate Matter , Air

Objective:

The objective of Years 1-3 of this research project was to investigate associations between ambient particulate matter (PM) exposure and cardiopulmonary disease risks. The objective was addressed mainly through the use of case-crossover study designs. In Years 4-6 of the project, the epidemiology research objectives were expanded to consider myocardial infarction (MI) onset in Seattle and PM-health outcomes in the multi-city setting of the Women’s Health Initiative (WHI).

Summary/Accomplishments (Outputs/Outcomes):

Project 1-1. Acute Effects of PM Using Case-Crossover Methods

We used the time-stratified bi-directional case-crossover method to assess the effects of PM on out-of-hospital sudden cardiac arrest and on the triggering of MI onset in community-based studies in Puget Sound.

1-1a—Sudden Cardiac Arrest. We studied the association between the incidence of primary cardiac arrest (PCA) and daily measures of fine PM using a case-crossover study of 1,206 cases of out-of-hospital cardiac arrest in individuals with (n=774) and without (n=432) clinically recognized heart disease. We compared PM levels measured by nephelometry on event days and the 2 days preceding the event with PM levels from matched reference days. The estimated relative risk for a 13.8 μg/m3 increase in fine PM (nephelometry [0.54 × 10-1 km-1 bsp]) the day before PCA was 0.94 (95% CI: 0.88-1.02). Analyses of pollutant levels measured on the same day as the event and 2 days preceding event demonstrated similar results. No increased risk was found in all cases with pre-existing cardiac disease (OR 0.97 [95% CI: 0.89, 1.07]); an unexpected association, however, appeared in current smokers with pre-existing heart disease and increased PM levels 2 days before the event (OR 1.29 [95% CI: 1.06, 1.55]). This association was not present in the 0-day or 1-day lag analyses or in individuals with other diseases.

Conclusion

There was no consistent association between an increase in fine PM and risk of PCA in those with and without clinically recognized heart disease.

1-1b—Myocardial Infarction Triage and Intervention Study. The Myocardial Infarction Triage and Intervention (MITI) study analyses refined our initial outcome to include only those individuals with a confirmed case of MI. The analyses addressed the issue of very short-term effects of PM on the triggering of MI by modeling effects of 1-hour and 4-hour exposure. We studied the association between onset time of MI and preceding hourly measures of fine PM using a case-crossover study of 5,793 confirmed cases of acute MI. We linked data from a community-wide acute MI database from 1988-1994 in King County, Washington, with central-site air pollution monitoring data on fine PM determined by nephelometry. We compared air pollution exposure levels averaged 1-hour, 2-hours, 4-hours, and 24-hours prior to MI onset time to a set of time-stratified referent exposures from the same day of the week in the month of the case event. The estimated relative risk for a 10 μg/m3 increase in fine PM the hour prior to MI onset was 1.01 (95% CI: 0.98-1.05). Analyses of pollutant levels averaged 2-hours, 4-hours, and 24-hours preceding event demonstrated a similar lack of association. No increased risk was found in all cases with pre-existing cardiac disease (OR 1.05 [95% CI: 0.95, 1.16]). Stratification by known cardiovascular risk factors (hypertension, diabetes, and smoking status) also did not modify the relation between fine PM and MI onset.

Conclusion

Although a very small effect cannot be excluded, there was no consistent association between ambient levels of fine PM and risk of MI onset.

Project 1-2. Panel Study Health Effects

This study investigated the effects of PM on blood measures of inflammation and thrombosis in an elderly population. The potential subclinical health effects of PM that lead to the increased risk of cardiovascular events were addressed. We explored the following two major hypotheses of PM effect on cardiovascular function: (1) acute PM exposure results in altered levels of systemic inflammation and a pro-thrombotic state; and (2) increased PM results in altered autonomic regulation of heart rate control as measured by heart rate variability measures.

1-2a—Systemic Inflammation and Thrombosis. We postulated that elevated levels of PM would be associated with increased blood levels of inflammatory and thrombotic markers in elderly individuals. We also hypothesized that elevated PM would increase levels of cytokines in individuals with heart disease. We measured these blood markers in 47 elderly individuals with (23) and without (16 with chronic obstructive pulmonary disease and 8 healthy) cardiovascular disease (CVD) on 2 or 3 mornings over a 5 or 10-day period between February 2000 and March 2002. Blood measures were paired with residence level outdoor PM measured by nephelometry. Analyses determined the within-individual effect of 24-hour averaged outdoor PM on blood measures. Analyses found no statistically significant effect of a same day 10 μg/m3 increase in fine PM on log transformed levels of C-reactive protein (CRP) 1.21 fold-rise [95% CI: 0.86, 1.70], fibrinogen 1.02 fold-rise [95% CI: 0.98, 1.06], or D-dimer 1.02 fold-rise [95% CI: 0.88, 1.17] in individuals with CVD. One-day lagged analyses in the CVD subgroup found similar null results. These same models found no change in these blood markers at the same-day or 1-day lag in the group without CVD. In 21 individuals with CVD, a 10 μg/m3 increase in same-day PM was associated with a 1.3 fold-rise [95% CI: 1.1, 1.7] in the level of monocyte chemoattractant protein-1.

Conclusion

We did not find consistent effects of low ambient levels of PM on blood measures of inflammation or thrombosis in elderly individuals.

1-2b—Association Between Short-Term Exposure to Fine Particulate Matter and Heart Rate Variability in Older Subjects With and Without Heart Disease. Our hypothesis was that elevations in fine PM measured at the subjects’ homes in the preceding hour would be associated with decreased high frequency heart-rate variability (HF-HRV) in individuals with pre-existing cardiac disease. We collected 285 daily, 20-minute measures of HRV, which included a paced breathing protocol, in the homes of 34 elderly individuals with (21) and without (13) CVD over a 10-day study session in Seattle between February 2000 and March 2002. Fine PM was continuously measured by nephelometry at the individuals’ homes. The overall study population had a median age of 77 (range 57-87), and 44 percent were male. Models that adjusted for health status, relative humidity, temperature, average heart rate, and medication use did not find a significant association between a 10 µg/m3 increase in 1-hour average outdoor PM2.5 preceding HRV measure and change in HF-HRV power in individuals with CVD (3% increase in median HF-HRV [95% CI: -19, 32]) or without CVD (5% decrease in median HF-HRV [95% CI: -34, 36]). Similarly, no association was evident using 4-hour and 24-hour average outdoor PM2.5 exposures prior to HRV measure.

Conclusion

This study did not demonstrate an association between increased residence-level fine PM and frequency domain measures of HRV in elderly individuals.

Project 1-3. Chronic Cardiovascular Effects; Air Pollution and Cardiovascular Disease Events in the Women’s Health Initiative Observational Study (WHI-OS)

The objectives of this study were to: (1) evaluate associations between chronic PM2.5 exposure and incidence of cardiovascular events in the WHI-OS cohort; (2) identify subject characteristics that modify the air pollution associations (suggesting increased susceptibility); and (3) examine within-city compared with between-city effects. Subjects in the air pollution part of this study had no prevalent CD at enrollment, had attended the same clinic since 2002, and lived in a Zip Code less than 30 miles from the centroid. Exposure data were derived from the U.S. Environmental Protection Agency (EPA) AIRS database. Pollutants studied were PM, SO2, nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3). Cardiovascular (CV) outcome events were MI, coronary revascularization, stroke, or CV death. The statistical method used to test for associations was a stratified Cox proportional Hazards regression. The study found a positive association between the time to a first CV event and a 10 μg/m3 increase in PM2.5. The effect was stronger for within-city effects (1.5; 95%CI 1.2, 2.1) than between-city events (1.2; 95%CI: 1.1,1.4). In conclusion, PM2.5 was associated with CV events in post-menopausal women without prior CV disease. Increased risk was observed for overweight and obese women.

Project 1-4. Effect of Ambient Air Pollution on Infant Bronchiolitis

Bronchiolitis is the leading cause of infant hospitalization in the United States and hospitalization rates are rising. Data regarding air pollution’s impact on this disease are few, despite biologic plausibility and evidence linking air pollution to other pediatric respiratory outcomes. This study examined the relationship between infant bronchiolitis hospitalization and ambient levels of CO, NO2, O3, PM10, and PM2.5. Data from birth records linked to first year of life hospitalizations and representative ambient monitors for infants born in the South Coast Air Basin of Southern California in the years 1995-2000 were used. Time-stratified case-crossover methodology was employed to test acute exposure effects. A case-control methodology was used to evaluate similar acute as well as longer term exposure windows. Potential modification of risk for infants born prematurely and with underlying cardiopulmonary disease was investigated. Odds ratios (OR) and 95 percent confidence intervals (CI) were calculated using conditional logistic regression. Potential confounding by meteorologic conditions was addressed in all analyses. In the case control study, potential confounding because of socioeconomic status was performed using available proxy measures.

No increased risk was observed for acute, sub-chronic, and chronic exposure to CO and NO2. O3 effect estimates were generally less than 1.0, suggesting decreased risk. The most consistent positive associations were related to exposure to PM, especially PM2.5. The adjusted ORs (95% CI) for a 10 μg/m3 increase in sub-chronic and chronic exposure were 1.08 (1.05-1.16) and 1.09 (1.04-1.14), respectively. These exceeded acute exposure estimates. There was limited evidence of risk modification based on prematurity or cardiopulmonary disease. A review of the potential biases, strengths, and limitations in these data and study designs suggests that exposure classification was most valid for PM and the protective effects of ozone were likely a manifestation of its negative correlation with PM2.5. Potential systematic downward bias in the case-crossover derived risk estimates was explored. In summary, these novel data support a link between elevations in PM2.5 and the risk of infant bronchiolitis hospitalization. Efforts to evaluate this in different populations with more refined exposure measurement are merited.


Journal Articles on this Report : 7 Displayed | Download in RIS Format

Other subproject views: All 21 publications 14 publications in selected types All 14 journal articles
Other center views: All 209 publications 113 publications in selected types All 109 journal articles
Type Citation Sub Project Document Sources
Journal Article Karr C, Lumley T, Shepherd K, Davis R, Larson T, Ritz B, Kaufman J. A case crossover study of wintertime ambient air pollution and infant bronchiolitis. Environmental Health Perspectives 2006;114(2):277-281. R827355 (Final)
R827355C001 (Final)
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  • Abstract from PubMed
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  • Journal Article Liu L-JS, Slaughter JC, Larson TV. Comparison of light scattering devices and impactors for particulate measurements in indoor, outdoor, and personal environments. Environmental Science & Technology 2002;36(13):2977-2986. R827355 (2004)
    R827355 (Final)
    R827355C001 (Final)
    R827355C003 (2001)
    R827355C003 (2002)
    R827355C003 (Final)
    R827355C008 (Final)
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  • Journal Article Miller KA, Siscovick DS, Sheppard L, Shepherd K, Sullivan JH, Anderson GL, Kaufman JD. Long-term exposure to air pollution and incidence of cardiovascular events in women. New England Journal of Medicine 2007;356(5):447-458. R827355 (Final)
    R827355C001 (Final)
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  • Journal Article Sheppard L, Lumley T. Comment in: Dominici F, Samet JM, Zeger SL. Combining evidence on air pollution and daily mortality from the 20 largest U.S. cities: a hierarchical modelling strategy. Journal of the Royal Statistical Society Series A-Statistics in Society 2000;163(3):297. R827355 (2001)
    R827355 (Final)
    R827355C001 (Final)
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  • Journal Article Sullivan JH, Schreuder AB, Trenga CA, Liu SL, Larson TV, Koenig JQ, Kaufman JD. Association between short term exposure to fine particulate matter and heart rate variability in older subjects with and without heart disease. Thorax 2005;60(6):462-466. R827355 (Final)
    R827355C001 (Final)
    R827355C009 (2003)
    R827355C009 (Final)
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  • Journal Article Sullivan JH, Hubbard R, Liu SL-J, Shepherd K, Trenga CA, Koenig JQ, Chandler WL, Kaufman JD. A community study of the effect of particulate matter on blood measures of inflammation and thrombosis in an elderly population. Environmental Health 2007;6:3 (7 pp.). R827355 (Final)
    R827355C001 (Final)
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  • Journal Article Sullivan J, Sheppard L, Schreuder A, Ishikawa N, Siscovick D, Kaufman J. Relation between short-term fine-particulate matter exposure and onset of myocardial infarction. Epidemiology 2005;16(1):41-48. R827355 (Final)
    R827355C001 (2003)
    R827355C001 (Final)
    R827355C009 (2003)
    R827355C009 (Final)
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  • Supplemental Keywords:

    ambient particles, fine particles, combustion, health, exposure, biostatistics, susceptibility, human susceptibility, sensitive populations, air toxics, genetic susceptibility, indoor air, indoor air quality, indoor environment, tropospheric ozone, California, CA, polyaromatic hydrocarbons, PAHs, hydrocarbons, acute cardiovascular effects, aerosols, air pollutants, air pollution, air quality, airborne pollutants, airway disease, airway inflammation, allergen, ambient aerosol, ambient aerosol particles, ambient air, ambient air quality, ambient particle health effects, animal model, assessment of exposure, asthma, atmospheric aerosols, atmospheric chemistry, biological markers, biological response, cardiopulmonary response, cardiovascular disease, children, children’s vulnerability, combustion, combustion contaminants, combustion emissions, epidemiology, exposure, exposure and effects, exposure assessment, harmful environmental agents, hazardous air pollutants, health effects, health risks, human exposure, human health effects, human health risk, incineration, inhalation, lead, morbidity, mortality, mortality studies, particle exposure, particle transport, particulates, particulate matter, PM, risk assessment,, RFA, Health, Scientific Discipline, PHYSICAL ASPECTS, Air, Geographic Area, particulate matter, Toxicology, air toxics, Environmental Chemistry, Health Risk Assessment, Epidemiology, State, Northwest, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, Allergens/Asthma, Biochemistry, Physical Processes, Children's Health, genetic susceptability, indoor air, Atmospheric Sciences, Incineration/Combustion, ambient aerosol, ambient air quality, asthma, biostatistics, health effects, particulates, risk assessment, sensitive populations, air pollutants, cardiopulmonary responses, health risks, human health effects, morbidity, exposure and effects, acute cardiovascular effects, airway disease, ambient air, exposure, hazardous air pollutants, animal model, epidemelogy, combustion emissions, biological response, air pollution, children, Human Health Risk Assessment, airway inflammation, particle exposure, airborne pollutants, cardiopulmonary response, human exposure, inhalation, PAHs, atmospheric aerosols, children's vulnerablity, assessment of exposure, ambient particle health effects, mortality studies, combustion, harmful environmental agents, hydrocarbons, epidemeology, human susceptibility, biological markers, incineration, indoor air quality, mortality, California (CA), allergens, aerosols, air quality, allergen, atmospheric chemistry, cardiovascular disease, combustion contaminants, exposure assessment, human health risk, indoor environment, particle transport, toxics

    Relevant Websites:

    http://depts.washington.edu/pmcenter/ Exit

    Progress and Final Reports:

    Original Abstract
  • 1999 Progress Report
  • 2000 Progress Report
  • 2001 Progress Report
  • 2002 Progress Report
  • 2003 Progress Report
  • 2004

  • Main Center Abstract and Reports:

    R827355    Airborne PM - Northwest Research Center for Particulate Air Pollution and Health

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R827355C001 Epidemiologic Study of Particulate Matter and Cardiopulmonary Mortality
    R827355C002 Health Effects
    R827355C003 Personal PM Exposure Assessment
    R827355C004 Characterization of Fine Particulate Matter
    R827355C005 Mechanisms of Toxicity of Particulate Matter Using Transgenic Mouse Strains
    R827355C006 Toxicology Project -- Controlled Exposure Facility
    R827355C007 Health Effects Research Core
    R827355C008 Exposure Core
    R827355C009 Statistics and Data Core
    R827355C010 Biomarker Core
    R827355C011 Oxidation Stress Makers