2006 Progress Report: Relating Cardiovascular Disease Risk to Ambient Air Pollutants Using Geographic Information Systems Technology and Bayesian Neural Networks: The AHSMOG Study

EPA Grant Number: R830547
Title: Relating Cardiovascular Disease Risk to Ambient Air Pollutants Using Geographic Information Systems Technology and Bayesian Neural Networks: The AHSMOG Study
Investigators: Knutsen, Synnove F. , Beeson, Larry , Ghamsary, Mark , Soret, Samuel
Institution: Loma Linda University
EPA Project Officer: Chung, Serena
Project Period: February 1, 2003 through December 31, 2006 (Extended to January 31, 2009)
Project Period Covered by this Report: February 1, 2006 through January 31,2007
Project Amount: $964,436
RFA: Epidemiologic Research on Health Effects of Long-Term Exposure to Ambient Particulate Matter and Other Air Pollutants (2002) RFA Text |  Recipients Lists
Research Category: Health Effects , Particulate Matter , Air

Objective:

The primary objective of this project is to determine the association between cardiovascular disease and long term particulate ambient pollutants in 6,338 non-smoking California Seventh-day Adventists. The outcomes include both fatal and non-fatal coronary heart disease as well as other cardiovascular disease during 22 years of follow-up. Further, the objectives are to assess the same effects in sensitive subgroups (e.g., prevalent CVD, hypertensives, diabetics, elderly).

Further, this study aims to assess whether other pollutants (specifically gaseous pollutants) modify the association between particulate pollution and CVD.

Approach:

  1. Utilize data from the existing AHSMOG Study, which has been updated through March 2000 through the current EPA STAR Grant (R-82799801-0). This data includes monthly indices of air pollutants to zip code centroids, monthly residence and work location histories, outcome assessment (CHD, fatal and non-fatal) and assessment of relevant confounders (smoking, environmental tobacco smoke, diet, exercise, etc).
  2. Develop new indices of ambient air pollutants for the individual subjects in the AHSMOG Study using Geographic Information Systems (GIS) technology and stochastic models that include error estimates of the indices.
  3. Develop non-linear statistical models using Bayesian neural networks to develop alternative analytical strategies for modeling the relationship between different ambient air pollutants and risk of CHD where several pollutants and latent (unobserved) and missing values can be incorporated.
  4. Compare new methods developed under approaches 2 and 3 to the classic or conventional methods previously used in the AHSMOG Study.

Progress Summary:

Air Pollution Estimates

The AHSMOG study already had monthly air pollution estimates for each subject since start of study in 1973 and for some pollutants (PM2.5) back to 1966. These were developed using a deterministic method with interpolation to the centroid of each zipcode. The AHSMOG study had used information from all relevant monitoring stations in California to develop their ambient air pollution estimates. However, in meetings between the STAR grantees and EPA, it was decided to use a common air pollution database from EPA. This will allow a comparison of estimated ambient air pollution values by the four studies. For AHSMOG, this will also allow a comparison with our previous, comprehensive methods for estimation of ambient air pollution. However, this decision has also delayed the progress of the study in obtaining air pollution estimates using geostatistical methods.

To date, we have developed individual mean estimates of the different air pollutants for 1977 to 1999 (or date of death) based on monthly residence history and monthly workplace zipcode which have been geocoded. In collaboration with the research team at Environmental Systems Research Institute (ESRI) we have developed a software program that can combine the geocoded residence and workplace information with the EPA air pollution database to assess subject-specific ambient air pollution estimates using geostatistical data analysis. Thus we have subject-specific ambient air pollutant values for the entire AHSMOG cohort.

In addition, we have done analyses for risk assessment of fatal CHD and total mortality using alternate statistical methods including Bayesian Neural Networks and Bayesian Cox (using BUGS software program).

Assessment of outcome

Incident CHD
From 1977-1982, we have information on and verification of incident myocardial infarctions (MI). For the period 1983-1999 we have self-reported incidence of acute myocardial infarction with additional information on name and address of the hospital in which these were diagnosed. Validity of this information was planned through obtainment of medical records from the individual hospitals. However, this has proved impossible as hospitals do not keep medical records usually for more than 5 years in-house. After that they are put in remote storage and if records are older than 10 years, they are often destroyed. Thus, we have not been able to obtain more than 56% of the records or a total of 318 of 568.

To compensate for a lack of data for incident CHD, we requested permission from EPA to modify this part of the study and instead assess incident CHD in a new cohort, the Adventist Health Study 2 (AHS-2) cohort. This cohort of 100,000 subjects has recently been assembled through funding from NCI to study the effect of lifestyle, especially diet, on cancer outcomes. We propose to use the information from bi-annual hospitalization forms to study the association between particulate air pollution and incident CHD using this new cohort. This will be a separate stand-alone study and we are currently pursuing funding possibilities.

Mortality

All death certificates have been coded by a certified nosologist and all mortality outcomes have thus been updated. A total of 2,462 deaths have occurred in the cohort since 1977. Of these, 2,393 are natural cause deaths (ICD-9 < 800) and 644 are due to ischemic heart disease (ICD-9: 410-414).

Analyses and Results:

Coronary Heart Disease mortality

A paper has been published (Environ Health Perspect 2005;113:1723-9) assessing the effect of fine particles on the risk of CHD in males and females and finding a stronger effect in females than in males. This surprising finding of a strong effect in females has since been replicated by others using data from the larger cohort of the WHI study (Miller et al. N Engl J Med, 2007;356(5):447-58).

We are currently, with the help of a graduate student, assessing whether our observed gender difference could be due to a greater degree of misclassification of exposure among males.

Outcomes in sensitive subgroups –

The following sensitive subgroups have been identified:

  • Older age (>64 yrs and > 74 yrs)
  • Prevalent CHD of stroke
  • Prevalent diabetes
  • Past smokers
  • Prevalent chronic obstructive pulmonary disease (COPD)

Preliminary analyses of sensitive subgroups using previously estimated ambient air pollution do not indicate any increased risk associated with PM10 in sensitive subgroups, except for persons with diabetes where the risk of ANC, cardiopulmonary and CHD mortality seems to be elevated among males. A draft manuscript is available.

We have limited numbers to assess the health effects of fine PM except for possibly all natural cause mortality.

Outcomes in the full AHSMOG study

Cancer
With regards to total cancer mortality, we find, as in an earlier report, an elevated risk of total cancer among females also in the 22 year follow-up. These data will presented at ISEA, 2007.

For individual cancers, we find, in two-pollutant models with ozone, elevated risk of both lung cancer and non-Hodkin Lymphoma associated with particulate matter (PM10).

Total mortality outcomes
Our findings are in broad agreement with other studies. In two-pollutant models with ozone, we find 5% increased, although not statistically significant, risk of ANC associated with a 10 μg/m3 mean incremental increase in PM10 for both genders. For cardiopulmonary and CHD mortality as well as non-malignant respiratory mortality, we find that the effect is somewhat stronger in females than in males. A poster was presented at ISEE, 2007 on the non-malignant respiratory mortality.

Progress

To date, one paper has been published, two papers have been submitted, 8 presentations have been given at scientific meetings. An additional 2 papers are available in draft form and 10 other papers are being worked on, some with the help of graduate students. See under “Future activities”, below, for more details on publications/presentations.

As mentioned earlier, the aim of assessing the relationship between ambient air pollution and incident CHD cannot be fulfilled and we are pursuing fresh funding to be able to assess this in a newly established NCI funded cohort of 100,000 Adventists, the Adventist Health Study 2 (AHS-2).

The development of GIS based individual ambient air pollution estimates has been completed for PM10, PM2.5, NO2, SO2 and ozone. We have worked in close collaboration with ESRI and have developed an automated program that can estimate individual and time specific measures based on GIS krieging of the air pollutant and the subject’s residence and work location. We are currently cross-validating air pollution estimates using GIS based krieging versus a deterministic model and assessing potential bias introduced in our models using spatial interpolation methods.

Likewise, the development of statistical models using neural networks and Bayesian neural networks is now completed. We have also been able to use the BUGS statistical software to do Bayesian Cox analyses. Dr. Ghamsary has worked closely with the developers of this software in order to make it run with large datasets such as ours. Comparing the risk estimates using BUGS with estimates using traditional COX analysis, was reassuring as they gave virtually the same estimates. This work has been submitted for publication.

Due to small number of cancer mortality cases on certain endpoints, we are currently evaluating whether to do a new linkage with NDI to extend our follow-up by 7 years and thus get more cases.

A paper on total cancer and PM will be presented at ISEA, 2007.

The results of the association between PM10 and non-malignant respiratory mortality was presented at ISEE, 2007.

Expenditures to date

As of February 28, 2007, the grant had spent $ 791,819.41. We have asked for a non-cost extension to complete the publication of the remaining manuscripts.

Future Activities:

We are definitely into our publication phase and are currently working on the following papers:

  1. Shavlik D et al. Evaluation of spatial interpolation methods on PM10 and assessing and adjusting for bias in RRs using spatial interpolation methods.
  2. Shavlik D et al. Adjusting AHSMOG data for spatial auto correlation using generalized mixed models.
  3. Beeson WL et al. Risk of hospitalizations for CHD and respiratory disease as associated with ambient air pollution.
  4. Ghamsary M et al. The risk of fatal CHD and daily travel on freeways/highways and distance from residence to freeways.
  5. Knutsen SF, Shavlik D et al. The effect of ambient air pollution on risk of fatal and non-fatal respiratory cancer.
  6. Knutsen SF, Chen LH et al. PM2.5 and risk of cancer. Are women at higher risk?
  7. Knutsen SF, Chen LH et al. Ambient air pollution and mortality among diabetics.
  8. Soret S et al. Cross-validation of ozone exposure estimates for alternative spatial resolutions of subjects in air pollution studies.
  9. Soret S et al. Zipcode or residence based individual ambient air pollution estimates – does it affect risk estimates for disease?
  10. Metgalchi S, Beeson WL, Knutsen SF. The association between particulate matter and emphysema and asthma. Results from 22 years follow-up in the AHSMOG study.


Journal Articles on this Report : 1 Displayed | Download in RIS Format

Other project views: All 25 publications 4 publications in selected types All 4 journal articles
Type Citation Project Document Sources
Journal Article Chen LH, Knutsen SF, Shavlik D, Beeson WL, Petersen F, Ghamsary M, Abbey D. The association between fatal coronary heart disease and ambient particulate air pollution:are females at greater risk? Environmental Health Perspectives 2005;113(12):1723-1729. R830547 (2005)
R830547 (2006)
R830547 (2007)
R830547 (Final)
R827998 (Final)
  • Full-text from PubMed
  • Abstract from PubMed
  • Associated PubMed link
  • Full-text: EHP-Full Text HTML
  • Other: EHP-Full Text PDF
  • Supplemental Keywords:

    Ambient air, ozone, particulate matter, exposure, risk, risk assessment, health effects, human health, sensitive populations, population, elderly, cumulative effects, susceptibility, epidemiology, modeling, monitoring, analytical, Bayesian neural networks, GIS, southwest, California, CA,, RFA, Economic, Social, & Behavioral Science Research Program, Health, Scientific Discipline, Air, ENVIRONMENTAL MANAGEMENT, particulate matter, Health Risk Assessment, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, Disease & Cumulative Effects, Biochemistry, Environmental Statistics, genetic susceptability, Biology, Risk Assessment, ambient air quality, elderly adults, health effects, sensitive populations, health risk analysis, air pollutants, long term exposure, acute lung injury, Bayesian approach, cardiovascular vulnerability, Bayesian neural networks, Bayesian method, exposure, air pollution, chronic health effects, particulate exposure, susceptibility, statistical models, human exposure, sensitive subjects, Acute health effects, elderly, GIS, sensitive subgroups, mortality, cardiotoxicity, tobacco smoke, age dependent response, cumulative effects, cardiopulmonery responses, respiratory, exposure assessment, environmental hazard exposures, toxics, human health risk, cardiovascular disease

    Relevant Websites:

    http://www.llu.edu/llu/health/ahsmog.htm Exit

    Progress and Final Reports:

    Original Abstract
  • 2003 Progress Report
  • 2004 Progress Report
  • 2005 Progress Report
  • 2007 Progress Report
  • Final Report