&EPA
THE
ESA
AIR POLLUTION STUDY
Strengthening the
Scientific Foundation for Air
Quality Management
www.epa.gov/ncer
While it is widely known that
factors such as cigarette smoking
and high blood pressure are
linked to cardiovascular disease,
studies indicate that long-term
exposure to air pollution also is
associated with premature death
from this disease.
IN 2004, THE ENVIRONMENTAL PROTECTION AGENCY (EPA)
awarded a grant to the University of Washington for the Multi-Ethnic
Study of Atherosclerosis (MESA) Air Pollution Studyan unprec-
edented investigation of the impact of air pollution on hardening
of the arteries, or atherosclerosis. This long-term study investigates
key questions about the possible effects of fine particles in
air pollution on the development of heart disease and mortality.
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THE MESA AIR POLLUTION STUDY
Air Pollution and Cardiovascular Health
missions from power plants, traffic, wood
- burning, and other combustion processes form
airborne particles and liquid droplets of chemi-
cals. While inhaled particulate matter (PM) ranges
in size from particles tens of micrometers in diameter
(PM10) to minute particles less than 0.1 micrometer in
diameter, combustion sources generate fine particles
less than 2.5 micrometers in diameter (PM2.5), just
1/30 the width of a human hair.
Two landmark studies, originally published in the 1990s with later follow-
up reports, indicated that these fine particles pose the greatest mortality risk
from air pollution.1"4 In 1999 and 2006, EPA revised the National Ambient
Air Quality Standards for particulate matter to address PM2 5 concentrations.
Since 1999, EPA also has supported a national PM2 5 monitoring network,
managed by federal, state and local governments.
Although scientific evidence is accumulating that supports the link between
PM exposure and premature mortality and adverse health events, many ques-
tions about the health effects of PM remain unanswered. In 2001, the National
Research Council highlighted a critical need for further research on the long-
term health effects of PM exposure, particularly in two areas: the effects of PM
in combination with gaseous pollutants (such as nitrogen dioxide and ozone),
and the effects on potentially susceptible groups. The MESA Air Pollution
Study addresses these and other research needs.
BUILDING KNOWLEDGE
OF PM HEALTH EFFECTS
In accordance with its mission to protect human health,
the ultimate goal of EPAs PM research program is to
provide information for decision-making. EPA conducts
and funds research designed to answer key questions
concerning pollution emissions, exposure, health effects
and air quality management.
EPA's Science to Achieve Results (STAR)
research program, through its competitive grants
process, has funded several epidemiological studies
investigating long-term exposure to PM2 5 in
addition to the MESA Air Pollution Study. STAR
support of the study will substantially add to this
body of research.
IMPROVING OUR KNOWLEDGE BASE
The MESA Air Pollution Study investigates the impact
of air pollution on the progression of cardiovascular
disease among more than 7000 participants with diverse
backgrounds from nine locations in six states for 10
years. The central scientific hypothesis for this study is
that long-term exposure to fine particles is associated
with a more rapid progression of coronary atheroscle-
rosis and an increased risk of coronary events.
To test this hypothesis, a host of air pollution and
participant health measures are being collected and
analyzed. Along with measuring PM concentrations
and variability at the neighborhood, home and indi-
vidual levels, the MESA Air Pollution Study is using
data from the national PM2 5 monitoring system. These
environmental data will be integrated into a model to
estimate long-term PM exposure for all study partici-
pants. The cardiovascular health of each participant
also will be tracked, with a subgroup of 3600 partici-
pating in additional medical evaluations for subclin-
ical, asymptomatic progression of atherosclerosis.
The MESA Air Pollution Study will address
the following critical scientific questions concerning
PM-related health effects:
1. What role does long-term particle
exposure play in the progression of coro-
nary artery disease and the onset of clinical
cardiovascular disease, including heart
failure, heart attacks and mortality?
2. Are some ethnic populations more suscep-
tible to the effects of particle exposure?
3. Does the presence of gaseous pollutants
change the health risks associated with
ambient particulate matter?
COLLABORATING WITH PREEMINENT
RESEARCHERS: THE MESA STUDY
The MESA Air Pollution Study is built on the frame-
work of the Multi-Ethnic Study of Atherosclerosis
(MESA) which is a 10-year, large-scale epidemiological
study of cardiovascular risk factors and atherosclerosis
initiated in 1999 by the National Heart, Lung, and
Blood Institute (NHLBI) of the National Institutes of
Health. NHLBI-MESA recruited at baseline approxi-
mately 1100 participants aged 45-84 years in each of six
major metropolitan areasLos Angeles, CA, St. Paul,
MN, Chicago, IL, New York City, NY, Baltimore, MD,
and Winston-Salem, NC. MESA researchers continue
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www.epa.gov/ncer
RESEARCH COLLABORATION
ENCOURAGED
The investigators of the MESA Air Pollution Study
invite proposals from other investigators to explore
additional research questions. Researchers can gain
access to monitoring data or physiological data and
samples from both the NHLBI-MESA and MESA Air
Pollution Studies. The proposed research must secure
independent funding. Further information about
research opportunities and the process for proposing
collaborative projects can be obtained at the MESA
Air Pollution Study Web site or by contacting the
principal investigator, Dr. Joel Kaufman. (Please see
contact information on the back page.)
BEHIND THE MESA AIR POLLUTION STUDY
The Multi-Ethnic Study of Atherosclerosis (MESA)
the NHLBI epidemiological studyis the foundation
of the MESA Air Pollution Study. The collaborating
institutions in the NHLBI-MESA also are partici-
pating in the MESA Air Pollution Study. These
collaborators include the University of California-
Los Angeles, Columbia University, Northwestern
University, University of Minnesota, Johns Hopkins
University, Wake Forest University, University of
Vermont, and Tufts-New England Medical Center.
The University of Southern California and University
of Michigan are also collaborators.
The MESA Air Pollution Study is based at
the University of Washington Department of
Environmental and Occupational Health Sciences.
The study's Principal Investigator is Dr. Joel
Kaufman. The study's exposure assessment efforts
are directed by Dr. Martin Cohen.
EXPECTED OUTCOMES
The MESA Air Pollution Study will provide:
More precise estimates of the risks for the progression of
underlying coronary artery disease and mortality associated
with long-term exposure to ambient PM2 5.
More information on the role played by traffic-related air
pollution and regional air pollution.
Identification of groups especially susceptible to the effects
of PM25 exposure due to racial/ethnic background, poor
health status, older age, and other characteristics.
A better understanding of the health risks posed by exposure
to gaseous pollutants concurrently with particulate matter.
Opportunities for research collaboration.
MESA Air Pollution Study: In Brief
STUDY POPULATION
More than 7000
participants
recruited from
the NHLBI-MESA
Study, the NHLBI-
MESA Family
Study, and addi-
tional participants
in New York and
southern California
STUDY SITES
(Nine Locations)
Six field sites established
by the NHLBI-MESA
Study in Chicago, Los
Angeles County, Baltimore,
St. Paul, New York City,
and Winston-Salem
An additional area near
New York City and two
additional areas in and
around Los Angeles
The MESA Air Pollution Study will help determine
if cardiac disease is accelerated by exposure
to PM in combination with gaseous pollutants.
STUDY APPROACH
HEALTH ASSESSMENTS:
All participants tracked for clinical cardiovascular
events (heart attack, heart failure, death, etc.)
A subgroup of 3600 receive two clinical examinations
five years apart to be assessed for pre-symptomatic
progression of atherosclerosis
PM EXPOSURE ASSESSMENTS:
Air pollution data collected from existing networks,
study-specific outdoor monitors, roughly 330
monitors in homes, and personal monitors (carried
by approximately 80 participants)
PM2 5 exposure model developed, based on air
monitoring and questionnaire data
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Strengthening the Scientific Foundation for Air Quality Management
MESA AIR POLLUTION STUDY
FIELD CENTERS
SOURCE: MESA AIR
POLLUTION DATABASE
AUTHOR: MICHALIS AVRAAM
2006
The study follows
a diverse group of
men and women from
communities distrib-
uted throughout six
metropolitan areas.
to conduct medical evaluations, including collecting
detailed health data from participants who will receive
a total of four clinical examinations by 2007.
Several academic institutions have secured grant
funding to address additional scientific questions
in the NHLBI-MESA study population, including
measurements of lung function (MESA Lung Study)
and genetic markers of susceptibility to disease
(MESA Family Study). The University of Washington
designed the MESA Air Pollution Study in part-
nership with the NHLBI-MESA researchers. The
investigation of the role of PM in cardiovascular
health relies on and adds to the NHLBI-MESA effort.
The MESA Air Pollution Study is recruiting several
hundred additional study participants and will repeat
clinic health assessments in 2010 for the subgroup
of 3600 participants undergoing further assessment
for asymptomatic evidence of atherosclerosis. The
supplemental data collection will contribute to the
value of the broader NHLBI-MESA goals.
USING SOPHISTICATED
EXPOSURE ASSESSMENTS
The MESA Air Pollution Study team will combine
air quality data collected by government agencies
with the study's own monitoring effort to develop an
exposure model. This model will combine air quality
data, meteorological data, traffic information, land
Answering Critical Questions
THE PROGRESSION AND
ONSET OF HEART DISEASE
In determining associations with PM
exposure, the MESA Air Pollution
Study is assessing heart disease at
three levels:
The occurrence of cardio-
vascular events, such as
heart failure, heart attack,
stroke, angina, and medical
interventions;
Changes in asymptomatic
cardiovascular disease; and,
Early indicators of biological
stress.
At the study's inception, partici-
pants were free of clinically-recog-
nized (or symptomatic) cardiovascular
disease. For the duration of the
study, they are being followed for
the occurrence of cardiovascular
events and cardiovascular death.
All participants provided data on
individual characteristics, activi-
ties and behaviors, medical history
and current use of medications, diet
and dietary supplements, and social
determinants of health. Every year
the study participants are contacted
to report medical diagnoses made
by a physician, significant medical
procedures, and to identify deaths
that may have occurred. All reports of
cardiovascular diagnosis and death
are verified by study physicians using
hospital medical records and death
certificates.
A subgroup of 3600 participants
is undergoing additional clinical
assessment for the progression of
cardiovascular disease in its early,
symptom-free stages. To identify
underlying heart disease, investiga-
tors are using the following advanced
noninvasive medical techniques:
Computed tomography (CT)
scans to determine the pres-
Noninvasive tests will enable researchers to
compare the progression of early, symptom-free
heart disease with levels of PM exposure.
ence of coronary artery calci-
fication, a reliable indicator of
atherosclerosis.
Ultrasounds to assess the
thickness of the arterial wall at
specific points on the carotid
artery (in the neck). This
measurement, referred to as
intima-media thickness (IMT), is
used to determine the extent of
atherosclerosis and the risk of
heart attacks and strokes.
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MESA Air Pollution Study researchers are conducting air monitoring
at each study location to understand the variation in concentrations
of selected pollutants within the communities where participants
reside. The monitors on the lamppost in the first photo are two
of more than 100 sited periodically throughout each study area
measuring NO2 and NOX. These monitors are used to determine the
spatial variability of air pollution levels and the contribution from
vehicular traffic. The monitor in the second photo will remain in place
for the duration of the study and is measuring trends over time in
PM25, NO2 and NOX as well as the impact of nearby traffic.
use and other geographic data, and individual time
activity data to estimate the exposure levels of each
study participant.
Recognizing that air pollution varies within metro-
politan areas, investigators are characterizing exposure
down to the neighborhood level. To supplement the
fixed air quality monitors maintained by government
agencies, study personnel have conducted monitoring
in the communities and outside of about 100 homes in
each study area. Within 18 months of joining the study,
participants have had PM2 5 and gaseous pollutants
measured two times for two-week periods using neigh-
borhood monitors. To determine how much outdoor
air pollution contributes to indoor PM exposure, some
participants' homes have been equipped with indoor
monitors for these same two-week periods. Lastly, to
get a more precise estimate of individual exposure and
to verify the assumptions used in the project's expo-
sure model, some participants from these households
are wearing personal monitors.
Outdoor monitors also will be used to identify
relationships between PM concentrations and factors
such as distance to major roads and other PM sources.
These relationships will be incorporated into the
exposure model in order to estimate exposure concen-
trations at each participant's residential address.
The University of Washington has leveraged this
monitoring effort with the support of the Health
Effects Institute to study the role of PM components
on health effects associations.
To gain insight on how PM
could induce atherosclerosis and
heart disease, investigators also
are assessing a subgroup of 720
subjects for plasma (blood) markers
of inflammation, oxidative damage,
and impaired blood vessel func-
tion. Research has shown that these
biological markers may play a role
in the development and progression
of atherosclerotic plaques in the
blood vessel wall.
DIFFERENCES IN
SUSCEPTIBILITY
The risk of coronary artery disease
has been shown to vary by race
and ethnicity. NHLBI-MESA and the
MESA Air Pollution Study are
following a diverse group of older
men and women between ages 50-89.
Investigators will consider whether
individual characteristics, such as age,
the presence of subclinical disease
White
African-
American
Hispanic
Asian
or risk factors for diseases, residen-
tial location (inner-city or suburban),
education level, and race or ethnicity,
increase susceptibility to the adverse
health effects of long-term exposure
to ambient PM. They also will consider
the influences of factors that result
in a higher exposure burden, such
as physical activity levels, differences
in outdoor activities, residential prox-
imity to pollution sources, housing
characteristics, air conditioner
use, and exposure to indoor particle
sources, such as wood-burning
stoves and cigarette smoke.
RACE/ETHNICITY
OF STUDY PARTICIPANTS
The MESA Air Pollution Study population
is comprised of the following races and
ethnicities: 38% white, 28% African-American,
22% Hispanic, and 12% Asian (predominately
of Chinese descent).
PM AND GASEOUS
POLLUTANTS
Depending on geographic location
and season, ambient PM levels can
be associated with certain gaseous
co-pollutants. Health responses
might be stimulated by a mixture
of PM components or by the simul-
taneous or sequential exposure to
gaseous pollutants, such as ozone,
in ambient air. The comprehensive
monitoring and modeling being done
in the MESA Air Pollution Study will
help researchers and policymakers
better understand health effects
from PM in combination with other
ambient pollutants.
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&EPA
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REFERENCES
1 The Harvard Six-Cities Study:
Dockery, D.W., Pope, C.A. Ill, Xu, X., et
al. (1993). An association between air
pollution and mortality in six U.S. cities.
N EnglJ Med 329:1753-59.
2 Follow-up of the Harvard Six Cities
Study: Laden, R, Schwartz, J., Speizer,
F.E., Dockery, D.W. (2006). Reduction
in fine particulate air pollution and
mortality: extended. Am J Respir Crit
Care Med 173:667-72.
3 American Cancer Society studies:
Pope, C.A. Ill, Thun, M., Namboodiri, M.,
et al. (1995). Particulate air pollution as
a predictor of mortality in a prospective
study of U.S. adults. Am J Respir Crit
Care Med 151:669-74.
4 Pope, C.A. Ill, Burnett, R.T.,
Thurston, G.D., Thun, M.J., Calle, E.E.,
Krewski, D., Godleski, J.J. (2004).
Cardiovascular mortality and long-term
exposure to particulate air pollution:
epidemiological evidence of general
pathophysiological pathways of disease.
Circulation. 109(1):71-7.
WEB RESOURCES
The MESA Air Pollution Study
www.mesaairpollution.org | This site provides study information, background,
and contacts.
EPA National Center for Environmental Research (NCER)
www.epa.gov/ncer | This site describes EPA's extramural research program for
exposure, effects, risk assessment, and risk management. NCER supports the
STAR (Science to Achieve Results) grants program and graduate and undergraduate
fellowships programs. Details regarding the MESA Air Pollution Study can by found
by conducting a search for grant number R831697 at www.epa.gov/ncer/grants.
EPA Particulate Matter and Air Pollution
www.epa.gov/air/particlepollution | EPA provides information on PM, including
general description, health effects, environmental effects, regulatory actions, moni-
toring, and links to research.
AIRNow
www.airnow.gov | This cross-agency Web site provides the daily Air Quality Index
with maps and information on day-to-day air quality in the United States.
EPA Particulate Matter Research
www.epa.gov/pmresearch | These pages describe the research being done by
EPA to better understand particle emissions, transport and atmospheric chemistry,
and particle exposure and associated health effects.
DISCLAIMER: The research described in this document has been funded partially by the
U.S. Environmental Protection Agency under the STAR Program. The information does not
necessarily reflect the views of the Agency, and no official endorsement should be inferred.
.
an
Office of Research
and Development
Washington DC 20460
EPA/600/S-06/003
December 2006
CONTACTS FOR THE MESA AIR POLLUTION STUDY
Joel Kaufman, M.D., M.P.H.
Principal Investigator
Dept. of Environmental and
Occupational Health Sciences
School of Public Health
and Community Medicine
University of Washington
Box 354695
Seattle, Washington 98105-4695
(206) 897-1723
mesaair@u.washington.edu
Barbara Glenn, Ph.D.
Physical Scientist
U.S. Environmental Protection Agency
Office of Research Development
National Center
for Environmental Research
8723F
1200 Pennsylvania Avenue, N.W.
Washington, D.C. 20460
(202) 343-9721
glenn.barbara@epa.gov
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