Report of the Working Group
Determining the Role of Subclinical Disease Testing
in Patients at Intermediate Risk
TABLE OF CONTENTS
Background
The objective of the Working Group was to provide advice to the
National Heart, Lung, and Blood Institute about research that
is currently needed to inform clinical guidelines for the use
of subclinical cardiovascular disease testing to identify persons
at high risk for CVD and to target intervention. The group met
in Bethesda for a day and a half, July 13-14, 2004, followed by
a one-hour conference call on July 23 among a subset of members
and NHLBI staff. A list of the Working Group
members is at the end of this report.
A major focus of cardiovascular epidemiology research has been the identification of risk factors,
singly or in combination, that enhance the ability to predict clinical cardiovascular disease events.
Such research has provided insights into the pathophysiology of the development of cardiovascular
disease and, in the case of the “traditional” risk factors, into direct avenues for prevention through
interventions targeted at factors such as smoking, high blood pressure, and high cholesterol.
In recent years, a variety of other measures, ranging from serum and urinary markers to direct vascular
imaging, have been documented to predict cardiovascular disease events independent of traditional risk
factors, although the magnitude of the additional prediction is generally modest. Several of these
measures, most recently C-reactive protein and coronary calcium imaging, appear to be becoming
become widespread clinical tools. The projections for cardiovascular disease care forecast dramatic
increases in utilization and expenditures in the near future. At the same time, there is
widespread confusion among clinicians regarding when to use such tests and what the appropriate
response to test results is. Much of the testing is performed outside of the clinical setting
through direct to consumer marketing. The fact that the health consequences and downstream costs
of testing and treatment strategies are not known was deemed a major consideration by the Working
Group.
The meeting began with an overview of the recommendations that
have addressed this issue offered since 2000 by the American Heart
Association, the American College of Cardiology, and the US Preventive
Health Services Task Force. Several groups have suggested that
the group in which testing is most likely to be useful in making
treatment decisions is that at “intermediate” risk, based on the
Framingham risk score – that is, a 10-year risk for coronary heart
disease of 6-20%. Data regarding the distributions of these measures
in persons at intermediate risk were presented. The possible research
questions and designs for a clinical trial were discussed. Information
about possible measures, particularly the strength of their associations
with cardiovascular disease and how well each met criteria as
possible screening tools, was presented. Possible clinical algorithms
for screening and treatment, issues regarding the population to
be included in a clinical trial, types of outcomes to be measured,
and the types of treatments that might be offered to high risk
individuals were discussed. Finally, alternate designs for a clinical
trial were debated.
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Review of Previous Recommendations
Drs. Greenland and Taylor noted that approximately 650,000 persons in the United States have first
coronary heart disease events annually, and that 25% of all coronary heart disease patients present with
sudden death. Numerous studies have documented the effectiveness of targeting and treating high risk
patients. However, a large proportion of cases arise from persons at intermediate risk. The question
now is whether risk prediction can be refined and treatment targeted more effectively among those at
intermediate risk. One challenge is to identify tests that are powerful enough to discriminate –
particularly beyond our current ability to discriminate – between persons who will and will not develop
CVD.
Drs. Greenland and Taylor reviewed existing guidelines for risk reduction of CHD aimed at those at
high and intermediate risk, including the following:
- American Heart Association Statement on Electron Beam Computed
Tomography (2000)
- AHA Prevention V Conference (2000)
- National Cholesterol Education Program (2001)
- Joint National Committee on the Detection, Evaluation, and
Treatment of High Blood Pressure (2001)
- Addendum to AHA Prevention V conference (2001)
- American College of Cardiology Bethesda Conference #33 (2002)
- American College of Cardiology Bethesda Conference #34 (2003)
- AHA/CDC Statement on CRP (2003)
- US Preventive Health Services Task Force Clinical Guidelines
on Screening for Coronary Heart Disease (2004)
It was also noted that Blue Cross/Blue Shield issued a medical policy in 2000 that did not recommend
use of coronary calcium imaging. A group promoting the concept of the “vulnerable patient” was also
acknowledged, but this approach appears to be aimed at extremely high risk patients.
Conclusions from review of these recommendations and discussion were:
- Persons at intermediate risk have the greatest likelihood
of having their estimated risk altered by subclinical disease
testing.
- Tests should be chosen for clinical utilization based on availability,
reproducibility, evidence-base, and incremental value over
current office-based risk assessments.
- A clinical trial is needed to determine the clinical utility
of the tests available. A negative trial might serve to stem
over-utilization of unproven technology.
- No test has been definitively recommended for screening, because
there is no evidence that such testing improves clinical outcomes.
A low ABI (<0.90), however, has been recommended by National
Cholesterol Education Program as a “CHD equivalent.”
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Subclinical CVD and the Framingham Risk Score
Dr. Kronmal reviewed data from the Multi-Ethnic Study of Atherosclerosis (MESA), an ongoing multicenter
cohort study examining the relationship of subclinical CVD measures to each other, progression of
subclinical CVD, and the relationship of subclinical CVD to clinical CVD. The Framingham risk score was
most strongly related to coronary calcium and carotid IMT measures in both men and women, in the whole
cohort and in those at intermediate Framingham risk. He also presented data on ankle-brachial index, CRP,
and left ventricular mass from MRI.
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Subclinical Disease Testing: Study Design
Dr. Califf noted that the rate of growth of heart disease and expenditures for treatment during the next
several decades will be considerable, due to aging in the population. The number of Medicare enrollees is
expected to increase from 40 million in 2002 to 77 million in 2030. The Center for Medicare and Medicaid
Services (CMS) is beginning to put more emphasis on cost-effectiveness. Without evidence-based
guidelines, marketing of subclinical disease testing is untethered, and there is the potential for
enormous gaps to be created in utilization: third party payers will not pay for unproven procedures,
which will be obtained only by the economically advantaged.
The following hypothesis was submitted as the basis for a clinical trial: Subclinical disease testing
will improve patient outcome compared with current standard screening for CAD risk factors.
He proposed a design that randomized patients into testing vs. no testing, following a clinical
screen. Those who tested positive would be further randomized into aggressive vs. conservative
care, and the no test group would receive usual care. All groups would be followed for events.
Several issues were discussed:
- Feasibility of blinding of participants to test results
- The need to tailor the intervention to the test results.
- Feasibility of including one test vs. a battery of tests.
- Potential intensification of therapy in the control group.
- Additional comparison of aggressive vs. usual care among the
Test Positive group
- The need for intervention to be powerful enough to have an
effect, suggesting that treatment should be prescribed within
the trial.
Outcomes to be considered should include both morbidity and mortality, procedures and interventions,
psychological outcomes, including quality of life, costs, and changes in care in both intervention and
control groups. It was noted that subclinical disease diagnosis may lead to surgical interventions as
well. The issue of outcomes was discussed in more detail by Dr. Criqui (see below).
The consequences of not conducting a trial were considered: This would leave clinicians and patients
with no evidence base for making rational decisions regarding newly proposed, and sometimes expensive,
methods to identify and treat persons at high risk. The unrestrained growth of imaging services in the
community is of considerable concern. If testing is not an effective tool, such clinical testing
represents an enormous waste of expenditures. It was generally felt to be unlikely that the imaging
industry would fund a diagnostic efficacy trial in this arena.
Dr. Califf suggested that the potential costs and benefits of screening could be modeled using
existing data, an exercise that may be very informative although would be far less likely to be
accepted by the medical community than actual clinical trial results.
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Review of Subclinical Disease Measures
Coronary calcium. Dr. Raggi presented data on the association of coronary calcium, measured by
computed tomography, with traditional CVD risk factors, and its incremental value in predicting CVD risk
over that of traditional risk factors. Data from the South Bay Heart Watch, a cohort of adults who had at
least one risk factor, showed that a score of 300 or over effectively “moved” some persons at intermediate
risk into a high risk category. Data recently published by Shaw et al in 10,377 subjects screened with
EBCT showed that coronary artery calcium scores are predictive of all cause mortality and that they
provide incremental prognostic information over traditional risk factors. It would be useful to further
analyze these and similar data sets to determine the frequency of this occurrence. He recommended
employing age-specific cut points to determine high risk. Approximately half of persons at
intermediate risk may be expected to have scores of zero. This test is easy and well-tolerated,
and readings are highly reproducible. The scanning does involve low-dose radiation, and during
the discussion the problem of handling incidental findings, particularly lung nodules, was raised.
Coronary calcium is considered a likely candidate as a test to identify those at high risk.
During discussion, it was stated that consideration might also be given to including aortic calcium,
which has a much higher prevalence. Previous research has shown that aortic calcium on plain
abdominal films shows a strong independent association with CVD events.
C-reactive protein. Dr. Wilson reviewed considerations for a new risk factor, including the need for
standardized measurement, low variability, low correlation with existing risk factors, observational data
that demonstrate a relationship between the risk factor and outcomes, clinical trial data, improvement
in overall risk prediction, and measurement costs. Among several markers of inflammation, CRP appears
to meet more of these criteria than do other tests, such as fibrinogen. Overall, the association with
CVD is modest, however, particularly in relation to other risk factors. The AHA/CDC Panel concluded
that CRP is an independent marker of CVD risk and that in persons at intermediate risk (defined as 10-20%
over 10 years), hsCRP measurement may help direct further evaluation and primary prevention. The JUPITER
Trial is currently examining whether statins are beneficial in persons with low LDL and high CRP. He
recommended that CRP not be used as the basis for a new clinical trial.
Microalbuminuria. Dr. Flack presented NHANES data showing that the prevalence of microalbuminuria is
higher in women than men, is less than 10% among persons age 20-29 and increases to over 20% in persons
aged 80 and older. The prevalence is higher in African Americans and Hispanics than Whites. It is
associated with hypertension and diabetes and has been associated with all-cause and CVD mortality,
independent of other risk factors. ACE inhibitors can reduce albumin excretion. He recommended that
microalbuminuria be measured in a clinical trial but that it not be the basis for randomization to
treatment.
Carotid intima-media wall thickness (IMT.) Dr. O’Leary discussed the basis for measurement of carotid
IMT and showed the relationship of IMT to CVD. Among persons in the highest quintile of IMT, the age and
gender-adjusted 7-year CVD rates in CHS were approximately 25%, compared to approximately 5% in the lowest
quintile. IMT can be obtained in virtually all people, it is a continuous variable, and the procedure
has no risk. Standardized measurement is difficult, although a technician using a relatively inexpensive
machine in a physician’s office can probably categorize patients into low, medium and high. IMT is
considered a good candidate for consideration as a test to identify persons at high risk.
Ankle-brachial index (ABI). Dr. Criqui stated that ABI is simple and inexpensive to measure in a
reproducible manner. There is no risk to the procedure. The prevalence of an abnormal ABI, defined as
<0.9, ranges from 3% among those aged 45-64 to 27% among elderly men and women, in different studies.
Overall, the prevalence is likely to be <10% among persons at intermediate risk. Stress testing, such
as toe rises, can increase the sensitivity of the test. ABI is strongly predictive of CVD death, and
the current NCEP guidelines recommend that a low ABI be treated as a CHD risk equivalent. This would
complicate its inclusion as a basis for randomization in a trial, unless a borderline level or a
positive exercise test (e.g., toe rises) in persons with normal ABIs was included as a criterion for
a positive test.
Functional capacity. Dr. Lauer discussed treadmill stress testing for assessment of functional capacity,
which has been shown to discriminate well between persons at high and low risk for all-cause and
cardiovascular mortality. Worse functional capacity is correlated with older age, female gender, and
obesity, yet independently predicts death independent of the Framingham risk score. Furthermore,
functional capacity has been shown to identify those subjects most likely to benefit from aggressive
treatments like coronary bypass grafting. Testing must be symptom-limited, and age- and gender-specific
cut points for abnormality should be used. One problem is linking an effective intervention with low
functional capacity. While persons may improve functional capacity through exercise, this may be
difficult to accomplish. Exercise testing was not considered a candidate as a measure to identify high
risk patients in this trial. Nonetheless, it may have value as a baseline variable since, as with the
case with CABG, it may identify those people most likely to benefit from a screening strategy.
Left ventricular hypertrophy (LVH). Dr. Flack discussed methods for measuring LVH. The
electrocardiogram is insensitive and may overestimate the prevalence of LVH in African Americans.
Echocardiogram may be difficult to obtain in a large proportion of people, particularly the elderly,
and reproducibility is only fair. The prevalence of LVH increases with body mass index and blood
pressure and is higher in African Americans than Whites. Prevalence estimates range from 1% of young
White adults to 4% of young African American adults (CARDIA) to 28% of the middle-aged ARIC cohort.
The relative risk of CVD for LVH in the Framingham Study was approximately 1.5. Magnetic resonance
imaging provides much more reproducible measures of LV mass, but the cost is higher and many people
cannot tolerate or are excluded from the procedure. A measure of ventricular size may also be made
from cardiac CT scans. LVH was not considered a candidate test to identify high risk patients in this
trial but should be considered as a possible effect modifier of intervention.
Other measures. Dr. Herrington discussed the potential for genetic variants or genetic or protein
profiles to be used to identify high risk persons or to identify treatment responses. Individual
variants have generally been found to have small effects, but multiple variants in combination (genomics)
may have large effects. The costs of performing genetic scans and proteomics are currently high but are
declining. Vascular MRI, SPEC imaging, flow-mediated vasodilation, arterial stiffness, and CT
angiography may provide better opportunities for prediction in the future, but currently there is a
lack of data on predictive ability, high costs, unknown test characteristics, and limited
standardization.
During discussions, mild renal failure was noted to carry strong independent risk for CVD and may be
synergistic with other risk factors. Cystatin C appears to be a promising risk factor. Another point o
f discussion was the “street credibility” of the chosen test – that is, clinicians are more aware of and
likely to adopt some tests over others. From this perspective, there is relatively more interest in
coronary calcium, CRP, and carotid IMT than the other measures discussed.
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Clinical Screening Algorithms
Dr. Newman discussed the main goal of screening – to target more specific preventive treatment.
The screening test should identify high risk individuals among those initially deemed to be at
intermediate risk, and may be used to reinforce aggressive risk factor management and/or allow persons
defer treatment if their risk is estimated to be lower (therapeutic avoidance). Knowledge of the test
might enhance adherence to treatment.
The following considerations should be made in planning a screening strategy:
- Screening guidelines should be simple, clear, and easy for
people to understand. (The example of colonoscopy at age 50
was provided.)
- The screening algorithm should be able to be easily incorporated
into the health care system.
- A two-stage approach may be needed – first to establish “intermediate”
risk, then to refine with subclinical disease testing.
- Consider the need for age- and gender-specific thresholds
for testing and the need for repeat screening at some regular
interval (e.g., every 5 years).
- Screening tests should ideally have high sensitivity and specificity
to identify high risk persons, and should be low cost and
low risk.
Special consideration should be given to persons with chronic renal insufficiency, lupus, rheumatoid
arthritis, polycystic ovaries, type 1 diabetes, and other low prevalence conditions that are associated
with high risk. Age alone is a major factor; after age 65 in men and age 75 in women, the average risk
for CHD is >20% in 10 years. Consideration should also be given to defining intermediate risk as 10-20%
to assure a sufficient number of events in a trial. Dr. Newman recommended that for each test
considered, the sensitivity, specificity, cost, availability, reproducibility and risk be examined, but
that it appears that coronary artery calcium, IMT and perhaps CRP are the most likely candidates for
study.
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Population Considerations
Dr. Taylor addressed the question of treating global risk vs. risk based on individual factors.
He considered the arguments for and against including low or high risk persons in a clinical trial; the
intermediate risk approach appears to have the highest likelihood of clinical yield – that is, changing
the risk category of individuals based on test results. It is estimated that approximately 25% of
persons at intermediate risk could be re-classified based on coronary calcium results; thus, there
would be plenty of persons in this group for a study. The issue of studying whether therapeutic
avoidance is beneficial in persons classified as low risk based on test results was discussed; this
appears unfeasible as it would require abandoning current established guidelines. Also, according to
the South Bay Heart Watch data, persons at high Framingham risk remain at high risk, even if their
calcium scores are zero.
Consideration should be given to the gender composition of the population included in a trial, since
women are at lower Framingham risk than men. African Americans have a lower prevalence of coronary
calcium than Whites, and the risk associated with calcification in this group is not clear. However,
they should not be excluded.
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Interventions
Dr. Greenland proposed using a “polypill” – a combination of medications to lower blood pressure and
LDL-cholesterol, and possibly including aspirin – as the intervention for persons identified to be at
high risk. Aspirin does have a relatively high incidence of side effects, however. An alternative
would be to create complicated treatment guidelines based on individual risk factors, and treat to
specific blood pressure and LDL targets. Consideration should also be given to aggressive lifestyle
modification, as several types of dietary and exercise interventions have been shown to be as effective
as drug therapy in lowering blood pressure and modifying the lipid profile.
Outcomes
Dr. Criqui reviewed the possible outcomes that could be measured in a trial, either as primary or
secondary endpoints, or even as ancillary studies. These include:
- Risk factor change (obesity, physical activity, blood pressure,
etc.).
- Change in subclinical disease (coronary calcium, CRP, etc.).
- Morbidity, including CHD, cerebrovascular disease, peripheral
vascular disease, other CVD (CHF, in particular), and non-CVD
morbidity.
- Mortality, including fatal CHD, fatal cerebrovascular disease,
fatal peripheral vascular disease, fatal other CVD, and non-CVD
mortality.
- Quality of life, functional capacity, activities of daily
living, and psychosocial measures.
- Costs; cost-effectiveness.
Combined outcomes should be considered as a primary endpoint; total mortality is always the most
important hard clinical endpoint, however. Consider not only the number needed to treat to prevent one
event, but also the number needed to treat to harm one person. Finally, cost-effectiveness may be a
major trial result, particularly in the assessment of technology.
Based on the experience of other CVD intervention trials, this study is likely to require >10,000
subjects to test one type of screening test.
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Recommendations and Remaining Issues
The following recommendations and issues emerged during the meeting and the post-meeting conference
call regarding the motivation for and design of a clinical trial.
- Should the trial address whether testing reduces improves
outcomes or testing + intervention in those who test positive
improves outcomes?
- Working Group members and meeting attendees pointed
out the need to test both questions. Some proposed
an “encouragement” trial, whereby the test results
would be used to inform and perhaps serve as an incentive
for clinicians and patients to be more aggressive
(or perhaps less aggressive, in the case of negative
test results) in treatment to reduce CVD risk. Others
stated that such a trial would likely be negative
(i.e., find no benefit from screening), because there
are few guidelines regarding the appropriate clinical
response to positive tests, and clinical practice
is highly variable. The result would likely be only
modest differences in the actual treatment experienced
by patients between those at high risk vs. not at
high risk. Ideally, a trial would test both questions,
including a randomization to screening, to test the
effectiveness of screening, as well as randomization
to different levels of intervention among those who
test positive. It was also pointed out that it would
be desirable to determine if more aggressive treatment
without additional testing would be effective to improve
outcomes. There would be some efficiency realized
in testing more than one question in one study.
Several Working Group members noted that more aggressive
treatment will likely reduce CVD risk. The central
question is at what cost this risk reduction would
be achieved and whether a test and treat strategy
would have a more acceptable cost-benefit ratio than
alternative strategies.
- Which test(s) should be included as the basis for identifying
high risk people?
- The main candidates were coronary calcium and carotid IMT,
because these tests appear to be best at identifying persons
at higher risk. Factors such as cost, reproducibility, and
feasibility of measurement should be considered closely. A
separate consideration was the need to study technology such
as computed tomography in particular, because of its widespread
usage without a complete evidence base.
- Can test results be blinded?
- It was felt to be highly unlikely that test results could be
blinded, due to public interest in test results and ethical
considerations. Most other studies in the US have not been
able to blind the test results.
- Should the population included be at intermediate risk?
What other population characteristics should be considered?
- There was consensus that an intermediate risk group should
be the focus of a trial. The population should be broadly
representative, including women and minorities.
- If a prescribed treatment approach is used, what type of
intervention would be most appropriate?
- If treatment is prescribed by the trial, particularly pharmacotherapy,
consideration must be given whether to tailor treatment (i.e.,
treat to specific blood pressure and/or LDL-cholesterol goals)
or use a global risk approach, such as the “polypill.” Behavioral
measures to lower risk factors, such as diet and physical
activity, should also be considered. The possibility of providing
intensive treatment guidelines for test-positive patients
in the intervention group of a trial (an approach that is
between that of an “encouragement trial” and a prescribed
intensive intervention) was also raised. The trial design
must take into account current (at the time) clinical guidelines
and the possibility of near-term changes in guidelines. The
choice of interventions, particularly their effect sizes,
will influence sample size -- and ultimately, feasibility.
- Which outcomes should be included?
- Major morbid and mortal CVD outcomes and total mortality should
be the primary outcomes. Quality of life and costs must be
assessed. Cost-effectiveness assessment should be a major
goal, and could be considered a primary outcome in some design
scenarios. Physician and patient behavior should also be monitored,
particularly if the intervention is not prescribed.
- What would be the feasibility of a trial to answer these
questions?
- It was noted that a trial to address these questions would
likely be quite large and that delivery of intensive treatment
would be more expensive than an “encouragement” design. These
issues would need to be considered in determining what design
features would make a trial feasible.
The Institute will work with these recommendations to explore
possible trial designs. Ultimately, the decisions to conduct
a trial and the type of trial to conduct are driven by factors
of feasibility, including cost, as well as science and public
health. Working Group members may be consulted in the future
to provide more specific advice on trial design.
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References
Previous Recommendations for Subclinical CVD Testing
Smith SC, Greenland P, Grundy SM. AHA conference proceedings. Prevention V: Beyond secondary
prevention: Identifying the high-risk patient for primary prevention. Executive Summary.
Circulation 2000;101:111-116.
Greenland P, Smith SC, Grundy S.M. Improving coronary heart disease risk assessment in asymptomatic
people: role of traditional risk factors and noninvasive cardiovascular tests.Circulation.
2001;104:1863-1867.
Taylor AJ, Merz CN, Udelson JE. 34th Bethesda Conference: Executive summary--can atherosclerosis
imaging techniques improve the detection of patients at risk for ischemic heart disease?J Am Coll
Cardiol. 2003;41:1860-1862.
Greenland P, Abrams J, Aurigemma G, Bond M, Clark L, Criqui M, Crouse J, Friedman L, Fuster V,
Herrington D, Kuller L, Ridker P, Roberts W, Stanford W, Stone N, Swam J, Taubert K, Wexler L.
Prevention Conference V. Beyond secondary prevention: identifying the high-risk patient for primary
prevention. Noninvasive tests of atherosclerotic burden.Circulation 101, 111-116. 1-4-2003
U.S. Preventive Services Task Force. Screening for Coronary Heart Disease: Recommendation Statement.
Ann Intern Med. 2004;140:569-572.
Information on CVD Risk Distribution
Ford, ES, Giles WH, Mokdad AH. The distribution of 10-Year risk for coronary heart disease among U.S.
adults. Findings from the National Health and Nutrition Examination Survey III.Journal of the American
College of Cardiology 2004;43:1791-1796.
Greenland P, LaBree L, Azen SP et al. Coronary artery calcium score combined with Framingham Score
for risk prediction in asymptomatic individuals.JAMA. 2004;291:210-215.
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Working Group Roster
Working Group on Determining the Role of Subclinical Cardiovascular
Disease Testing in Patients at Intermediate Risk
Robert M. Califf, MD (Co-Chair)*
Professor of Medicine
Associate Vice Chancellor for Clinical Research
Duke Clinical Research Institute
Trent Drive, Box 3850
Durham, NC 27710
Phone: 919-668-8820
Fax: 919-668-7103
calif001@mc.duke.edu
Allen Taylor, MD (Co-Chair)*
Walter Reed Army Medical Center
6900 Georgia Avenue, NW
Building 2, Room 4A
Washington, DC 20307-5001
Phone: 202-782-2887
Fax: 202-782-7063
allen.taylor@na.amedd.army.mil
Michael Criqui, MD, MPH
University of California, San Diego
Stein Clinical Research Building
9500 Gilman Drive
Room 349La Jolla, CA 92093-5004
Site Phone: 858-534-3722
Office Phone: 858-534-3722
Alternate Phone: 858-534-8625
Fax: 858-534-8625
mcriqui@usd.edu
John Flack, MD, MPH
Professor and Associate Chair
Wayne State University
Department of Medicine
2E 4201 St. Antoine
Detroit, MI 48201
Phone: 313-955-0635
Fax: 313-993-0645
jflack@med.wayne.edu
Philip Greenland, MD*
Feinberg School of Medicine
Northwestern University
680 North Lake Shore Dirve
Suite 1102
Chicago, IL 60611
Office Phone: 312-908-1723
Fax: 312-908-9588
p-greenland@northwestern.edu
David Herrington, MD, MHS
Wake Forest University
School of Medicine
Department of Internal
Medicine/Cardiology
Medical Center Blvd.
Winston-Salem, NC 27157
Site Phone: 336-716-4950
Office Phone: 336-716-4950
Alternate Phone: 336-716-9124
Fax: 336-716-9188
dherring@wfubmc.edu
Richard Kronnal, PhD
Principal Investigator
University of Washington
Collaborative Health Studies
Coordinationg Center
Box 354922
Building 29, Suite 310
6200 NE 74th Street
Seattle, WA 98115-8160
Office Phone: 206-685-7123
Fax: 206-616-4075
Kronmal@u.washington.edu
Michael S. Lauer, MD, MPH
Director of Clinical Research and
Director of Stress
Laboratory, Desk F25
Cleveland Clinic Foundation
9500 Euclid Avenue
Cleveland, Ohio 44195
Phone: 216-444-3407
Fax: 216-444-6798
lauerm@ccf.org
Anne B. Newman, MD, MPH
Associate Professor of Medicine
and Epidemiology
Healthy Aging Research Program
Bellefield Professional Building
130 North Bellefield Avenue-Room 532
Pittsburgh, PA 15213
Phone: 412-383-1871
Fax: 412-383-1308
newmana@edc.pitt.edu
Daniel O'Leary, MD
tufts-New England Medical Center
Department of Radiology
750 Washington Street, Box 380
Boston, MA 02111
Site Phone: 617-636-8050
Office Phone: 617-636-8050
Alternate Phone: 617-636-0041
Fax: 617-636-0041
doleary@tufts-nemc.org
Paolo Raggi, MD
Tulane University
1430 Tulane Avenue SL-48
New Orleans, LA 70112
Phone: 504-588-5492
Charleston, SC 29425
Fax: 504-587-4237
praggi@tulane.edu
Peter W.F.Wilson, MD
Medical University of South Carolina
Medicine Division of Endocrinology
PO Box 250624
96 Jonathan Lucas Street
Charleston, SC 29425
Phone: 843-792-6245
Fax: 843-792-2601
wilsonpw@musc.edu
*participant on 7/23 conference call
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Planning Group Roster
Working Group on Determining the Role of Subclinical Cardiovascular Disease
Testing in Patients at Intermediate Risk
NHLBI Staff
Diane Bild, MD, MPH*
Telephone: 301-435-0457
E-mail: bidd@nhlbi.nih.gov
Lawton Cooper, MD, MPH
Telephone: 301-435-0419
E-mail: cooperls@nhlbi.nih.gov
Jeffrey Cutler, MD*
Telephone: 301-435-0413
E-mail: cutlerj@nhlbi.nih.gov
Michael Domanski, MD
Telephone: 301-435-0396
E-mail: domanskm@nhlbi.nih.gov
Teri Manolio, MD, Ph.D
Telephone: 301-435-0708
E-mail: manoliot@nhlbi.nih.gov
Merle Myerson, MD, EdD.
Telephone: 301-435-1290
E-mail: myersonm@nhlb.nih.gov
Christopher O'Donnell. MD
Telephone: 508-935-3435
E-mail: codonnell@nih.gov
Peter Savage, MD
Telephone: 301-435-0421
E-mail: savagep@nhlbi.nih.gov
Denise Simons-Morton, MD, Ph.D*
Telephone: 301-435-0384
E-mail: simonsd@nhlbi.nih.gov
Eser Tolunay, Ph.D.
Telephone: 301-435-0557
E-mail: tulunaye@nhlbi.nih.gov
Momtaz Wassef, MD
Telephone: 301-435-0550
E-mail: wassefm@nhlbi.nih.gov
*participant on 7/23 conference call
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of Contents
August 2004
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