Assessment of Coronary Artery Calcium in Active Duty Enlisted Military Members With 10 or More Years of Service
Conditions: Atherosclerosis, Plaque, Atherosclerotic
Sponsor: David Grant U.S. Air Force Medical Center

For Protocol Office use only: 
Protocol title: Assessment of Coronary Artery Calcium in Active Duty 
Enlisted Military Members with IO or More Years of Service 
FDG20130024H Protocol vl5 w Amend 9 
name redacted 6Feb20 
DGMC Human Research Protocol 
PROPOSAL FOR HUMAN RESEARCH 
CLINICAL INVESTIGATION FACILITY 
60th Medical Group (AMC) 
David Grant USAF Medical Center 
101 Bodin Circle 
Travis AFB, CA 94535-1800 
FWA00003321, DOD 50004, IRD00002726 
rxr evw 
APPROVE 
W/ AMD'""I 
AUG 3 0 2017 
60 MDG IRB 
TRAVIS AFB CA 
For assistance, call the IRB Coordinator at (phone # redacted 6Feb20 
1. Title of Investigation
Assessment of Coronary Artery Calcium in Active Duty Enlisted Military Members with 10 or
More Years of Service
2. Investigator and Investigation Staff
Name 
Rank 
name/contact 
info redacted 
6Feb20 
Capt 
Lt Col 
CTR 
CTR 
CTR 
CTR 
CTR 
Study 
Role 
PI 
AI 
SC 
SC 
CRN 
RA 
RA 
Date of 
Investigator 
Training 
30 Jun 15 
16 Feb 17 
16 Mar 16 
27 Apr 15 
19 Jun 17 
28Jan 16 
05 Aug 17 
Staff/ 
Dept/ 
DoD 
Resident/ 
Office 
Phone 
Assurance 
E-mail
Fellow 
Symbol 
Number 
Resident 
SGQX 
50004 
phone 
number 
redacted 
6Feb20 
Staff 
SGQX 
50004 
Staff 
SGSE 
Staff 
SGSE 
Staff 
SGSE 
Staff 
SGSE 
Staff 
SGSE 
email addresses redacted 
6Feb20
Medical Monitor (MM): Dr. Brad Williams 
3. Facility and/or Contractor
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For Protocol Office use only: 
Protocol title: Assessment of Coronary Artery Calcium in Active Duty 
Enlisted Military Members with IO or More Years of Service 
FDG20130024H Protocol vl5 w Amend 9 
name redacted 6Feb20 
DGMC Human Research Protocol 
All subject enrollment, data collection and data analysis will be conducted at David Grant US 
Air Force Medical Center, Travis Air Force Base, California. 
4. Purpose of Investigation
While the military is making strides towards improving the health and habits of service
members, there are many aspects of the military culture that negatively affect the cardiovascular
health of military members. Smoking/tobacco use, poor eating habits with MREs and ready
access to fast food establishments on base, inconsistent exercise, the socioeconomic status of
enlisted members and the stress of deployment are all factors that contribute to increased risk of
cardiovascular disease during military service. Currently the calculation of a patient's
Framingham risk score is the most commonly used method of calculating a patient's
cardiovascular risk, and this calculation is based on age, smoking history, blood pressure, and lab
values ·and compares it to a general population's risk. By the use of a cardiac CT scan, a
Coronary Artery Calcium (CAC) score can be calculated and used to estimate the degree of
atherosclerosis already present in each patient's coronary arteries, and thus establishing their risk
of future cardiovascular events. CAC scoring is a more patient-specific way of identifying
cardiovascular risk. The purpose of this study is to assess the prevalence of atherosclerosis in
enlisted military members with at least IO years of service and one or more cardiovascular risk
factor and to determine if their risk of a cardiovascular event is higher than predicted by the
Framingham score. If CAC scoring is demonstrated to be more accurate, particularly if it is
more likely tH detect risk, it may be used in the future to better risk stratify this population of the
military. The CAC results in patients could also be a motivating factor to create changes in the
military culture to attempt to mitigate these risks and create a healthier fighting force.
5. Category of Study and Risk Assessment
5.1. Category of Study 
D Medical Readiness D Prevention D Utilization Mgmt. D Managed Care I Diagnosisffreatment/Other
This study is placed in Diagnosis/Treatment/Other category as this will help better assess the risk 
each individual has of having a cardiovascular event in the future based on their Coronary Artery 
Calcium score. 
5.2. Proposed Risk: 
D Minimal Risk 
J Greater Than Minimal Risk 
This study is greater than minimal risk as a cardiac CT scan will be used, thus exposing the study 
subject to more radiation than on a typical day for that subject. 
6. Proposed Research
6.1. Background and Review of Literature: 
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For Protocol Office use only: 
Protocol title: Assessment of Coronary Artery Calcium in Active Duty 
Enlisted Military Members with 10 or More Years of Service 
FDG20130024H Protocol v l5 w Amend 9 
name redacted 6Feb20 
DGMC Human Research Protocol 
Coronary artery disease (CAD) is the leading cause of morbidity and mortality in the United 
States (1). LDL lipoproteins are positively associated with the development of coronary artery 
· disease. The most recognized guidelines for the screening and treatment of dyslipidemia for the
prevention of cardiac events are The National Cholesterol Education Program, Adult Treatment
Panel III (NCEP ATP III), published by the National Heart Lung and Blood Institute. These
guidelines focus primarily on LDL-C concentrations (2). The recommended treatment of
dyslipidemia for primary and secondary prevention of cardiac events consists of dietary and
lifestyle changes, lipir-specific pharmacotherapy with primarily HMG-CoA reductase inhibitors
(statins) and non-lipid agents such as aspirin. Specific goals for the initiating and targeting of
therapy are based on cardiac risk factors and the calculation of a Framingham Risk Score (FRS)
if indicated. Yet, approximately three-quarters of all "first-time'' myocardial infarctions occur in
individuals who would not have been eligible for pharmacotherapy with a statin or aspirin based
on the adopted risk stratification algorithm (3 ).
The FRS was developed by Wilson et al in 1998 and has become standard of care for estimating
risk of a cardiovascular event over the next 10 years. The estimation takes gender, age, smoking
status, systolic blood pressure, total cholesterol and HDL into account when predicting risk (4).
Scores are converted into percentage of risk over the next 10 years using a table created by
Wilson et al. Individuals with scores of 0-10% are considered low risk. A score of 11-15%
indicates low-moderate risk, while a score of 16-20% indicates mod-high risk. Those with scores
of>20% are considered high risk, while those with known coronary artery disease or acute
coronary syndrome are considered very high risk (2). While the FRS at times is a basis for
treatment decisions, this system of calculating risk is not individualized, and does not take into
account other contributing factors such as family history, weight, etc.
This concerning discordance between FRS scores and "first-time" myocardial infarctions has led
to the search for additional risk stratification tools for CAD to include novel biomarkers such as
high sensitivity C-reactive protein (hs-CRP), Brain Natriuretic Protein (BNP) and lipoprotein
subclasses, as well as imaging studies such as coronary artery calcium (CAC) screening with
computed tomography (Cardiac CT), carotid intimal medial thickness testing (CIMT) with
ultrasound and endothelial function assessment with brachia} artery ultrasound. Many of these
screening tools, when added to a FRS improve diagnostic accuracy. For instance, the Reynolds
risk score adds hs-CRP and family history (5). Coronary calcium is unique to these other
markers in that it is pathognomonic of coronary atherosclerosis (6). Multiple studies have shown
calcium scoring to be superior to FRS in diagnostic accuracy. A high calcium score increases
the risk of cardiac events greater than 10 fold. Conversely, a calcium score of zero has a
negative predictive value (NPV) of 99%. This translates into an area under the receiver-operator
curve (AUC) that increases from 0.67 with FRS to 0.75 for CAC in asymptomatic individuals
(7). The incremental accuracy is even more impressive in uncomplicated type 2 diabetics. The
AUC is 0.92 with CAC compared with 0. 74 using the United Kingdom Prospective Diabetes
Study Risk Score and 0.60 using the FRS (8). Despite the higher risk classification of type 2
diabetics, the FRS became less accurate in this study population, while the accuracy of CAC was
improved. This suggests a disproportionate discordance between traditional risk assessment
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For Protocol Office use only: 
Protocol title: Assessment of Coronary Artery Calcium in Active Duty 
Enlisted Military Members with 10 or More Years of Service 
FDG20130024H Protocol vl5 w Amend 9 
name redacted 6Feb20 
DGMC Human Research Protocol 
tools and actual events in the uncomplicated type 2 diabetic patient compared with unselected 
asymptomatic patients. 
CAC scores are reported as a numerical value and a percentage for age that is then regarded in 
terms of risk categories. A score of zero with no cardiovascular risk factors indicates no 
evidence of CAD and thus a very low risk of cardiovascular event in the next ten years. If the 
individual has cardiovascular risk factors with a CAC score of 0, they are considered moderately 
low risk. A score of 1-100 and a percentage for age percentile less than 75% indicates mild to 
moderate evidence of CAD and therefore indicates moderately high risk. A score of 101-399 or 
a percentage for age greater than 75% indicates moderate to high evidence of CAD and therefore 
is considered high risk with possible current partial blockage of coronary arteries. A score of 
>400 or any CAC score > 100 with a >90% percentage for age indicates extensive evidence of
CAD and thus high risk of cardiovascular event in the next ten years and could indicate further
testing is needed to address potential majority blockage (9, 10).
A consensus report issued by the American College of Cardiology and the American Diabetes 
Association emphasizes the concept of a global cardio metabolic risk. Factors that increase the 
risk of cardiovascular disease include dyslipoproteinemia, hypertension, diabetes and the 
prediabetic states such as insulin resistance or hyperglycemia, and central obesity. Smoking and 
sedentary lifestyle exacerbate the risk. The epidemic rise in the prevalence of one or more of 
these risk factors has created a heterogeneous population at risk that is perhaps not well 
represented by the traditional Framingham study population, which commenced in 1948. 
The American College of Cardiology (ACC) and the American Heart Association (AHA) 
recognize the incremental benefit of CAC screening and endorse its use in intermediate risk 
individuals with a FRS between 10-20%. The SHAPE (Screening for Heart Attack Prevention 
and Education) Task Force report goes further, publishing guidelines calling for the use of CAC 
scanning or CIMT as part of a nation-wide screening program to detect CAD in males 45 years 
and older, and females 55 years and older (10). 
Active duty military members are thought to be inherently healthier than their civilian 
counterparts due to the selection bias of health screening upon entry into the military. Webber et 
al. recently published a report in JAMA which showed a dramatic decline in the prevalence of 
atherosclerosis at the time of autopsy in US service members who died in the current conflicts in 
Iraq and Afghanistan, when compared to studies from the Vietnam and Korean War eras (11). It 
was suggested that there may be selection bias in an all-volunteer force, creating a "healthy 
warrior" phenomenon and that US service members today are healthier than in previous eras. 
Interestingly, in their study they found that "older age; lower educational level; higher BMI at 
military entrance; and prior diagnoses of dyslipidemia, hypertension, and obesity were associated 
with a higher prevalence of atherosclerosis." These risk factors are consistent with known risk 
factors for atherosclerosis. The study seems to demonstrate that service members dying in 
combat are not representative of the general U.S. population. However, in contrast to the 
conclusions drawn from this study, it also seems to demonstrate that these service members are 
not representative of the military population as a whole, either. 
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Protocol title: Assessment of Coronary Artery Calcium in Active Duty 
Enlisted Military Members with IO or More Years of Service 
FDG20130024H Protocol v15 w Amend 9 
name redacted 6Feb20 
DGMC Human Research Protocol 
While the United States, as well as the developed world is in the midst of an obesity epidemic, 
which brings with it the accompanying metabolic risk factors mentioned above, the military is by 
no means immune to this trend. According to the 2008 Department of Defense Survey of Health 
Related Behaviors Among Active Duty Military Personnel, the prevalence of "overweight" 
service members among active duty personnel, as defined by a body mass index (BMI) above 25 
kg/m2 was 60% overall. The trends for obesity, defined as a BMI of greater than 30 kg/m2, have 
likewise increased from 5% in 1995 to 12% in 2005, and 13% in 2008 (12). While it is true that 
the percentage of eighteen year-olds meeting the military' s height and weight standards has 
decreased, it is also true that eighteen year-old applicants tend to have a higher BMI than their 
counterparts in the general population, which seems to argue against a "healthy warrior" 
selection bias (13, 14). Despite the efforts of the military to enforce and encourage physical 
fitness, the prevalence of a medical diagnosis and visit for obesity increased 2.5 fold from 1998 
to 2008 (15). In addition, 15% of males and 20% of females reported difficulty meeting their 
service standard for weight and/or BMI (12). 
Smoking continues to be a problem for US service members. Despite a significant decline in the 
rates of smoking from 51 % in 1980 to 30% in 1998, it climbed to 34% in 2002 and has remained 
constant since that time. Likewise, the rates of heavy smoking declined sharply from 1980, but 
remained constant for the decade spanning 1998 to 2008. When compared to the civilian 
population, the overall rates are similar at 30% for military members vs. 29% for civilians. 
When broken down by age, the rates are higher for military members between the ages of 18-35, 
but lower between the ages of 36-64 when compared to civilians. When broken down by junior 
and senior officer and enlisted corps, the differences are striking; with rates of 40% among E 1-3 
vs. 10% among 01-3, and 21% among E7-9 vs. 5% among 04-10. 15% of all active duty 
military members initiated smoking after joining the military. And 30% of all current smokers 
began smoking after joining the military (12). Overall, the relatively high rate of smoking across 
the enlisted ranks suggests a culture of smoking throughout a military career that cannot be 
explained by adolescent recreational use. 
Dietary behaviors among US service members also appear to be less healthy than their civilian 
counterparts. In gathering data to promote the Healthy People 2010 objectives, the 2008 DOD 
health behaviors survey revealed that only 12.6% of all personnel reported consuming greater 
than 3 servings of fruit per day, compared to a civilian estimate of 28%. Only 14.2% of service 
members reported consuming greater than 3 servings of vegetables per day compared to a 
civilian estimate of 49% (12). In many cases US service members have limited access to food 
options especially earlier in their careers when they are required to live in dorms and receive 
food allowances at the base dining facilities. Meals Ready to Eat (MRE's) are provided to 
service members during training exercises and deployments. MRE' s contain on average of 1200-
1300 calories apiece, with a goal of service members consuming a total of 3800 calories per day. 
They are high in fat (36%) and carbohydrates (51 %) and low in protein (13%) and fiber (16). 
In an editorial accompanying the study by Webber et al, the author concluded "it is highly likely 
that the main finding of this study is valid: the prevalence of atherosclerosis in young men today 
is much lower than the prevalence in the Korean or Vietnam War eras. If these findings are 
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For Protocol Office use only: 
Protocol title: Assessment of Coronary Artery Calcium in Active Duty 
Enlisted Military Members with IO or More Years of Service 
FDG20130024H Protocol v15 w Amend 9 
name redacted 6Feb20 
DGMC Human Research Protocol 
generalizable to the US population as a whole, then the cardiovascular health of the US 
population may have improved appreciably over the past 6 decades (17)." 
It is tempting to conclude from this study that population health initiatives in the US, and more 
specifically the military, have led to a dramatic decline in rates of atherosclerosis in our younger 
population. It is also tempting to conclude that the current military lifestyle represents a model 
for healthy living and one that perhaps should be adopted by the US population as a whole. 
However, this conclusion is assuming that the warriors who died are both representative of the 
younger US population as a whole and the broader US military population, respectively. An 
alternative explanation for the findings by Webber et al. may be that the US service members 
accounting for the majority of deaths from combat and unintentional injuries are indeed 
healthier, but are not representative of the military community at large. Service members must 
undergo a thorough health and fitness screening process prior to each deployment. Members that 
do not pass are not deployable. Furthermore, within each service, there are additional screening 
measures for entry into occupations that are more likely to expose a service member to the risks 
of combat. The "healthy warrior" phenomenon, therefore likely exists only after multiple layers 
of screening, and is not likely present within the greater US military population. 
Based on the prevalence of obesity and accompanying cardiovascular disease risk factors 
mentioned above, the military population is unlikely to be much healthier than the age-matched 
US population. In fact, it may be that the rates of atherosclerosis in US service members are 
higher than in their civilian counterparts. It is quite possible that the environment and lifestyle of 
the military may both select for and exacerbate cardiovascular risk. The Prospective Army 
Coronary Calcium Project, as reported by Taylor et al, showed that traditional cardiac risk 
prediction tools significantly underestimate subclinical atherosclerosis in a low risk unselected 
screening cohort of 650 active duty Army personnel between the ages of 39-45 years of age (18). 
The prevalence of coronary calcium was 20.6% for males and 4.3% for females. In a 3 year 
follow up of 2000 subjects from this study, coronary calcium was associated with an 11.8 fold 
increase in cardiovascular events in males. There were no events in women in this study, likely 
due to low numbers. The study also deemed calcium scoring cost effective at $37,633 per 
quality-adjusted life year saved. 
Given that the true rates of atherosclerosis within the greater military population are unknown 
and that the cluster of cardio metabolic risk factors are present at a relatively young age and in 
greater numbers than the general population, we aim to study the prevalence of subclinical 
atherosclerosis in US enlisted service members with one or more cardio metabolic risk factor 
using coronary artery calcium scoring with cardiac computed tomography. While the military 
has not adopted the SHAPE Task Force guidelines, or any other screening protocol involving 
imaging based modalities, the value of using risk factors to select individuals who may stand to 
benefit from the greater predictive power of coronary artery calcium scoring may prove to be 
useful in this population. This approach could be key to understanding the prevalence of 
subclinical atherosclerosis, measuring the effect of population health initiatives on rates of 
atherosclerosis over time and ultimately improving our ability to meet the stated objective of 
DoD health promotion, which is to return the veteran back to society in relatively good health. 
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Enlisted Military Members with 10 or More Years of Service 
FDG20130024H Protocol vl5 w Amend 9 
6.2. Hypotheses or Research Questions or Objectives: 
name redacted 6Feb20 
DGMC Human Research Protocol 
Hypothesis: Enlisted military members with 10 or more years of service and at least one 
cardiovascular risk factor will demonstrate a higher risk of future cardiac events as assessed by 
coronary artery calcium scoring than the risk calculated by the Framingham Risk Score. 
The primary aims of this study are as follows: 
1) Determine prevalence of atherosclerosis in active duty enlisted military members with 10
or more years of military service and at least one cardiovascular risk factor using
coronary artery calcium scoring.
2) Assess the rate of reclassification of subjects from one risk category using Framingham
Risk Scores (FRS) to another risk category using the results of the Coronary Artery
Calcium (CAC) score.
3) Compare FRS to the CAC percentage for age risk score for enlisted subjects with at least
10 years of military service and at least one additional cardiovascular ris\ factor to
determine how well the results correlate with one another.
The secondary aims of this study are as follows: 
1) Compare CAC scores between each group in the following categories to see if there is
associations between these categories and formation of calcified plaques:
a. Those meeting the criteria for metabolic syndrome vs. those not meeting criteria
(See attachment 1 - Diagnostic Criteria for Metabolic Syndrome)
b. Those who lived in the dorms for >5 years compared to those living in the dorms
for<5
c.
Those with PT test failures vs. those without
d. Number of years of military service in the following groups: 10-14 years, 15-19
years 20-24 years and 25+ years
e.
Those with 1 risk factor vs. 2 risk factors, vs. 3 risk factors, vs. 4 risk factors, vs.
5 risk factors (as listed in the inclusion criteria section).
2) Compare FRS to CAC cardiovascular risk for each of the following categories:
a. Those meeting the criteria for metabolic syndrome vs. those not meeting criteria
b. Those who lived in the dorms for >5 years compared to those living in the dorms
for <5
c. Those with PT test failures vs. those without
d. Number of years of military service in the following groups: 10-14 years, 15-19
years 20-24 years and 25+ years
e. Those with 1 risk factor vs. 2 risk factors, vs. 3 risk factors, vs. 4 risk factors, vs.
5 risk factors (as Hsted in the inclusion criteria section)
6.3. Relevance/Significance: 
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For Protocol Office use only: 
Protocol title: Assessment of Coronary Artery Calcium in Active Duty 
Enlisted Military Members with 10 or More Years of Service 
FDG20130024H Protocol vl5 w Amend 9 
name redacted 6Feb20 
DGMC Human Research Protocol 
•
One of the mottos of the military medical corps is to preserve the fighting force. This
concept is essential to the military branches accomplishing their missions. Through
public health information and research studies, the military is pushing to change the
military culture to support a healthier active force, thus leading to a healthier retiring
population. Recognizing the need for further change in the military culture could lead to
new policies and support for military members that could reduce the risk of
atherosclerosis and heart disease in the future. Of those that died in combat in the
Iraq/ Afghanistan conflicts, 8.5% demonstrated evidence of atherosclerosis on autopsy
(9). Due to higher smoking rates, obesity, MRE consumption, access to fast food on base
and stress of deployments, enlisted military members with more than 10 years of military
service will likely demonstrate a higher prevalence of atherosclerosis. Understanding the
prevalence in this group could lead to changes in health initiatives and could lead to
further studies in the future that use CAC scoring to measure the effect of new population
health initiatives over time.
•
For the subjects enrolled in this study, learning about their personalized cardiovascular
risk could motivate life style changes that may decrease their likelihood of having a
significant cardiac event in the future. This could greatly improve their quality of life,
potentially prolong their lives and decrease costs of healthcare over time.
6.4. Research Design and Methods: 
•
Design:
o
This study is designed to be an observational study to determine the prevalence of
atherosclerosis in enlisted military members with 10 or more years of service.
The study is also designed to determine if coronary artery calcium scoring
predicts higher or lower cardiovascular risk scores for enlisted military members
with 10 or more years of service than the Framingham risk score predicts. (See
flow diagram below).
•
Methodology:
o
Recruitment: (See Recruitment section 6. 7 below for more information).
o
Enrollment/Consent: (For flow of the subject through the study, this section is
briefly mentioned here, for more in-depth details please see the consent
description in section 6. 7 below.)
•
Subjects interested in the study will meet with a study coordinator or other
team member who has been trained on the study/consent process to
undergo the consent process. The study team member enrolling the
subject will have the subject sign a HIP AA authorization prior to initiating
the interview. (See attachment 2- HIPAA Authorization). The study
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Protocol title: Assessment of Coronary Artery Calcium in Active Duty 
. Enlisted Military Members with IO or More Years of Service 
FDG20130024H Protocol vlS w Amend 9 
name redacted 6Feb20 
DGMC Human Research Protocol 
team member will then have the subject fill out the front portion of the 
initial interview/questionnaire and the study team member will fill out the 
back portion (See attachment 3 - Initial Interview/Questionnaire). At this 
time if the subject meets inclusion/exclusion criteria (See attachment 4 -
Inclusion/Exclusion Criteria Checklist), the study team member will 
consent the subject for participation in the study. (See attachment 5 -
Informed Consent Document). 
o
Data Collection: At the same appointment after consent is obtained, the study
team member will provide the subject with a study packet to include a copy of
their HIP AA Authorization, their Informed Consent Document, and a patient
handout about what to expect for the cardiac CT for CAC scoring. (See
attachment 6 - Patient Handout on Cardiac CT). The study team member will
then take the subject's blood pressure and waist measurement. Blood pressure
will be taken on the right arm with feet/legs uncrossed and the subject in a seated
· position for at least 5 minutes. The waist measurement will be completed as
defined by Air Force physical fitness testing standards, one inch above the iliac
crest and parallel to the ground. The study team member will then check the
subject's AHLTA record to determine if hemoglobin AlC and/or lipid panel have
been drawn in the past 3 months. If these labs have been drawn they will record
them on the back portion of the initial interview. If the labs have not been drawn
in the past 3 months, the study team member will order the required labs in CHCS
and instruct the subject to proceed to the lab when fasting.
o
Verification of Interview: After the initial encounter, a study team member will
confirm with AHL TA record if the subject has a diagnosis of hypertension,
diabetes or pre-diabetes and ensure this information matches the information
provided on the initial interview. A study team member will also verify that the
subject has no documented history of Coronary Artery Disease (CAD), Coronary
Artery Bypass Grafting (CABG), Myocardial Infarction (Ml), or Percutaneous
Intervention/Stent Placement (PCI) or significant radiation exposure in the past 12
months (see exclusion criteria).
o
Initial Labs: If HgbAlC and a lipid panel have not been drawn in the past 3
months, the subject will be sent to the lab for initial blood work. The HgbA 1 C
lab will help establish if the subject is diabetic/pre-diabetic, and if the subject is a
known diabetic will help determine how well their diabetes is controlled. The
lipid panel will help establish if the subject has dyslipidemia/hyperlipidemia. A
recent (within 3 months) HDL and Total Cholesterol value are needed directly for
calculating the Framingham risk score. Labs will be ordered by the study
coordinator or AI using an order set in CHCS marked as "for research purposes".
•
HgbAlC: Will be drawn as per normal lab protocol. Results will be
recorded in CHCS.
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DGMC Human Research Protocol 
•
Lipid Panel: Will be drawn as per normal lab protocol including HDL
measurement, Triglyceride measurement and total cholesterol
measurement. The LD L will be calculated using the Friedewald equation
(standard equation used by labs to determine LDL without having to
directly measure LDL- this is how LDL is resulted when a "lipid panel"
is ordered). The Non-HDL will be calculated by subtracting HDL from the
total cholesterol measurement. Results will be reported in CHCS.
o
CT scan: A cardiac CT for Calcium Scoring will be ordered in CHCS with "CAC
Study Participant" noted in the comment section. Radiology will then walk the
subject in the same day if space is available, or the radiology front desk will
schedule the subject for a future date/time. Prior to CT scanning, all subjects will
fill out the standard questionnaire that radiology provides that includes a question
for females about the possibility of being pregnant. All females who answer yes to
this question will be dropped from the study. Subjects will be scanned on a
Siemens 128 slice multi-detector CT. A cardiac CT trained technologist from the
department of Radiology will scan the subject. A cardiothoracic radiologist will
interpret the studies. Cardiac CT for Coronary Artery Calcium scoring is not
considered standard of care unless a patient has a Framingham risk score between
5-20% to greater characterize risk. Some subjects in this study may have a
Framingham risk <5%. (Please see section 6.5 and 6.8 below for more
information on incidental findings and radiation exposure.)
o
CT Scan Methodology: Coronary artery calcium (CAC) examinations will be
performed by certified radiology technologists using a 128 multi-detector
computed tomography (MDCT) scanner (SOMATOM Definition Flash second
generation, 2x64, Siemens AG, Erlangen, Germany). Images will be obtained
using 40- to 50-slice (3mm thickness) protocol with prospective image acquisition
triggered to 60% to 80% of the electrocardiographic RR interval with suspended
respiration. Off-line reconstructions of the images will be performed on syngo
Acquisition Workplace Calcium Scoring (software version 201 lA).
o
Interpretation of CT Scan: After CT scan, the cardiothoracic radiologist will
read the images to determine the coronary artery calcium scoring using the
following method:
•
A focus of coronary calcium will be defined as the presence of four or
more contiguous pixels with> 130 Hounsfield units. Total and per-vessel
(right coronary artery, left main coronary artery, left anterior descending
branch and left circumflex branch) CAC burden will be assessed by the
cardiac radiologist using the Agatston scoring method.
o
Follow-Up: Scan results with CAC scores will be read within 10 days after the
CT scan. The research coordinator or other study team member will be alerted
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Protocol title: Assessment of Coronary Artery Calcium in Active Duty 
Enlisted Military Members with 10 or More Years of Service 
FD020130024H Protocol v15 w Amend 9 
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DGMC Human Research Protocol 
when results are placed in CHCS. When results are available, the research 
coordinator will review the results. Follow-up plan will depend on CAC score: 
•
For CAC score of zero (0): Subject will be informed of their score via a
results letter that explains the meaning of the score, explains their
Framingham Risk Score and provides results of the initial lab work that
was drawn (See attachment 7 -Results Letter). These letters will be
produced on an individual case basis and mailed to study subjects. If
subjects in this category are noted to have abnormal HgbA 1 C and/or lipid
panel their primary care manager (PCM) will be notified of aonormal
results via encrypted e-mail.
•
For CAC scores of 1-400: The study coordinator or other research team
member will place a consult/referral into CHCS to the Metabolic Clinic
with the words "CAC results follow-up" in the description section. At this
time a telephone-consult will be placed in the subject's AHLTA record
(See attachment 8 -Telephone Consult Template) and their PCM will be
notified via an encrypted e-mail of the subject's CAC results and their
referral to the metabolic clinic (See attachment 9 -PCM Notification E­
Mail Template). If subjects in this category are noted to have abnormal
HgbA 1 C and/or lipid panel their primary care manager (PCM) will be
notified of abnormal results via encrypted e-mail. The Metabolic Clinic
will see these referrals and have the HL&VC receptionist call the subject
to directly schedule a follow-up appointment. The follow-up appointment
will be within 60 days of the CAC scan. If subjects fail to attend their
follow-up appointment, they will be contacted by a member of the study
team to remind them of the importance of following up. The -research
coordinator will ensure subjects attend follow-up as scheduled, and will
document whether they have followed up in the subject's study chart. At
the follow-up appointment, the following will be discussed:
•
Coronary Artery Calcium Score Results
•
Framingham Risk Score
•
What the two scores mean
•
Lab Results
•
Lifestyle changes that can be made to decrease risk, i.e. smoking
cessation, increasing exercise, dietary changes, etc.
•
For CAC >400: The study coordinator or other research team member
will place a referral into CHCS to the cardiology clinic for further
evaluation. At this time a telephone-consult will be placed in the subject's
AHL TA record (See attachment 8-Telephone Consult Template) and
their PCM will be notified via an encrypted e-mail of their CAC results
and their referral to cardiology (See attachment 9-PCM Notification E­
Mail Template). If subjects in this category are noted to have abnormal
Form Revised as of25 July 2012 
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For Protocol Office use only: 
Protocol title: Assessment of Coronary Artery Calcium in Active Duty 
Enlisted Military Members with 10 or More Years of Service 
FDG20I30024H Protocol v15 w Amend 9 
name redacted 6Feb20 
DGMC Human Research Protocol 
HgbA 1 C and/or lipid panel their primary care manager (PCM) will be 
notified of abnormal results via encrypted e-mail. The HL& VC will 
contact the subject to schedule a follow-up appointment for the subject to 
be seen within 30 days, but no later than 60 days of the CAC scan. At the 
cardiology follow-up appointment, the following will be discussed: 
•
Measurements:
•
Coronary Artery Calcium Score Results
•
Framingham Risk Score
•
What the two scores mean
•
Lab Results
•
Lifestyle changes that can be made to decrease risk, i.e. smoking
cessation, increasing exercise, dietary changes, etc.
•
Medications that could reduce risk of cardiac events in the future
•
Interventions, imaging or further testing that may be necessary to
further evaluate/treat the subject
o
Framingham Risk Score - (See attachment 10 - Framingham Risk Calculation
Tables), includes age, systolic blood pressure;HDL level, Total Cholesterol level
and smoking status
o
HgbAl C (if not previously tested within 3 months prior to study enrollment)
o
Lipid Panel (if not previously tested within 3 months prior to study enrollment)
o
Coronary Artery Calcium Score
o
Waist Circumference
o
Blood Pressure
•
Demographic Info to be Collected:
o
Branch of Military Service
o
Rank
o
Number of Years of Military Service
o
Number of Deployments >2 months
o
Number of Years living on base in Dormitories
o
Number of PT test failures
o
Number of Cardiac Risk Factors (Tobacco use, Diabetes, pre-diabetes,
hypertension, waist circumference, hyperlipidemia)
6.5. Intervention/Treatment: 
•
Subject will undergo one cardiac CT scan. Appointment for scan will take 10-20 minutes, the
majority of which will be subject check in and positioning. Average radiation exposure for a
CAC CT is 0.89 millisieverts (mSv). For context, the average population radiation exposure
from background is approximately 3.11 mSv at sea level (4.5 mSv at high altitude), meaning
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For Protocol Office use only: 
Protocol title: Assessment of Coronary Artery Calcium in Active Duty 
Enlisted Military Members with IO or More Years of Service 
FDG20130024H Protocol vl5 w Amend 9 
name redacted 6Feb20 
DGMC Human Research Protocol 
that the dose from this study is less than half of a person's baseline annual dose from sources 
such as cosmic radiation. Furthermore, a mammogram is approximately 0.73 mSv. 
o
Incidental Findings: As per usual radiology operating procedure, all cardiac CT
scans will be reviewed in their entirety for any abnormalities. The report will be
placed in CHCS/AHLTA and can be reviewed by the subject's primary care
physician. The radiologist reading the films will also make follow-up
recommendations for any concerning abnormal findings. The abnormalities will
be brought to the attention of the provider who orders the cardiac CT. That
provider will then inform the PI or AI of any abnormal findings. The PI/ AI will
then inform the subject of these findings as well as the follow-up
recommendations of the radiologist. An encrypted e-mail will be sent to the
subject's primary care physician if incidental findings are discovered.
Study Flow Chart (displayed on following page): 
Form Revised as of25 July 2012 
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For Protocol Office use only: 
Protocol title: Assessment of Coronary Anery Calcium in Active Duty 
Enlisted Military Members with 10 or More Years of Service 
FDG201300241-1 Protocol v 15 w Amend 9 
6.6. Data Collection/ Analysis: 
Sample Size/Power Analysis 
name redacted 6Feb20 
DGMC Human Research Protocol 
•
Based on an 8.5% expected prevalence of atherosclerosis in the active duty military
population, the sample size requirement for a 95% confidence interval for a proportion
of+/- 0.05 is 120 subjects. As the prevalence among active duty with> 10 years of
military service and at least one cardiovascular risk factor is likely higher, for this
study the estimated prevalence is 10%. The sample size requirement for a 95%
confidence interval for a proportion+/- 0.05 with a prevalence of 10% is 138 subjects.
For this study, anticipated failure of completion/drop out is estimated to be
approximately 10%, so 150 male volunteers will be recruited to achieve this
confidence interval for prevalence of active duty atherosclerosis in enlisted members
Form Revised as of25 July 2012 
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For Protocol Office use only: 
Protocol title: Assessment of Coronary Artery Calcium in Active Duty 
Enlisted Military Members with 10 or More Years of Service 
FDG20130024H Protocol vlS w Amend 9 
name redacted 6Feb20 
DGMC Human Research Protocol 
with 10 or more years of military service. Females do not tend to demonstrate 
coronary artery calcium in the same manner/degree as males. Therefore an additional 
pilot sample of 30 female volunteers will be used to assess the prevalence detected in 
the female active duty population. 
Data Analysis 
•
Primary Aims:
o
Determine prevalence of atherosclerosis in active duty enlisted military members
with 10 or more years of military service using coronary artery calcium scoring.
•
A 95% confidence interval will be calculated for the observed prevalence
in the active duty population.
o
Assess the rate of reclassification of subjects from one risk category using
Framingham Risk Scores (FRS) to another risk category using the results of the
Coronary Artery Calcium (CAC) score.
•
For the purposes of this study, the SHAPE guidelines will be used to
classify the CAC scores and percentage by age into the following
categories:
•
Low Risk: CAC of O and no cardiovascular risk factors
•
Low-Moderate Risk: CAC of O with cardiovascular risk factors
•
Moderate-High Risk: CAC 1-100 and percentile for age <75%
•
High Risk: CAC 100-399 or percentile for age >75%
•
Very High Risk: CAC >100 and percentile for age >90% or CAC
>400
•
For the purposes of this study, the FRS percentages will be classified into
the following categories:
•
Low Risk: FRS 0-10%
•
Moderate Risk: FRS 11-15%
•
Moderate-High Risk: FRS 16-20%
•
High Risk: FRS >20%
•
Very High Risk: Acute Coronary Syndrome or known Coronary
Artery Disease or significant multiple risk factors
This study will assess the rate at which CAC scoring reclassifies the FRS of a subject to a 
different risk category. To do so a descriptive table will be used to demonstrate the changes 
seen. The net reclassification improvement (NRI) will be calculated to describe further the 
amount of reclassification that is accomplished by using the CAC scoring method (19). Please 
see reference 19 for more information. 
o
Compare the Framingham Risk Score (FRS) to the Coronary Artery Calcium
(CAC) score for enlisted subjects with at least 10 years of military service to
determine how well the results correlate with one another.
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For Protocol Office use only: 
Protocol title: Assessment of Coronary Artery Calcium in Active Duty 
Enlisted Military Members with IO or More Years of Service 
FDG20130024H Protocol vlS w Amend 9 
name redacted 6Feb20 
DGMC Human Research Protocol 
•
Linear Regression model will be used to determine if the FRS score
correlates with the CAC score.
•
Secondary Aims:
o
A t-test will be used to compare CAC scores between each group in the following
categories to see if there are associations between these categories and formation
of calcified plaques:
•
Those meeting the criteria for metabolic syndrome vs. those not meeting
criteria (See attachment 1 - Diagnostic Criteria for Metabolic Syndrome).
•
Those who lived in the dorms for >5 years compared to those living in the
dorms for <5.
•
Those with PT test failures vs. those without.
o
Analysis of Variance (ANOV A) and/or Logistic regression will be used to
compare CAC scores between each group in the following categories to see if
there are associations between these categories and formation of calcified plaques:
•
Number of years of military service in the following groups: 10-14 years,
15-19 years 20-24 years and 25+ years
•
Those with 1 risk factor vs. 2 risk factors, vs. 3 risk factors, vs. 4 risk
factors, vs. 5 risk factors (as listed in the inclusion criteria section).
o
The correlation between CAC and FRS scores will be described using multiple
linear regression for the following categories:
•
Those meeting the criteria for metabolic syndrome vs. those not meeting
criteria.
•
Those who lived in the dorms for >5 years compared to those living in the
dorms for <5.
•
Those with PT test failures vs. those without.
•
Number of years of military service in the following groups: 10-14 years,
15-19 years 20-24 years and 25+ years.
•
Those with I risk factor vs. 2 risk factors, vs. 3 risk factors, vs. 4 risk
factors, vs. 5 risk factors (as listed in the inclusion criteria section).
Source of Research Material per Participant: 
Source of Research Material per Participant 
Standard Care 
Research Driven 
Blood Sample - Hgb A IC 
0 
I **
Blood Sample - Lipid Panel 
0 
1 ** 
Cardiac CT Scan 
0 
1
Outpatient Record Review 
0 
1
Subject Interview 
0 
1 
Demographics 
0 
1 
** In some subjects, the labs could be standard of care, but since the labs will not be
standard of care for all subjects, they are listed here as research driven.
Form Revised as of 25 July 2012 
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Page 16 of29 

For Protocol Office use only: 
Protocol title: Assessment of Coronary Artery Calcium in Active Duty 
Enlisted Military Members with 10 or More Years of Service 
FDG20130024H Protocol v15 w Amend 9 
name redacted 6Feb20 
. DGMC Human Research Protocol 
6.7. Subject Population 
Age Range: 
[gl e 18 y/o 
[gl Male 
D Children ( < 18) 
[gl Female 
Sex: 
Vulnerable Population: 
f No 
D Yes ( explain) 
•
Children, pregnant women, fetuses, neonates, mentally disabled, and prisoners will not be
used in this research study as the population this study is looking at military members
with at least IO years of service. Any females identifying that they may be pregnant will
be excluded from the study.
Number of Subjects: 
•
Total Number of Subjects (nation-wide/study-wide): _180_
•
Number of Subjects Planned for DGMC: _180_
•
Number of Subjects Planned for (Specify Institution): _O_
Inclusion/Exclusion Criteria: 
•
Inclusion Criteria:
o
Active Duty Military Members with at least 10 years of service
o
Enlisted Rank
o
Males 35 years and older OR Females 45 years and older (please note the age
difference is due to the fact that female plaque formation with calcification has
been shown to lag that of males by about 10 years)
o
One or More of the Following Risk Factors:
•
Smoker - at least 5 pack years in the past 5 years (pack year = number of
packs per day * number of years of smoking)
•
Diabetic (Fasting glucose of >125 mg/dL on two or more blood draws, or
Random Blood Glucose of >200 mg/dL on a single blood draw, or
HgbAlC >6.5%, or previous diagnosis of diabetes listed in the subject's
medical record) or Pre-diabetic (Fasting glucose > 100 on two or more
blood draws or HgbA 1 C 5. 7-6.4)
•
Hypertension (SBP > 140 or DBP >90 or on blood pressure medications
or diagnosis of hypertension in medical record)
•
Waist Circumference> 40 inches for males or >35 inches for females
•
Hyperlipidemia (LDL> 130, HDL<40 for males, HDL <50 for females,
Triglycerides >200, on lipid lowering medications and/or diagnosis of
hyperlipidemia in medical record)
•
Exclusion Criteria:
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For Protocol Office use only: 
Protocol title: Assessment of Coronary Artery Calcium in Active Duty 
Enlisted Military Members with IO or More Years of Service 
FDG20130024H Protocol v15 w Amend 9 
o
Males <35 years old
name redacted 6Feb20 
DGMC Human Research Protocol 
o
Women <45 years-old (please note the age difference is due to the fact that female
plaque formation with calcification has been shown to lag that of males by about
10 years)
o
Officer Rank-officers are excluded as we are looking at the enlisted culture in
the military.
o
History of any of the following:
•
Coronary Artery Disease (CAD)
•
Coronary Artery Bypass Grafting (CABG)
•
Myocardial Infarction (MI)
•
Percutaneous Intervention/Stent Placement (PCI)
•
Angina -cardiac chest pain
•
Radiotherapy ( external beam, brachytherapy, radiopharmaceutical)
o
Under the care of any of the following types of providers in the past 12 months
(As these subjects are at greater risk of having had significant radiation exposure
to the chest over the past 12 months):
•
Radiation/Medical Oncologist
•
Interventional Radiologist
•
Cardiologist
•
Cardiothoracic Surgeon
•
Vascular Surgeon
o
Females who think they may be pregnant
o
Pregnant females
Recruitment: 
•
Fliers- Will be posted throughout the Heart, Lung & Vascular (HL&VC), Family
Medicine,' Family Health, Internal Medicine and Flight Mfdicine clinics, DGMC
cafeteria, elevators and other public areas of DGMC. Advertisement posters/fliers will
also be posted in other public buildings on Travis AFB in order to ensure recruitment of a
population representative of the active duty population at Travis AFB. Research
coordinators may also sit near advertisement posters in the HL&VC waiting room and
cafeteria to answer any potential participant's questions. (See attachments 11 & 12 -
Recruitment Fliers-landscape and portrait).
•
Pamphlets -Will be placed in the waiting rooms of primary care clinics, and to be given
out by primary care providers and PHA administrators who identify members with more
than 10 years military service. (See attachment 13 -Recruitment Trifold Pamphlet).
•
First Sergeant Distribution -First Sergeants will be notified of the study via a flier e­
mailed to them or via presentation by a study team member at the First Sergeant's
meeting. They will be asked to pass the flier on by e-mailing it out to their enlisted
personnel as an FYI, and/or by posting it in their work spaces and break rooms for their
squadron.
Form Revised as of 25 July 2012 
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For Protocol Office use only: 
Protocol title: Assessment of Coronary Artery Calcium in Active Duty 
Enlisted Military Members with IO or More Years of Service 
FDG20130024H Protocol v15 w Amend 9 
name redacted 6Feb20 
DGMC Human Research Protocol 
•
E-mail/Newspaper-The research team may elect to advertise the study via e-mail sent
out by wing and hospital public affairs offices. The research team may also elect to
advertise via Air Force newspaper publications or other military newspapers at
surrounding bases. (See attachment 14- Recruitment Research Announcement).
--- If these methods fail to produce the number of subjects needed within 3 months, the
following recruitment methods may be used:
•
Presentation at Transition Assistance Program (TAP) Course - A member of the
research team will give a brief presentation at each TAP course, which is mandatory for
all military personnel who anticipate separation or retirement within 1 year. Presenter
will follow attached script and answer any questions that may arise. (See attachment 15 -
Recruitment Script for TAP Course).
•
Information table outside TAP Course - A member of the research team will man a
table located outside the TAP course classroom during lunch break and/or at the end of
the day to distribute informative pamphlets and answer questions about the study. These
pamphlets are the same as mentioned above.
•
Retirement Physicals - The research team may elect to advertise in clinics where
retirement physicals are conducted via pamphlets and educating physicians about the
ongoing study. These potential subjects will be identified by contacting clinic nurse
managers in Family Medicine, Family Health, Flight Medicine and Internal Medicine.
•
Presentation at Smoking Cessation Classes - A member of the research team will give
a brief presentation about the CAC study at each smoking cessation class similarly to the
TAP course presentations. Fliers/pamphlets may be handed out at these classes.
•
EMR chart review - Upcoming appointments at DGMC will be reviewed for
inclusion/exclusion criteria. If patient fits study criteria they will be contacted via
telephone or in person, before or after scheduled clinic appointment.
•
Briefing Presentations: Members of the research teams may advertise the study at a
number of briefing opportunities across Travis AFB where potential qualifying
candidates may attend. This includes, but is not limited to: briefings for PTLs at the gym,
classes provided in Nutritional Medicine, or the AFRC Newcomer's Information Fair.
•
Hospital Marquee: The research team may elect to advertise the study via the hospital
marquee to reach a wider pool of potential candidates.
•
Online Announcements: The research team may advertise the study on any Travis AFB
approved sites including, but not limited to: the SharePoint home page and DGMC News
+ Notes
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For Protocol Office use only: 
Protocol title: Assessment of Coronary Artery Calcium in Active Duty 
Enlisted Military Members with 10 or More Years of Service 
FDG20130024H Protocol v15 w Amend 9 
Consent: 
name redacted 6Feb20 
DGMC Human Research Protocol 
•
Subjects that have expressed interest in the study will be scheduled for an informed
consent review/initial visit at the Clinical Investigation Facility (CIF). The subject will
be brought to a private exam room or office where they will be individually consented by
the research coordinator, the PI or other research team member that has been trained on
the protocol. The study team member will explain the nature and scope of the study,
discuss potential risks and benefits of participation, answer questions for the subject and
ensure the subject fully understands informed consent. The study will be explained to the
subject in lay terms. At least one hour of study staff time will be set aside for each
participant to receive information, ask questions and consider participation in the study.
The subject may elect to discuss the study with others if they so choose, prior to agreeing
to participate. If the subject agrees to participate, the IRB approved informed consent
document and the Health Insurance Portability and Accountability Act (HIP AA)
Authorization Form will be signed and personally dated by the subject and investigator or
study staff that have been delegated responsibility and have been trained on the protocol.
A copy of the signed consent form will be made and provided to the subject. The original
signed consent form will be turned into the protocol office and a copy will be placed in
the subject's study folder and stored with other protected health information in a locked
filing cabinet in an office that is locked when the office owner is not in the room. A copy
of the ICD will be placed into their electronic medical record as well. Subjects will be
assured that they may withdraw from the study at any time and for any reason and their
medical treatment will not be compromised. Research procedures will not start until the
IRB approved informed consent document has been signed and dated by the subject and
research team member who has been delegated responsibility for consenting subjects and
has been trained on the protocol.
6.8. Risks/Benefits: 
•
Risks:
o
Exposure to Radiation: For a working population composed of both sexes, the
lifetime risk of fatality from cancer is 4% per sievert (Sv) for the type of radiation
used in a CAC CT. As mentioned previ.ously, average radiation exposure for a CAC
CT is 0.89 milisieverts (mSv). For context, the average population radiation exposure
from background is approximately 3 .11 mSv at sea level ( 4.5 mSv at high altitude),
meaning that the dose from this study is less than half of a person's baseline annual
dose from sources such as cosmic radiation. Furthermore, a mammogram is
approximately 0.73 mSv.
o
Emotional Response to/Stress Due to Results: Some subjects may have results that
indicate a high risk of a cardiovascular event in the future. This news could be
emotionally stressful to the individual, however knowing their cardiovascular risk
could lead to improved quality of life long term.
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For Protocol Office use only: 
Protocol title: Assessment of Coronary Artery Calcium in Active Duty 
Enlisted Military Members with 10 or More Years of Service 
FDG20130024H Protocol vl5 w Amend 9 
name redacted 6Feb20 
DGMC Human Research Protocol 
o
Incidental Findings: There is a possibility that while reviewing the cardiac CT scan
that the radiologist may discover an abnormality not related to the study. If this
occurs, the radiologist will follow standard radiology operating procedures and will
report all incidental findings in their written report to be placed in the subject's
electronic medical record. The radiologist will also place recommendations for
follow-up. All abnormal findings will be brought to the attention of the ordering
provider, and will be reported to the Pl/AI. The PI/AI will then inform the subject of
the abnormalities found and will provide recommendations for follow-up. The Pl/ AI
will then send an encrypted e-mail to the subject's primary care provider with the
information about the abnormality.
o
Impact on Future Insurance: Subjects who separate from the military in a way that
does not permit the continuation of Tri Care benefits may have increased insurance
premiums and/or difficulty obtaining civilian insurance upon separation/retirement if
this study determines they have coronary artery disease, even if they are
asymptomatic. However, learning about a subject's atherosclerosis may lead to
treatment and life style changes that may reduce the risk of heart attack and other
cardiovascular events, thus decreasing the insurance costs long-term.
o
Possibility of Medical Board: There is the possibility that the cardiac CT scan could
discover a medical problem/condition that would require a medical evaluation board
to assess the ability of the enlisted member to continue duty in the military. Based on
the inclusion criteria, the likelihood of a subject in this study ending up medically
boarded from service is very slight.
o
Impact on TriCareN eterans Affairs (VA): This study could potentially identify
individuals as having coronary artery disease who were not formerly recognized as
having this diagnosis. This could lead to subjects starting new medications that
would need to be covered by their insurance following separation/retirement. This
could also lead to establishment of the fact that the subject's coronary artery disease
developed while on active duty and could have significant impact on the VA system
and disability claims at time of retirement. However, learning about a subject's
atherosclerosis may lead to treatment/life style changes that may decrease the
cost/impact on the TriCareN A system in the future.
o
Risks of blood draw: infection, bleeding, discomfort, bruising
o
Risks of collecting protected health information: potential loss of privacy and/or
confidentiality
•
Benefits:
o
Benefits to the Subject:
•
Earlier detection of coronary artery disease.
•
More accurate/personalized assessment of cardiovascular risk.
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For Protocol Office use only: 
Protocol title: Assessment of Coronary Artery Calcium in Active Duty 
Enlisted Military Members with 10 or More Years of Service 
FDG20130024H Protocol v15 w Amend 9 
name redacted 6Feb20 
DGMC Human Research Protocol 
•
One-on-one counseling to discuss results and risk factor modification in order
to motivate the subje,ct and potentially improve outcomes for subjects with
CAC>O.
•
For subjects with CAC score of zero, a letter informing them of their result
and encouraging them to continue making healthy lifestyle choices may
reinforce the subject's positive behaviors.
•
Benefits Outweigh the Risks: This study will provide subjects with their Coronary Artery
Calcium score. This score helps establish a ·risk score that indicates a more
personalized/individualized likelihood of a cardiovascular event in the future. By informing
the subject of their risk score and having a results letter sent or counseling session reviewing
their results, they are able to better understand what interventions/lifestyle modifications can
be completed to potentially decrease their risk of a cardiovascular event in the future. This
study can also provide the military with information about the prevalence of atherosclerosis
in enlisted members with 10 or more years of service, which could assist public health and
the military in making policies/influencing the military culture to promote healthy changes
that decrease the risk of atherosclerosis.
6.9. Safeguards for Protecting Subjects: 
•
This study involves greater than minimal risk to subjects as it involves the exposure to
radiation during a CT scan. Primary monitoring of the study will be performed by the
study team, who will review accrual and any adverse events on a real-time basis. The
study team will ensure that all eligibility criteria and consent requirements are met prior
to a subject's participation in the study and that all study procedures and adverse event
reporting occur according to the IRB approved protocol. Potential adverse events and
risk factors for this study are specifically listed in section 6.8 within this protocol and will
be discussed with subjects prior to enrollment. Any event will be graded by severity and
outcome. Study staff will make certain that all adverse events are recorded and reported
according to AFI 40-402 and SGSE Operating Instruction 40-402-0 I. Cumulative
adverse events will be reviewed monthly. The study team with the advisement of the
medical monitor and IRB will make decisions regarding cessation of accrual, and
whether or not to close the study on the basis of frequency or severity of Unanticipated
Problems Involving Risk to Subject or Others (UPIRS0s), and/or Serious Adverse Events
(SAEs). Any deviation, cessation in accrual or early study close will be communicated to
the IRB immediately.
•
All subjects will be treated in compliance with AFI 40-402 and applicable FDA and
DHHS guidelines.
•
All study staff members wilt be informed by direct personal communication about any
UPIRSOs or SAEs. If any protocol changes are needed, the PI will submit a modification
request to the IRB. Protocol changes will not be implemented prior to IRB approval
unless necessary to eliminate apparent immediate hazards to the research subjects. In
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For Protocol Office use only: 
Protocol title: Assessment of Coronary Artery Calcium in Active Duty 
Enlisted Military Members with 10 or More Years of Service 
FDG20130024H Protocol v15 w Amend 9 
name redacted 6Feb20 
DGMC Human Research Protocol 
such a case, the IRB will be promptly informed of the change following implementation 
(within 5 working days). 
•
Standard measures for protection of subject privacy and confidentiality that are currently
being practiced will continue. All electronic data will be housed on a Common Access
Card enabled computer accessible only to study personnel within a secured office. All
electronic transmissions of data will be encrypted over a secured network. All hard copy
records will be stored in a locked file cabinet in a secure room for the duration of the
study. Upon the close of the study all records will be transferred to the CIF for storage
for three years then moved to base storage IAW DODI 3216.02.
•
All subjects enrolled in the study will be provided with a phone number to contact during
business hours if they are experiencing any concerning symptoms. All enrollees are DoD
beneficiaries and can therefore seek treatment at DGMC any time they or the research
team are concerned about a change in their health. The emergency room at DGMC is
available 24 hours per day, seven days a week.
•
Privacy: All subject interviews will be conducted in a private office, behind a closed
door. Any phone calls to subjects for appointment reminders or any other reason will be
conducted in an office behind closed doors.
•
Protecting Collected Information: During data collection, subject identifiers will be
present on the data to ensure accuracy. Protected Health Information will be restricted to
the PI, AI, research coordinators and the statisticians who all have been HIP AA trained.
All paper documentation will be stored in locked files and all electronic materials will be
stored in password-protected electronic databases. Once all data have been collected,
subject identifiers will be removed by the Pl/Al. PHI will be shared with the subject's
primary care provider if abnormal lab results, abnormal CAC score, or incidental findings
on chest CT are discovered. Other than the primary care provider if necessary, PHI will
not be shared with anyone outside the study team.
•
Risk Modification:
o
Exposure to Radiation: The radiation exposure risk is equivalent to 24 chest x-rays,
and is approximately ^ of the background radiation the subject would be exposed to
in a year. While the· radiation dose cannot be decreased, the CT protocol is designed
to run the scan with as few slices/as little radiation exposure as is necessary to obtain
the required images. All females who may be pregnant or are pregnant at the time of
expressing interest in participation will be excluded from this study.
o
Emotional Response to/Stress Due to Results: Some subjects may have results that
indicate a high risk of a cardiovascular event in the future. This news could be
emotionally stressful to the individual. Subjects will be provided with the study
coordinator's phone number which they can call during business hours if they are
feeling overwhelmed by the results of their test. The DGMC ER is also available 24
Form Revised as of25 July 2012 
60MDG\SGSE\IRB Folder\lRB\Templates and Forms\Human 
Page 23 of29 

For Protocol Office use only: 
Protocol title: Assessment of Coronary Artery Calcium in Active Duty 
Enlisted Military Members with 10 or More Years of Service 
FDG20130024H Protocol vl5 w Amend 9 
name redacted 6Feb20 
DGMC Human Research Protocol 
hours a day. The study coordinator will offer information about mental health 
services available at Travis Air Force Base if requested. 
o
Impact on Future Insurance: Subjects who later separate from the military may not
continue to receive TriCare benefits and may have increased civilian insurance
premiums and/or difficulty obtaining civilian insurance if this study determines they
have coronary artery disease, even if they are asymptomatic. There is no way to
decrease this risk, but subjects can opt to not participate in this study if they are
concerned about impact on future insurance.
o
Risks of blood draw: Infection, bleeding, discomfort, bruising. These risks are
decreased by using sterile needles, cleaning the skin prior to blood draw and pressure
applied after withdrawing the needle.
•
PCM Notification: Primary care physicians will be notified of all CAC scores >O via an
encrypted e-mail that includes follow-up recommendations (See attached PCM
Notification E-Mail Template). A telephone consult note will also be entered in AHLTA
with CAC score results. Any abnormal HgbA 1 C or lipid panel labs will be brought to the
attention of the PCM via encrypted e-mail.
•
Data Monitoring: Data will be monitored monthly by the PI.and study staff to identify
any adverse events, and to ensure all subjects who underwent cardiac CT scan and CAC
scoring attended all recommended follow-up, to include a results letter, follow-up in
metabolic clinic, OR follow up in cardiology.
•
Stop Rules: No stop rules are anticipated. As this is an observational study looking partly
at prevalence of atherosclerosis in enlisted military members with 10 or more years of
service, the study team does not anticipate stopping the study early. However if interim
statistical analysis shows a prevalence of atherosclerosis = 0, then the principle investigator
may stop the study.
7. Conflict of Interest
No conflicts of interest have been identified by any of the research team members.
8. Collaborative Efforts
No collaboration with other facilities will be pursued at this time.
9. Investigation Schedule
Mar-
May 
Apr 
2013-
2013 
Nov 
2013 
IRB Aooroval 
X 
X 
Surgeon General Approval 
X 
Form Revised as of25 July 2012 
Nov 
Nov 
Nov 
Nov 
Dec 
Dec 
2013-
2013-
2013-
2013-
2016 
2016-
Nov 
Nov 
Nov 
Dec 
Mar 
2016 
2016 
2016 
2016 
2017 
X 
60MDG\SGSE\IRB Folder\IRB\Templates and Forms\Human 
Page 24 of29 

For Protocol Office use only: 
PIname redacted 6Feb20 
Protocol title: Assessment of Coronary Artery Calcium in Active Duty 
Enlisted Military Members with 10 or More Years of Service 
FDG20130024H Protocol v15 w Amend 9 
DGMC Human Research Protocol 
Recruitment 
X 
X 
Enrollment 
X 
X 
X 
Baseline Data 
X 
X 
X 
Testing 
X 
X 
X 
Data Collection 
X 
X 
X 
Statistical Analysis 
X 
Publications/Reports 
Estimated Date of Investigation Beginning: 01 August 2013 
Estimated Date of Completion: 30 December 2016 
X 
X 
X 
10. Use of Investigational Drug(s) 
S No 
D Yes 
No investigational drugs will be used in this investigation. 
11. Use of lnvestigational Device(s) 
S No 
D Yes 
No investigational devices will be used in this investigation. 
12. Support Required
Lab Support: 
X 
X 
R 
CLIA 
equest 
cert1 1cates fr om a 11 non-DGMC l b 
fil 
a oratones or your 1 es. 
X 
. 
Test Name 
Standard Care? 
Which lab will perform each test? 
Suooort letter attached? 
HgbAlC 
Yes and No 
DGMC 
Yes 
Lipid Panel 
Yes and No 
DGMC 
Yes 
** Note: Some of these labs will be standard of care if the subject is diabetic and/or has 
hyperlipidemia and has not had labs drawn in the past 3 months. Those without these diagnoses 
will have these labs drawn for research purposes only. 
See attachment 16- Letter of Support- DGMC Lab 
Radioactive Materials or Radiology Support: 
If radioisoto es or radiation- roducin e ui ment will be used, describe here. 
Cardiac CT 
No 
DGMC 
Yes 
See attachment 17 - Letter of Support - Radiology 
* Any Radiation exposure that is not standard care requires Radiation Safety Committee review.
See attachment 18 - Radiation Safety Committee Approval
Nursing/Technician Support: 
NIA 
CIF Support: 
Describe what you will be asking the CIF staff to do in support of your research or specialized 
lab equipment you will need to carry out your proposal (bio-statistician consultation, research 
support staff/coordinator, lab technician support, etc.). 
Form Revised as of25 July 2012 
60MDG\SGSE\IR8 Folder\lRB\Templates and Forms\Human 
Page 25 of29 

For Protocol Office use only: 
Protocol title: Assessment of Coronary Artery Calcium in Active Duty 
Enlisted Military Members with 10 or More Years of Service 
FDG20130024H Protocol vlS w Amend 9 
Task 
Personnel 
Time and Frequency 
needed 
name redacted 6Feb20 
DGMC Human Research Protocol 
Support letter attached? 
Biostatistics 
name 
redacted 
6Feb20 
-4 hours, once at end of data
Yes 
Consultation 
collection
Study Coordinator 
0.1 FTEs or less
Study Coordinator 
0.1 FTEs or less 
Yes 
Yes 
See attachment 19 - Letter of Support - CIF 
Other Support: 
Heart Lung and Vascular Center - follow-up appointments for subjects will be required with the 
metabolic clinic or the cardiology clinic. (See attachment 20 - Letter of Support- HL&VC). 
13. Budget, Equipment, and Supplies
NIA
14 M 
. anpower 
Rank 
AFSC/Job Title 
Lt Col 
Staff 
Capt 
Resident 
Study Coordinator 
Contractor 
Study Coordinator 
Contractor 
Clinical Research 
Contractor 
Nurse 
Research Assistant 
Contractor 
Research Assistant 
Contractor 
Clinical Pharmacist 
Contractor 
15. Authorized Institutional Official (AIO)
(name/contact info redacted 6Feb20),
16. Bibliography
# hours duty time 
# hours off-duty time 
50 
50 
180 
100 
185 
0 
185 
0 
10 
0 
10 
0 
10 
0 
40 
0 
1. National Center for Health Statistics. Health, United States, 2008 with Chartbook on
Trends in the Health of Americans. http://www.cdc.gov/nchs/hus/updatedtables.htm.
2009.
2. Executive Summary of The Third Report of The National Cholesterol Education Program
(NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood
Cholesterol In Adults (Adult Treatment Panel III). Jama. 2001 May 16;285(19):2486-97.
Form Revised as of25 July 2012 
60MDG\SGSE\IRB Folder\IRB\Templates and Forms\Human 
Page 26 of29 

For Protocol Office use only: 
Protocol title: Assessment of Coronary Artery Calcium in Active Duty 
Enlisted Military Members with IO or More Years of Service 
FDG20130024H Protocol v15 w Amend 9 
name redacted 6Feb20 
DGMC Human Research Protocol 
3. Akosah KO, Schaper A, Cogbill C, Schoenfeld P. Preventing myocardial infarction in the
young adult in the first place: how do the National Cholesterol Education Panel III
guidelines perform? J Am Coll Cardiol. 2003 May 7;41(9):1475-9.
4. Wilson PWF, D'Agostino RB, Levy D, et al. Prediction of coronary heart disease using
risk factor categories. Circulation. 1998;97; 183 7-184 7.
5. Ridker PM, Paynter NP, Rifai N, Gaziano JM, Cook NR. C-reactive protein and parental
history improve global cardiovascular risk prediction: the Reynolds Risk Score for men.
Circulation. 2008 Nov 25; 118(22):2243-51, 4p following 51.
6. Budoff MJ, Achenbach S, Blumenthal RS, Carr JJ, Goldin JG, Greenland P, et al.
Assessment of coronary artery disease by cardiac computed tomography: a scientific
statement from the American Heart Association Committee on Cardiovascular Imaging
and Intervention, Council on Cardiovascular Radiology and Intervention, and Committee
on Cardiac Imaging, Council on Clinical Cardiology. Circulation. 2006 Oct
17;114(16):1761-91.
7. Raggi P, Cooil B, Shaw LJ, Aboulhson J, Takasu J, Budoff M, et al. Progression of
coronary calcium on serial electron beam tomographic scanning is greater in patients with
future myocardial infarction. Am J Cardiol. 2003 Oct 1 ;92(7):827-9.
8. Anand DV, Lim E, Hopkins D, Corder R, Shaw LJ, Sharp P, et al. Risk stratification in
uncomplicated type 2 diabetes: prospective evaluation of the combined use of coronary
artery calcium imaging and selective myocardial perfusion scintigraphy. Eur Heart J.
2006 Mar;27(6):713-21.
9. http://www.radiologyinfo.org/en/info.cfm?PG=ct_calscoring
10. Naghavi M, Falk E, Hecht HS, Jamieson MJ, Kaul S, Berman D, et al. From vulnerable
plaque to vulnerable patient--Part III: Executive summary of the Screening for Heart
Attack Prevention and Education (SHAPE) Task Force report. Am J Cardiol. 2006 Jul
17;98(2A):2H-15H.
11. Webber BJ, Seguin, PG, Burnett DG, Clark LL, Otto, JL. Prevalence of and Risk
Factorsfor Autopsy-Determined Atherosclerosis Among US Service Members, 2001-
2011. Jama. 2012 Dec 26; 308(24):2577-2583.
12. Bray, R.M., Pemberton, M.R., Hourani, L.L., et al., 2008 Department of Defense Survey
of Health Related Behaviors among Active Duty Military Personnel. 2009 September.
Research Triangle Park, NC: Research Triangle Institute.
13. Nolte R, Franckowiak SC, Crespo CJ, Andersen RE. U.S. military weight standards: what
percentage of U.S. young adults meet the current standards?Am J Med. 2002 Oct
15; 113(6):486-90.
14. Army Medical Surveillance Activity. Body Mass Index (BMI) among 18-year old
Civilian Applicants for U.S. Military Service 1996-2005. Medical Surveillance Monthly
Report (MSMR); 2006 Dec; 12(9):2-6.
15. Armed Forces Health Surveillance Center. Diagnoses of Overweight/Obesity, Active
Component, U.S. Armed Forces, 1998-2008. Medical Surveillance Monthly Report
(MSMR); 2009 Jan; 16(01 ): 2-7
16. http://www.mreinfo.com
Form Revised as of25 July 2012 
60MDG\SGSE\IR8 Folder\IRB\Templates and Forms\Human 
Page 27 of29 

For Protocol Office use only: 
Protocol title: Assessment of Coronary Artery Calcium in Active Duty 
Enlisted Military Members with IO or More Years of Service 
FDG20130024H Protocol v15 w Amend 9 
name redacted 6Feb20 
DGMC Human Research Protocol 
17. Levy D. Combating the Epidemic of Heart Disease. Jama. 2012 Dec 26; 308(24):2624-
2625.
18. Taylor AJ, Feuerstein I, Wong, H, Barko, W, Brazaitis M, O'Malley PG. Do conventional
risk factors predict subclinical coronary artery disease? Results from the Prospective
Army Coronary Calcium Project. Am Heart J. 2001 Mar; 141 (3):463-8.
19. Yeboah J, McClelland RL, Polansky TS, Burke GL, Sibley CT, O'Leary D, Carr JJ, Goff
DC, Greenland P, Herrington DM. Comparison of novel risk markers for improvement in
cardiovascular risk assessment in intermediate-risk individuals. Journal of the American
Medical Association. 2012 Aug; 308 (8):788-795.
17. Attachments
1. Diagnostic Criteria for Metabolic Syndrome
2. HIP AA Authorization
3. Initial Interview/Questionnaire
4. Inclusion/Exclusion Criteria Checklist
5. Informed Consent Document
6. Subject Handout on Cardiac CT
7. Results Letter
8. Telephone Consult Template for AHTLA Notes
9. PCM Notification E-Mail Template
10. Framingham Risk Calculation Tables
11. Recruitment Flier- Landscape
12. Recruitment Flier - Portrait
13. Recruitment Trifold Pamphlet
14. Recruitment Research Announcement
15. Recruitment Script for TAP Course
16. Letter of Support - Lab
17. Letter of Support - Radiology
18. Radiation Safety Committee Approval
19. Letter of Support - CIF
20. Letter of Support - Heart Lung & Vascular Center
21. Adverse Event Log
22. Certificate of Compliance
23. Curriculum Vitae for Each Study Team Member and Medical Monitor
24. Human Protections Training Certificates for Each Study Team Member
25. IIAs for non-staff
26. HIPAA Waiver
27. Screening/Phone Script
Form Revised as of25 July 2012 
60MDG\SGSE\IRB Folder\IRB\Templates and Forms\Human 
Page 28 of29 

You Could Have Heart 
Disease Without Knowing It 
The CAC Research Study is Looking 
at Your 10 Vear Risk of Heart Attack 
or Stroke Using a CT Scan 
You May Be Eligible If You: 
•
Are Active Duty ENLISTED Military with
>10 Years of Service
•
Are a Male 435 Years Old OR a Female
4 45 Years Old
•
Have at Least One Risk Factor for Heart
Disease
For More Information Call: 
name/contact info redacted 
6Feb20

· 
0 
b You Could Have Heart 
0 Disease Without Knowing It 
qz: The CAC Research Study is Looking at Your 10 Year Risk of
Heart Attack or Stroke Using a CT Scan 
You May Be Eligible If You: 
•
Are Active Duty ENLISTED Military with >10 years of Service
•
Are a Male +35 Years Old OR a Female + 45 Years Old
•
Have at Least One Risk Factor for Heart Disease
For More Information Call: 
(Name/contact info redacted 6 Feb 20) 
------
___________, 
WU	W
kJkl 

For Protocol Office use only: 
Protocol title: Assessment of Coronary Artery Calcium in Active Duty 
Enlisted Military Members with 10 or More Years of Service 
FDG20130024H Protocol v14 w Amend 8 
name redacted 6Feb20 
DGMC Human Research Protocol 
18. Commander's Acknowledgment of Review and Approval
Principal Investigator: I am aware that I am not authorized to accept any funds or other form 
of compensation for conducting research. All subjects will be treated in compliance with 
applicable Air Force, DoD and federal regulations, as well as applicable FDA and DHHS 
guidelines. I have read, understand, and signed the attached Certificate of Compliance. I 
understand I must complete a review of this protocol at least mvery 12 months to prevent 
expiration of the study' s approval. I will notify the protocol office prior to relocations, 
separation actions, or closure. 
D Initial Submission 
(ALL signatures required) 
signature/name 
redacted 6 Feb 20
Form Revised as of25 July 2012 
n Amendment Submission 
(PI signature ONLY) 
60MDG\SGSE\IRB Folder\IRB\Templates and Fonns\Human 
Page 29 of29