SUPPLEMENTARY MATERIALS
Image Analysis of Arterial Inflammation
Measurements were made in the axial plane and SUVmax was recorded for each region
of interest (ROI). Arterial target-to-background ratio (TBR) was defined as the ratio of
the mean of the SUVmax measurements along the full length of the artery to the
background venous activity derived from either the superior vena cava (for correction of
aortic values), or the internal jugular veins (for correction of carotid values). Standardized
uptake value (SUVmax) was calculated as a time- and dose-corrected tissue radioactivity
divided by body weight. The background SUV was obtained by placing a volume of
interest in the venous structure as previously done (1,2). To evaluate FDG uptake in
control tissues, volumes of interest (VOIs) were placed in subcutaneous adipose tissue
(SAT) and SUVs were recorded. Additionally, pectoralis muscle FDG uptake was
measured in the ACS Study (study 1). Identification of SAT was guided by CT, as
described in prior studies.(3)
Adjudication of CVD Events
Patients were categorized as having ACS (ST-elevation MI or non-ST elevation MI or
unstable angina) or new-onset stable angina based on the nature and duration of chest
pain, medical history, and available diagnostics such as ECG and/or biomarkers, and as
supported by findings on coronary arteriography. TIA was defined as the presence of
focal neurological symptoms or signs lasting < 24 hours without signs of acute infarction
on imaging vs. ischemic stroke, characterized by focal neurologic symptoms in the
distribution of symptomatic carotid artery lasting >24 with no apparent cause other than a
vascular one and supported by findings on imaging such as CT. PAD was based on signs
and symptoms (such as intermittent claudication, rest pain, ulcers, or gangrene) and noninvasive evaluation based on hemodynamic measures. Heart failure was defined based on
signs and symptoms (such as dyspnea or fatigue or edema), medical history and
diagnostics (such as ECG, chest radiograph, or two-dimensional echocardiography with
Doppler). CVD death was defined as sudden death due to cardiovascular causes.
Gene expression assays
Phlebotomy was performed at the time of PET/CT imaging and total RNA was isolated
from frozen PAXgene blood tubes (Qiagen, Inc.) by Asuragen, Inc., according to the
company’s standard operating procedure for manual isolations. The integrity of total
RNA was qualified by microfluidic electrophoresis, using the Agilent Bioanalyzer Nano
Assay and the Caliper LabChip system. Samples for quantitative RT-PCR (qRT-PCR)
analysis by the custom Life Technologies TaqMan® Array Card (TA) were processed
according to the company’s standard operating procedures. All amplifications were
performed on a validated Life Technologies Applied Biosystems 7900HT real-time
thermocycler equipped with the TA upgrade components. Automatic baseline and
threshold of 0.1 was used for all assays and all arrays run. Mean Ct values were recorded
and calculated by Life Technologies’ SDS v3.2 software and summarized in Excel
spreadsheets. Count values greater than 36.68 were flagged because they fell within 10fold level of the final cycle and were deemed less reliable or not expressed. qRT-PCR
counts were normalized using mRNA levels of the housekeeping TATA Binding Protein.
Supplemental Figure 1: Measurement of Splenic Metabolic Activity
Splenic FDG uptake was assessed by manually drawing a region of interest (ROI) (shown
as the red circle) in axial (A), sagittal (B) and coronal (C) planes. SUVmax was recorded
in each ROI, and average splenic activity was calculated as mean of SUVmax values of
the 3 ROIs.
Abbreviations: FDG, 18F-flurodeoxyglucose; SUV, Standardized Uptake Value; TBR,
target-to-background ratio.
Supplemental Figure 1.
Supplemental Table 1. Summary of ACS Patient Presentations
Age
Gender
(yrs)
ACS
Classification
38
F
UAP
60
M
NSTEMI
43
M
UAP
51
F
NSTEMI
65
M
NSTEMI
53
M
UAP
59
F
NSTEMI
62
M
NSTEMI
69
M
NSTEMI
63
M
UAP
56
F
STEMI
57
F
UAP
61
M
UAP
66
M
UAP
63
F
UAP
Clinical Presentation
Accelerating, severe, exertional typical CP
radiating to left arm, alleviated by rest.
Accelerating, typical SSCP relieved with rest and
nitroglycerin
Intermittent, progressive CP associated with SOB,
diaphoresis and left arm tingling
Progressive, exertional CP and SOB, relieved by
rest
New-onset, squeezing SSCP radiating to left arm,
exertional, and relieved
Progressive, exertional CP with minimal exertion,
relieved by rest
Acute SSCP/tightness radiating to bilateral arms,
alleviated with rest
Acute-onset, severe SSCP with minimal exertion,
relieved by rest
Sudden-onset, left arm numbness and CP
associated with diaphoresis
Progressive, exertional typical CP radiating to
throat over 4 days
Acute-onset, typical SSCP at rest
Accelerating, exertional CP associated with
dyspnea, and relieved by rest
Progressive, left-sided CP associated with
dyspnea, and relieved by rest
Acute-onset, exertional jaw pain radiating to
throat and shoulders, alleviated with rest
Accelerating, exertional CP over 3 weeks
associated with nausea, relieved by rest.
EKG
Changes
Troponin
Coronary Anatomy
Stent
Negative
90% prox RCA
Yes
0.41
95% RCA
Yes
Negative
90% PDA, 60% D2
Yes
0.23
90% mid LAD
Yes
0.38
80% RCA
Yes
Normal
Negative
99% prox RCA
Yes
T-wave
inversions
6.14
70% prox LAD, 60% LAD
Yes
Normal
0.62
95% prox LAD
Yes
STdepressions
3.4
80% D1, 50% LAD
Yes
Normal
Negative
85% LAD, 40% RCA
Yes
ST-elevation
>8
100% mid LCx, 80% RCA
Yes
T-wave
inversions
Negative
95% RCA, 70% LCx,
Yes
Normal
Negative
80% ostial LAD, 60%
LAD
Yes
Negative
90% RCA, 60% LCx
Yes
Negative
85% LAD, 45% LCx
Yes
T-wave
inversions
T-wave
inversions
Normal
T-wave
inversions
STdepressions
T-wave
inversions
T-wave
inversions
69
M
NSTEMI
64
M
UAP
54
M
STEMI
67
M
NSTEMI
61
M
NSTEMI
56
M
NSTEMI
45
M
STEMI
Acute-onset, severe CP radiating to shoulder and
jaw
Acute-onset, SSCP at rest radiating to left arm and
neck associated with face numbness and tingling
Sudden-onset, SSCP associated with nausea and
left arm numbness
Progressive SSCP associated with SOB, neck
pain, and left arm tingling
Acute CP radiating to both arms, relieved with
rest
Intermittent exertional chest pressure over 2
weeks associated with dyspnea
Acute typical CP awakened from sleep, worse
with exertion and relieved by rest
ST-depression
27
90% LAD
Yes
T-wave
inversions
Negative
90% LAD, 70% LCx
Yes
ST-elevation
Negative
100% prox LAD, 40%
RCA
Yes
ST-depression
0.2
90% LCx, 40% LM
Yes
ST-depression
0.64
85% RCA
Yes
T-wave
inversion
0.26
90% OM1
Yes
ST-elevation
Negative
100% prox LAD
Yes
Abbreviations: CP, chest pain; D, diagonal; ECG, electrocardiogram; LAD, left anterior descending artery, LCx, left circumflex artery; LM, left main;
mid, middle; NSTEMI, non-ST elevation myocardial infarction, OM, obtuse marginal; PDA, posterior descending artery; prox, proximal; RCA, right
coronary artery; SSCP, substernal chest pain; STEMI, ST elevation myocardial infarction, UAP, unstable angina pectoris
5
Supplemental Table 2. Baseline cancer and cancer treatment status of “Clinical Outcomes”
subjects
Full Cohort (n=464)
Individuals Without
Subsequent CVD
(n=430)
Individuals With
Subsequent CVD
(n=34)
p-value
Prior history of cancer
None
Lymphoma
Hemotologic
Lung
Gastrointestinal
Breast
Head and Neck
Skin
Multiple
Other
68 (15)
184 (40)
1 (<1)
15 (3)
43 (9)
71 (15)
36 (8)
20 (4)
22 (5)
4 (<1)
57 (13)
177 (41)
1 (<1)
11 (3)
39 (9)
69 (16)
35 (8)
18 (4)
19 (4)
4 (<1)
11 (32)
7 (21)
0 (0)
4 (12)
4 (12)
2 (6)
1 (3)
2 (6)
3 (9)
0 (0)
0.005
0.01
0.92
0.02
0.38
0.08
0.23
0.44
0.23
0.74
None
Chemotherapy
Radiotherapy
Chemoradiotherapy
103 (22)
127 (27)
32 (7)
197 (42)
87 (20)
124 (29)
31 (7)
183 (42)
16 (47)
3 (9)
1 (3)
14 (41)
0.001
0.006
0.29
0.51
Radiation To Chest
Immunotherapy (IL2, interferon, G-CSF)
84 (18)
76 (17)
8 (23)
0.26
5 (1)
5 (1)
0 (0)
0.68
Values are presented as n (%).
Abbreviations: IL-2, interleukin 2; G-CSF, granulocyte colony stimulating factor
6
References
1.
2.
3.
Tawakol A, Fayad ZA, Mogg R, et al. Intensification of statin therapy results in a
rapid reduction in atherosclerotic inflammation: results of a multicenter
fluorodeoxyglucose-positron emission tomography/computed tomography
feasibility study. J Am Coll Cardiol 2013;62:909-17.
Subramanian S, Tawakol A, Burdo TH, et al. Arterial inflammation in patients
with HIV. JAMA 2012;308:379-86.
Rosenquist KJ, Pedley A, Massaro JM, et al. Visceral and subcutaneous fat
quality and cardiometabolic risk. JACC Cardiovasc Imaging 2013;6:762-71.