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Online Appendix for the following JACC: Cardiovascular Imaging article
TITLE: Coronary Vascular Dysfunction and Prognosis in Patients With Chronic
Kidney Disease
AUTHORS: Venkatesh L. Murthy, MD, PHD, Masanao Naya, MD, PHD, Courtney R.
Foster, BS, Jon Hainer, BS, Mariya Gaber, ALM, Sharmila Dorbala, MD, MPH, David M.
Charytan, MD, MSC, Ron Blankstein, MD, Marcelo F. Di Carli, MD
APPENDIX
Online Supplement
Table 1. Baseline Characteristics by CFR
Variable
Demographics
Age (y)
Male Gender
Hispanic
Race
White
Black
Other/Unknown
Risk Factors
BMI (kg/m2)
BMI ≥ 30 kg/m2
Hypertension
Dyslipidemia
Diabetes
Family history of CAD
Tobacco Use
Duke Clinical Risk (%)
Renal Function
CKD Stage 3
CKD Stage 4
CKD Stage 5
Dialysis
eGFR MDRD (ml/min/1.73 m2)
Medications
Aspirin
β-adrenergic Blockers
CFR <1.5
(n=439)
CFR ≥1.5
(n=427)
All Patients
(n=866)
P-Value
72.4 [62.7-80.4]
227 (51.7)
30 (6.8)
69 [59.6-78.6]
208 (48.7)
49 (11.5)
71.1 [61.3-79.8]
435 (50.2)
79 (9.1)
0.001
0.41
0.02
389 (65.8)
68 (15.5)
82 (18.7)
252 (59.0)
81 (19.0)
94 (22.0)
541 (62.5)
149 (17.2)
176 (20.3)
0.12
27.8 [24.1-32.4]
169 (38.5)
406 (92.5)
321 (73.1)
223 (50.8)
97 (22.1)
36 (8.2)
0.7 [0.4-0.9]
28.5 [24.8-33.5]
178 (41.7)
384 (89.9)
285 (66.7)
165 (38.6)
92 (21.5)
39 (9.1)
0.5 [0.2-0.9]
28.2 [24.4-33]
347 (40.1)
790 (91.2)
606 (70)
388 (44.8)
189 (21.8)
75 (8.7)
0.6 [0.3-0.9]
0.13
0.37
0.19
0.05
0.0004
0.87
0.63
<0.0001
264 (60.1)
67 (15.3)
108 (24.6)
84 (19.1)
37.2 [15.5-49]
295 (69.1)
39 (9.1)
93 (21.8)
69 (16.2)
44.4 [20.4-54.2]
559 (64.6)
106 (12.2)
201 (23.2)
153 (17.7)
40.7 [17.3-51.8]
0.007
0.28
<0.0001
295 (67.2)
345 (78.6)
258 (60.4)
298 (69.8)
553 (63.9)
643 (74.2)
0.04
0.003
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Cholesterol agents
323 (73.6)
286 (67)
609 (70.3)
0.04
Insulin
111 (25.3)
83 (19.4)
194 (22.4)
0.04
Oral hypoglycemic agents
37 (8.4)
36 (8.4)
73 (8.4)
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Ca-channel blockers
133 (30.3)
136 (31.9)
269 (31.1)
0.66
ACE inhibitors
174 (39.6)
187 (43.8)
361 (41.7)
0.22
Nitrates
88 (20)
56 (13.1)
144 (16.6)
0.006
Diuretics
216 (49.2)
203 (47.5)
419 (48.4)
0.63
Indications
Chest Pain
124 (28.2)
170 (39.8)
294 (33.9)
0.0003
Dyspnea
143 (32.6)
140 (32.8)
283 (32.7)
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Cardiomyopathy
4 (0.9)
1 (0.2)
5 (0.6)
0.37
Post-MI
93 (21.2)
38 (8.9)
131 (15.1)
<0.0001
Pre-operative
77 (17.5)
52 (12.2)
129 (14.9)
0.03
Cardiovascular History
Any prior CAD
288 (65.6)
187 (43.8)
475 (54.8)
<0.0001
Recent MI (≤30 days)
116 (26.4)
48 (11.2)
164 (18.9)
<0.0001
Remote MI (>30 days)
111 (25.3)
85 (19.9)
196 (22.6)
0.06
Prior PCI
121 (27.6)
94 (22)
215 (24.8)
0.06
Prior CABG
103 (23.5)
57 (13.3)
160 (18.5)
0.0002
Cerebrovascular disease
52 (11.8)
17 (4)
69 (8)
<0.0001
Peripheral vascular disease
54 (12.3)
25 (5.9)
79 (9.1)
0.001
Early revascularization (≤90 days
69 (15.7)
19 (4.4)
88 (10.2)
<0.0001
post-PET)
Imaging Parameters
Rest LVEF
51 [35-60]
56 [47-66]
54 [41-63]
<0.0001
LVEF reserve
278 (63.3)
348 (81.5)
626 (72.3)
<0.0001
Ischemia + scar (%)
8.8 [0-23.5]
0 [0-8.8]
4.4 [0-16.2]
<0.0001
Ischemia (%)
2.9 [0-10.3]
0 [0-4.4]
0 [0-7.4]
<0.0001
Global CFR
1.18 [1-1.34]
1.92 [1.68-2.29]
1.49 [1.18-1.92]
<0.0001
Stress Global MBF (ml/g/min)
1.18 [0.91-1.65]
1.98 [1.45-2.68]
1.55 [1.08-2.18]
<0.0001
Rest Global MBF (ml/g/min)
1.04 [0.8-1.36]
0.96 [0.75-1.28]
1 [0.79-1.32]
0.002
Continuous variables are presented as median (inter-quartile range). Dichotomous variables are presented as
number (%). Patients whose LVEF at stress was greater than that at rest were considered to have positive stressinduced increase in LVEF. BMI = body mass index. ACE = angiotensin converting enzyme. MI = myocardial
infarction. CAD = coronary artery disease. CKD = Chronic Kidney Disease. eGFR MDRD = estimated
glomerular filtration rate by modification of diet in renal disease formula. PCI = percutaneous coronary
intervention. CABG = coronary artery bypass graft. LVEF = left ventricular ejection fraction. CFR = coronary
flow reserve. MBF = myocardial blood flow.
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Table 2. Causes of Death
Cause of Death
All Patients
CFR <1.5
CFR ≥1.5
p-Value
(n=866)
Cardiac
88 (10.2%)
66 (15.0%)
22 (5.2%)
<0.0001
Non-Cardiac
67 (7.7%)
43 (9.8%)
24 (5.6%)
0.02
Vascular
2 (0.2%)
2 (0.5%)
0
0.50
Non-hemorrhagic stroke
7 (0.8%)
5 (1.1%)
2 (0.5%)
0.45
Other
51 (5.9%)
32 (7.3%)
20 (4.7%)
0.12
Unknown
6 (0.7%)
4 (0.9%)
2 (0.5%)
0.69
Any Cause
155 (17.9%)
109 (24.8%)
46 (10.8%)
<0.0001
Patients were divided at the median value of CFR corresponding to <1.5 and ≥1.5. CFR = coronary flow
reserve.
Table 3. Risk Reclassification
Model without CFR
Model with CFR
<2% Annual Risk
2-4% Annual Risk
>4% Annual Risk
Total
<2% Annual Risk
0 (0)
2.2 (100)
0 (0)
2.2
2-4% Annual Risk
0 (0)
10.1 (61.1)
6.5 (38.9)
16.6
>4% Annual Risk
0 (0)
0 (0)
84.7 (100)
84.7
0
12.4
91.1
103.5
<2% Annual Risk
170 (86.8)
25.8 (13.2)
0 (0)
195.8
2-4% Annual Risk
55 (22.6)
155.9 (64.0)
32.5 (13.4)
243.4
>4% Annual Risk
3 (1.3)
44 (13.6)
276.3 (85.5)
323.3
228
225.6
276.3
762.5
Patients with Cardiac Death
Total
Patients without Cardiac Death
Total
Reclassification table for censored data using method of Steyerberg and Pencina (1) from 2-year event data.
Parentheses indicate percentages of each pre-test category reclassified to each post-CFR category.
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Figure 1. Annualized Cardiac Mortality by Coronary Flow Reserve
Annualized cardiac mortality was computed across strata of coronary flow reserve (CFR) ranging from <1.0
(left) to ≥2.2 (right). Cardiac mortality rates were compared to the stratum containing patients with CFR ≥2.2
using Poisson regression and are indicated with asterisks where significant. The observed rates of cardiac
mortality suggest an inflection point in risk at approximately CFR=1.5.
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Figure 2. Univariate Predictors of Cardiac Death
Univariate predictors of cardiac mortality are shown. Hazard ratios are presented for a one unit increase except
for age (increase of 10 years), left ventricular ejection fraction (LVEF; decrease of 10%), extent of scar,
ischemia or both combined (increase of 10% of left ventricular mass). CAD indicates patient reported coronary
artery disease, known angiographic coronary stenosis, prior myocardial infarction or history of coronary
revascularization. Hx = history of. ASA = aspirin. BMI = body mass index.
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Figure 3. Annualized Cardiac Mortality By Coronary Flow Reserve and Duke
Clinical Score
In order to explore the incremental prognostic value of coronary flow reserve (CFR) beyond clinical measures
of cardiac risk, patients were characterized into tertiles of pre-test risk using the Duke Clinical Score (2) along
the horizontal axis. In each pre-test risk category patients were separated at the median value of CFR (i.e., 1.5).
In each category of pre-test risk, CFR separated groups with lower and higher annualized rates of cardiac
mortality, though significance, computed with Poisson regression, was achieved only among low and
intermediate pre-test risk groups.
References
1. Steyerberg EW, Pencina MJ. Reclassification Calculations for Persons With Incomplete Follow-up. Annals of
Internal Medicine 2010;152(3):195 –196.
2. Pryor DB, Shaw L, McCants CB, et al. Value of the History and Physical in Identifying Patients at Increased
Risk for Coronary Artery Disease. Annals of Internal Medicine 1993;118(2):81 –90.
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