Online Appendix for the following JACC article
TITLE: Multimarker Strategy for Short-Term Risk Assessment in Patients With Dyspnea in
the Emergency Department: The Multi mARKer Emergency Department (MARKED)-Risk
Score
AUTHORS:Luc W. Eurlings, MD, Sandra Sanders-van Wijk, MD, Roland van Kimmenade,
MD, PhD, Aart Osinski, MD, Lidwien van Helmond, MD, Maud Vallinga, MD, PhD, Harry
J. Crijns, MD, PhD, Marja P. van Dieijen-Visser, MD, PhD, Hans-Peter Brunner-La Rocca,
MD, PhD, Yigal M. Pinto, MD, PhD
APPENDIX
Supplemental table I: Assay performance characteristics
Marker
LOD
Interassay CV
Reference value
NT-proBNPa
5.1 μg/L(16)
6.8% at 74.4 μg/L(16)
99%: males 265 μg/L,
females 301 μg/L (16)
Hs-cTnTb
0.001 μg/L(18)
3.0% at 0.021 μg/L,
99%: 0.016 μg/L(18)
1.4% at 3.03 μg/L(18)
Hs-CRPc
0.175 mg/L(17)
3.7% at 0.25,
95%: 8.4 mg/L (17)
1.0% at 45 mg/L(17)
Cystatin-Cd
0.004 mg/L (20)
2.0% at 0.9 mg/L,
95%: 0.95 mg/L* (21)
2.2% at 1.8 mg/L (10)
Galectin-3e
1.13 μg/L (19)
10% at 6 μg/L,
95%: 20.3 μg/L (19)
7% at 21 μg/L,
15% at 70 μg/L (19)
a: measured by the electrochemiluminescence immunoassay using an Elecsys 2010 analyzer (Roche Diagnostics
GmbH, Mannheim, Germany)
b: measured by precommercial highly sensitive fifth generation cTnT assay (hs-cTnT) using an the Elecsys 2010
analyser (Roche Diagnostics GmbH, Mannheim,Germany)
c: measured by the CardioPhase hsCRP assay on the BN ProSpec (Siemens Healthcare Diagnostics Inc. New
York, United States)
d: measured by the N Latex Cystatin C assay on the BN ProSpec (Siemens Healthcare Diagnostics Inc. New
York, United States)
c: measured by the Galectin-3 electrochemiluminescence immunoassay (BG Medicine Inc., Waltham, MA, USA
United States) on the iMark™ Microplate Absorbance Reader (Bio-Rad Laboratories, Inc)
LOD = limit of detection; CV = coefficient of variation.
Supplemental table II: Performance of biomarkers for prediction of 90-day mortality
Marker
AUC (95% CI)
P
Cut-off
Sensitivity
Specificity
PPV
NPV
NT-proBNP
0.73 (0.67-0.78)
<0.001
4500 pg/ml
72%
64%
23%
94%
Hs-cTnT
0.74 (0.69-0.80)
<0.001
0.04 μg/L
74%
67%
25%
95%
Hs-CRP
0.73 (0.68-0.79)
<0.001
25 mg/L
67%
72%
26%
94%
Galectin-3
0.75 (0.69-0.81)
<0.001
25 μg/L
76%
64%
24%
95%
Cystatin-C
0.73 (0.68-0.78)
<0.001
1.125 mg/L
83%
53%
21%
96%
AUC = area under the curve; PPV = positive predictive value, NPV = negative predictive value.
Supplemental table III: Correlations between biomarkers
NT-proBNP
Hs-cTnT
Hs-CRP
Cystatin-C
Galectin-3
NT-proBNP
-
-
-
-
-
Hs-cTnT
0.55*
-
-
-
-
Hs-CRP
0.29*
0.29*
-
-
-
Cystatin-C
0.46*
0.46*
0.19*
-
-
Galectin-3
0.45*
0.45*
0.32*
0.70*
-
* P<0.001
Supplemental table IV: Reclassification table for adding hs-cTnT, hs-CRP and Cys-C to
clinical risk factors
Risk categories in clinical risk model
with hs-cTnT, hs-CRP and Cys-C
Risk categories in
0-2%
2-15%
>15%
0-2%
-
-
-
2-15%
1
12
10
0
5
50
0-2%
31
5
0
2-15%
130
192
27
0
51
89
0-2%
31
5
0
2-15%
131
204
37
0
56
139
clinical risk model
Cases (n=78)
>15%
Controls (n=525)
>15%
Total (n=603)
>15%
Supplemental figure 1. Predicted versus observed 90-day mortality rate of MARKEDrisk score categories.
Each dot resembles the patient group within a marked risk score category, from 0 to 7.