To evaluate the diagnostic value of Copeptin as a novel biomarker in early diagnosis of Acute Myocardial Infarction. 56 patients with acute Myocardial Infarction (STEMI) and 25 healthy controls who were admitted to the Cardiology and Clinical Pathology Departments, national heart institute (NHI) from October 2015 to April 2016. The kit used a double-antibody sandwich enzyme-linked immune-sorbent assay (ELISA) to assay the level of Human Copeptin in samples. As regard copeptin, the median range of copeptin level was 242.5pg/ml in patient group and 75pg/ml in control group. The comparative study between the two groups shows a significant difference (p < 0.05) Conclusion: Copeptin is a reliable diagnostic tool in patients with AMI (STEMI) with sensitivity 85.7%, specificity 86.7%, PPV 96% and NPV 61.9%.
3. Copeptin as a Novel Biomarker in the Diagnosis of Acute Myocardial Infarction
Int. J. Cardiol. Cardiovasc. Res. 074
As regard dyslipidemia, of the fifty-six patients in group I,
54 (96.4%) were non-dyslipidemic and 6 (10.7%) were
dyslipidemic; whereas all the twenty-five healthy controls
in group II (100%) were non-dyslipidemic. The
comparative study between the two groups shows no
significant difference (p > 0.05). Other risk factor shows no
significant difference where all of them shows (p> 0.05).
Table 1: Baseline characteristic of the study
population
Baseline
characteristic
Control
group
(N=25)
STEMI group
(N=56)
p-value
Age (years) 51±9 56±9 0.056
male gender 15 (60%) 41 (73.2%) 0.351
Smoking 3 (12%) 30 (53.6%) 0.008
DM 3 (12%) 24 (42.9%) 0.040
HTN 5 (20%) 24 (42.9%) 0.139
Dyslipidemia 0 (0.0%) 6 (10.7%) 0.331
Obesity 0 (0.0%) 5 (8.9%) 0.557
Past history of CAD 0 (0.0%) 4 (7.1%) 0.572
Family history of CAD 0 (0.0%) 1 (1.8%) 1.000
CKD 0 (0.0%) 1 (1.8%) 1.000
Heart block 0 (0.0%) 1 (1.8%) 1.000
Data are presented as mean ± SD; CAD=coronary artery
disease; CKD=chronic kidney disease; DM=diabetes
mellitus; HTN=hypertension; N=number
Figure 1: Prevalence of relevant risk factors and co-
morbidities among cases with STEMI and controls.
Comparison of cardiac markers in cases with STEMI
and control groups
As shown in (Table 2) (figure 2,3,4): Regarding CK-T, the
median range of CK-T level was 143.5 IU/L in patient
group and 66 IU/L in control group. The comparative study
between the two groups shows a significant difference (p
<0.05). In troponin T, the median range of CTnT level was
45.4pg/ml in patient group and 8.26pg/ml in control group.
The comparative study between the two groups shows a
significant difference (p < 0.05). Regarding copeptin, the
median range of copeptin level was 242.5pg/ml in patient
group and 75pg/ml in control group. The comparative
study between the two groups shows a significant
difference (p < 0.05).
Table 2: Comparison of cardiac markers in cases with
STEMI and control groups:
Control group
(N=25)
STEMI group
(N=56)
p-value
Total CK
(IU/ml)
66 (49.8 to 78.5) 143.5 (98 to 176) <0.001
hs-cTnT
(pg/ml)
8.26 (6.1 to 10.1) 45.4 (15.2 to 132) <0.001
Copeptin
(pg/ml)
75 (46.3 to 107.5)242.5 (137.5 to 975)<0.001
Data area median (interquartile rang e). Mann-Whitney
test.
Figure (2): Box plot showing the hs-cTnT in cases with
STEMI and controls. Box represents the range from the
first to third quartile (interquartile range). Line inside the
box represents the median (second quartile). Whiskers
represent the range between the minimum and maximum
values excluding outliers (rounded markers) and extreme
observations (asterisks).
4. Copeptin as a Novel Biomarker in the Diagnosis of Acute Myocardial Infarction
Al-Kishk et al. 075
Figure 3: Box plot showing the total CK in cases Figure 4: Box plot showing the copeptin in cases with STEMI
with STEMI and controls. Box represents the range and controls. Box represents the range from the first to third
from the first to third quartile (interquartile range). quartile (interquartile range). Line inside the box represents the
Line inside the box represents the median (second median (second quartile). Whiskers represent the range
quartile). Whiskers represent the range between between the minimum and maximum values.
the minimum and maximum values.
Table (3): Receiver-operating characteristic (ROC) curve analysis for discrimination between cases with STEMI
and controls using serum total CK, hs-cTnT, or copeptin
Sample size 81 patients
Positive group (STEMI) 56(78.9%)
Negative group (Controls) 25(21.1%)
Disease prevalence 78.9%
Marker
Index Total CK hscTnT Copeptin
Area under the ROC curve (AUC) 0.929 0.885 0.910
95% CI 0.842 to0.976
0.787 to
0.948
0.818 to
0.965
z statistic 13.409 9.626 11.917
p-value <0.0001 <0.0001 <0.0001
Youden index J 0.808 0.688 0.724
Cut-off criterion >80 IU/ml
>12.9
(pg/ml)
>110
(pg/ml)
Sensitivity 87.5 82.14 85.71
95% CI 75.9 - 94.8 69.6 - 91.1 73.8 - 93.6
Specificity 73.33 86.67 86.67
95% CI 68.1 - 99.8 59.5 - 98.3 59.5 - 98.3
+LR 13.13 6.16 6.43
95% CI 2.0 - 87.4 1.7 - 22.5 1.8 - 23.5
-LR 0.13 0.21 0.16
95% CI 0.07 - 0.3 0.1 - 0.4 0.08 - 0.3
+PV 98 95.8 96
95% CI 89.4 - 99.9 85.7 - 99.5 86.3 - 99.5
-PV 66.7 56.5 61.9
95% CI 43.0 - 85.4 34.5 - 76.8 38.4 - 81.9
Delong method.
5. Copeptin as a Novel Biomarker in the Diagnosis of Acute Myocardial Infarction
Int. J. Cardiol. Cardiovasc. Res. 076
Figure (5): Receiver-operating characteristic (ROC) curve
for discrimination between cases with STEMI and controls
using hs- cTnT.
At an area under the curve of 92.2% and cut off crition
value of 80 IU/L, CK-T has a sensitivity of 87.5%,
specificity 93 %, positive predictive value 98% and
negative predictive value 66.7 %.
Figure (6): Receiver-operating characteristic (ROC)
curve for discrimination between cases with STEMI and
controls using serum total CK.
At an area under the curve of 88.5% and cut off crition
value of >12.9pg/ml, hs-cTnT has a sensitivity of 82.14%
,specificity 86.67%, positive predictive value 95.8% and
negative predictive value 56.5%
Figure (7): Receiver-operating characteristic (ROC) curve
for discrimination between cases with STEMI and controls
using copeptin.
At an area under the curve of 91% and cut off crition value
of >110pg/ml, copeptin has a sensitivity of 85.71%,
specificity 86.67%, positive predictive value 96% and
negative predictive value 61.9%.
Table (4): Comparison of the receiver-operating
characteristic (ROC) curves for discrimination
between cases with STEMI and controls using serum
total CK, hscTnT, or copeptin
Marker AUC 95% CI
Total CK 0.929 0.842 to 0.976
hs-cTnT 0.885 0.787 to 0.948
Copeptin 0.91 0.818 to 0.965
Comparison ΔAUC 95% CI for ΔAUC Z
p-
value
Total CK versus
Hs-cTnT
0.044 -0.044 to 0.132 0.985 0.325
Total CK versus
Copeptin
0.019 -0.065 to 0.102 0.434 0.664
Hs-cTnT versus
Copeptin
0.02
6
-0.062 to 0.113 0.571 0.568
AUC= Area under the ROC curve; ΔAUC= difference
between AUCs. =Delong method.
6. Copeptin as a Novel Biomarker in the Diagnosis of Acute Myocardial Infarction
Al-Kishk et al. 077
Figure (8): Comparison of the receiver-operating
characteristic (ROC) curves for discrimination between
cases with STEMI and controls using serum total CK, hs-
cTnT, or copeptin.
Table (5): Backward multivariable binary logistic
regression analysis for discrimination between
patients with STEMI and controls
Independent
variable
B SE Wald
p-
value
OR
95% CI for
OR
Total CK
(IU/ml)
0.06 0.02 7.52 0.006 1.06
1.02 to
1.10
Copeptin
(pg/ml)
0.03 0.01 5.22 0.022 1.03
1.005 to
1.064
Constant -8.66
Variables excluded from the model
hs-cTnT, Smoking, DM, Age, DBP
B=regression coefficient; SE=standard error; Wald=Wald
statistic; OR=odds ratio.
According to Backward multivariable binary logistic
regression analysis for discrimination between patients
with STEMI and controls there is significant in dependable
variable CK-T and copeptin p value <0.05.
Table (6): Correlation between cardiac markers and
other relevant quantitative variables
Total CKhs-cTnT Copeptin
Total CK
Correlation
coefficient
- 0.31 0.20
p-value - 0.009 0.093
hs-cTnT
Correlation
coefficient
0.31 - 0.47
p-value 0.009 - <0.0001
Copeptin
Correlation
coefficient
0.20 0.47 -
p-value 0.093 <0.0001 -
Age
Correlation
coefficient
0.15 0.01 -0.05
p-value 0.207 0.913 0.656
Duration of
chest pain
Correlation
coefficient
0.82 0.10 -0.13
p-value <0.0001 0.467 0.336
SBP
Correlation
coefficient
0.11 -0.01 0.07
p-value 0.383 0.926 0.550
DBP
Correlation
coefficient
0.11 -0.02 0.13
p-value 0.359 0.899 0.291
Spearman rank correlation; SBP= systolic blood pressure;
DBP= diastolic blood pressure
According to the previous table there is statistically
significant correlation between CK-T and hs-cTnT p value
<0.05and there is statistically significant correlation
between hs-cTnT and Copeptin p value <0.05. And there
is statistically significant correlation between CK-T and
SBP with p value <0.001.
DISCUSSION
Myocardial infarction (MI) can be recognized by clinical
features, including electrocardiographic (ECG) findings,
elevated values of biochemical markers (biomarkers) of
myocardial necrosis, and by imaging, or may be defined
by pathology. The development of ever more sensitive and
myocardial tissue-specific cardiac biomarkers and more
sensitive imaging techniques now allows for detection of
very small amounts of myocardial injury or necrosis
(Thygesen et al., 2012).
Copeptin is a strong marker for mortality and morbidity in
patients with heart failure after an acute MI. It is released
very early during the onset of an acute myocardial
infarction (AMI), raising the question of its potential value
in the diagnosis of AMI and particularly in ruling-out AMI.
Indeed, copeptin is released much earlier than Troponin
making the interpretation of their complementary kinetics
a useful tool to rule-out AMI (Maisel et al., 2013).
The aim of this work was to detect the diagnostic value of
Copeptin as a novel biomarker in early diagnosis of acute
myocardial infarction. We have enrolled 56 patients with
acute Myocardial Infarction-on (S.T.E.M.I.) and 15 healthy
controls who are admitted to the Cardiology and Clinical
Pathology Departments at national heart institute. The
principal finding of current study was that copeptin has a
sensitivity of 85.71%, specificity of 86.67%, positive
predictive value of 96% and negative predictive value of
61.9% with an accuracy of 86%. (cutoff value of 110 pg/ml)
while, cardiac troponin T has a sensitivity of 82.14 %,
specificity of 86.67 %, positive predictive value of 95.8%
and negative predictive value of 56.5% with an accuracy
of 85%. (Cutoff value of 12.9 pg/ml) but CK-T has a
sensitivity of 80%, specificity of 73%, positive predictive