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Use of Copeptin in Acute Myocardial Infarction Ten Consent Was Obtained for Every Patient In- Results Cluded in the Study

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Use of Copeptin in Acute Myocardial Infarction Ten Consent Was Obtained for Every Patient In- Results Cluded in the Study European Review for Medical and Pharmacological Sciences 2017; 21: 1576-1582 Diagnostic value of copeptin in acute myocardial infarction M.O. AY1, A.K. ERENLER1, T. DOGAN2, M. YETIM2 1Department of Emergency Medicine, Hitit University, Corum Training and Research Hospital, Corum, Turkey 2Department of Cardiology, Hitit University, Corum Training and Research Hospital, Corum, Turkey Abstract. – OBJECTIVE: The aim of this study cy departments (EDs). Recently, many poten- was to investigate the effectiveness of copeptin tial biomarkers have been studied for the ear- in the early diagnosis of acute myocardial infarc- ly and appropriate diagnosis of AMI. Cardiac tion (AMI), and to compare the diagnostic effica- troponin I (cTnI) and troponin T are commonly cy of copeptin with other cardiac markers. PATIENTS AND METHODS: A total of 160 cas- used for determining the extent of cardiac mu- es were enrolled in the study. All were over 18 scle injury in AMI. However, studies for novel years of age, and consisted of 54 non-ST eleva- early diagnostic biomarkers continue. One such tion MI (NSTEMI), 54 ST segment elevation MI biomarker is copeptin, a 39-amino-acid peptide (STEMI), and 52 healthy subjects (controls). Se- on the C-terminal portion of pro-arginine vaso- rum troponin-I, CK-MB mass, copeptin and CRP pressin that is synthesized and released along levels were measured in each of the cases, and 1,2 were compared between the three groups for with arginine vasopressin . Recent works sug- statistical differences. gest that there is a strong relationship between RESULTS: The copeptin levels in the STEMI elevated serum levels of copeptin and diseases, (p < 0.001) and NSTEMI (p = 0.042) groups were such as lower respiratory tract infection, sepsis, found to be significantly higher than the control stroke, and acute pancreatitis. It has been re- group. Spearman’s correlation analysis showed ported that copeptin levels in patients with AMI a significant positive correlation between the lev- are higher than that of controls3. There are also el of copeptin and the presence of AMI (r = 0.285, p < 0.001), CK-MB mass (r = 0.246, p = 0.002), and studies suggesting that the use of copeptin as troponin-I (r = 0.199, p = 0.012). Sensitivity, spec- a non-specific marker, together with troponins, ificity, and AUC values of the tests, according to may exclude the diagnosis of AMI, with a ne- ROC analysis performed for the diagnosis of AMI gative predictive value ranging from 97% to were; troponin-I > 0.1 ng/mL (71.0%, 100.0%, and 100% in patients presented to EDs with acute 0.855); CK-MB mass > 3.59 ng/mL (77.8%, 92.3%, chest pain4,5. However, currently, there are no and 0.911); CRP > 6.37 mg/L (53.7%, 88.5%, and 0.769); and copeptin > 2.47 ng/mL (66.7%, 75.0%, studies on the use of copeptin to diagnose acute and 0.676), respectively (p < 0.001). myocardial infarction in the Turkish population. CONCLUSIONS: Cardiac troponin remains the In this study, our aim was to determine the gold standard biomarker for the diagnostic eval- diagnostic value of copeptin in comparison with uation of AMI. Copeptin can be used as a diag- other commonly used markers, in Turkish AMI nostic marker in patients with suspected AMI in patients. combination with other biomarkers, but, copeptin alone should not be considered as a single diag- nostic marker in patients with suspected AMI. Patients and Methods Key Words: Acute myocardial infarction, Diagnosis, Copeptin, The study was approved by the local Ethics Troponin-I, CK-MB, CRP. Committee. Patients were enrolled into the stu- dy after being admitted to the ED for AMI. A total of 108 patients, aged 18 years or over, and Introduction 52 healthy controls were included in the stu- dy. Patients were divided into two subgroups; Acute myocardial infarction (AMI) is one Group I, with non ST-elevated MI (n = 54), and of the most common complaints in emergen- Group II, with ST-elevated MI (n = 54). Writ- 1576 Corresponding Author: Mehmet Oguzhan Ay, MD; e-mail: [email protected] Use of copeptin in acute myocardial infarction ten consent was obtained for every patient in- Results cluded in the study. Exclusion criteria were as follows: patients under the age of 18, patients Demographic details and laboratory findings of with chronic renal failure, patients with creati- Groups I and II, and the healthy controls are given ne levels over 1.5 mg/dL, patients with normal in Table I. The percentage of males in Groups I cTnI levels in the follow-up, and patients wi- and II, and healthy controls were 57.7%, 61.1%, thout AMI. A standard form was obtained, and and 87.0%, respectively. In Group II, the rate of gender, age, body-mass index (BMI), previous male gender was found to be significantly higher, diseases (e.g., hypertension (HT), diabetes mel- when compared to Group I (p = 0.002), and heal- litus (DM), coronary artery disease (CAD), thy controls (p = 0.001). The mean age was found hyperlipidemia, and renal failure), smoking to be 60.1 ± 11.1, 59.5 ± 9.6, and 55.3 ± 12.6 ye- status, family history of heart diseases, ECG ars in Groups I and II, and healthy controls, re- findings (non-ST or ST-elevated AMI), and spectively. The mean age of patients in Group I outcomes (hospitalization, transfer, discharge was found to be significantly higher than controls from the ED) of the patients and controls were (p = 0.040). recorded. When groups were compared according to For the laboratory measurement of copeptin, BMI, Group I had a significantly higher mean va- 2 mL of whole venous blood was obtained from lue than Group II (p = 0.012). Similarly, smoking patients on admission. The samples were centrifu- status was significantly different between the ged at 3500 rpm for 10 minutes to separate the se- groups, with the highest percentage being in rum. Samples were stored at -80°C until analysis. Group II (70.4%, p < 0.05).When the rate of HT Measurements of cTnI and creatine kinase-MB history was analyzed, group II had the highest isoenzyme (CK-MB) were performed on the Ro- rate compared with group I, and healthy controls che Cobas E601 immunology analyzer (Roche® (57.4%, p = 0.032). Type II DM was most com- Diagnostics, Mannheim, Baden-Württemberg, monly seen in group I, and this finding was sta- Germany) using the electrochemiluminescence tistically significant when compared to the other immunoassay method. Measurement of CRP was groups (40.7%). The rate of hyperlipidemia was performed on the Roche Cobas E501 chemistry significantly higher in groups I and II, compared analyzer (Roche® Diagnostics, Mannheim, Ba- with healthy controls (p < 0.001). There were no den-Württemberg, Germany) using the immu- significant differences for family history of CAD noturbidimetric method. Measurement of serum between the two patient groups, but the healthy copeptin was performed using the Human Copep- controls were found to have slightly smaller rates tin ELISA kit (Sunred Biological Technology®, of CAD in the family than group I (p = 0.047). Shangai, People’s Republic of China) and read on When laboratory findings of the participants the Synergy HT microplate reader (Biotek®, Wi- were investigated, it was found that CK-MB le- nooski, VT, USA). vels were significantly different between all three groups. In Group II, CK-MB levels were 6-fold Statistical Analysis higher than that of Group I (p < 0.001). Similarly, Statistical analysis was done using Statisti- cTnI levels were significantly different between cal Package for the Social Sciences (SPSS®, groups. Group II showed the highest elevation of SPSS Inc., Chicago, IL, USA). The Kolmogo- serum cTnI (p < 0.001). Serum levels of CRP in rov-Smirnov test was used to test for normali- Groups I and II were significantly higher than he- ty of the data. Normally distributed data were althy controls (p < 0.001). analyzed using the independent t-test, and pre- Median serum copeptin levels (ng/mL) were sented as mean ± standard deviation. Data that found to be 2.22 (2.18-2.35), 2.50 (2.34-2.72), was not normally distributed were analyzed and 2.94 (2.85-3.24) in healthy controls, group I, using the Mann-Whitney U test, and presented and group II, respectively. In group II, serum le- as median with 95% confidence interval. Fre- vels of copeptin were found to be significantly hi- quencies were analyzed using the Chi-square gher than that of group I and healthy controls (p < test, and presented as numbers and percentages. 0.001). Additionally, the copeptin levels in Group To evaluate the diagnostic value of laboratory I were significantly higher than healthy controls findings, Receiver Operating Characteristic (p = 0.042). Table I and Figure 1 represent the (ROC) analysis was performed. A p value of < comparison of serum copeptin levels between the 0.05 was considered as statistically significant. patient groups and healthy controls. 1577 M.O. Ay, A.K. Erenler, T. Dogan, M. Yetim Table I. Comparison of demographical and laboratory findings of groups I, II, and healthy controls. p Control (0) NSTEMI (1) STEMI (2) 0 vs. 1 0 vs. 2 1 vs. 2 Demographical findings n (M/F; Male %) 52 54 54 (30/22; 57.7%) (33/21; 61.1%) (47/7; 87.0%) 0.721 0.001 0.002 Age (year) 55.3 ± 12.6 60.1 ± 11.1 59.5 ± 9.6 0.040 0.051 0.796 BMI (kg/m2) 28.2 ± 4.5 28.8 ± 4.1 26.9 ± 3.5 0.449 0.114 0.012 Smoking (n, %) 13 (25.0%) 27 (50.0%) 38 (70.4%) 0.008 <0.001 0.031 Hypertension (n, %) 19 (36.5%) 30 (55.6%) 31 (57.4%) 0.051 0.032 0.847 Type 2 diabetes (n, %) 4 (7.7%) 22 (40.7%) 12 (22.2%) <0.001 0.038 0.039 Hyperlipidemia (n, %) 2 (3.8%) 16 (29.6%) 17 (31.5%) <0.001 <0.001 0.835 Family history of CAD (n, %) 17 (32.7%) 28 (51.9%) 21 (38.9%) 0.047 0.508 0.178 Laboratory findings* CK-MB mass (ng/mL) 1.46 4.84 28.98 (1.23-1.89) (3.30-9.09) (13.66-46.21) <0.001 <0.001 <0.001 Troponin-I (ng/mL) 0.10 0.19 2.49 (0.10-0.10) (0.10-0.50) (1.04-5.09) <0.001 <0.001 <0.001 CRP (mg/L) 1.79 5.68 7.27 (1.43-3.15) (3.86-14.74) (4.96-9.72) <0.001 <0.001 0.178 Copeptin (ng/mL) 2.22 2.50 2.94 (2.18-2.35) (2.34-2.72) (2.85-3.24) 0.042 <0.001 <0.001 M: Male; F: Female; BMI: Body mass index; CAD<0.001: Coronary artery disease.
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