Performance of Copeptin for Early Diagnosis of Acute Coronary Syndromes: A Systematic Review and Meta-Analysis of 14,139 Patients

Lukasz Szarpak, Marcin Lapinski, Aleksandra Gasecka, Michal Pruc, Wiktoria L Drela, Mariusz Koda, Andrea Denegri, Frank W Peacock, Miłosz J Jaguszewski, Krzysztof J Filipiak, Lukasz Szarpak, Marcin Lapinski, Aleksandra Gasecka, Michal Pruc, Wiktoria L Drela, Mariusz Koda, Andrea Denegri, Frank W Peacock, Miłosz J Jaguszewski, Krzysztof J Filipiak

Abstract

Diagnosis of acute coronary syndrome (ACS) based on copeptin level may enable one to confirm or rule-out acute myocardial infarction (AMI) with higher sensitivity and specificity, which may in turn further reduce mortality rate and decrease the economic costs of ACS treatment. We conducted a systematic review and meta-analysis to investigate the relationship between copeptin levels and type of ACS. We searched Scopus, PubMed, Web of Science, Embase, and Cochrane to locate all articles published up to 10 October 2021. We evaluated a meta-analysis with random-effects models to evaluate differences in copeptin levels. A total of 14,139 patients (4565 with ACS) were included from twenty-seven studies. Copeptin levels in AMI and non-AMI groups varied and amounted to 68.7 ± 74.7 versus 14.8 ± 19.9 pmol/L (SMD = 2.63; 95% CI: 2.02 to 3.24; p < 0.001). Copeptin levels in the AMI group was higher than in the unstable angina (UAP) group, at 51.9 ± 52.5 versus 12.8 ± 19.7 pmol/L (SMD = 1.53; 95% CI: 0.86 to 2.20; p < 0.001). Copeptin levels in ST-elevation myocardial infarction (STEMI) versus non-ST elevation myocardial infarction (NSTEMI) patient groups were 54.8 ± 53.0 versus 28.7 ± 46.8 pmol/L, respectively (SMD = 1.69; 95% CI: = 0.70 to 4.09; p = 0.17). In summary, elevated copeptin levels were observed in patients with ACS compared with patients without ACS. Given its clinical value, copeptin levels may be included in the assessment of patients with ACS as well as for the initial differentiation of ACS.

Keywords: acute coronary syndrome; acute myocardial infarction; biomarker; copeptin; systematic review.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram showing stages of the database search and study selection as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
Figure 2
Figure 2
Forest plot of copeptin levels in the AMI and no-AMI groups. The center of each square represents the weighted standard mean difference for individual trials, and the corresponding horizontal line stands for a 95% confidence interval. The diamonds represent pooled results. Legend: CI = confidence interval; SMD = standard mean difference.
Figure 3
Figure 3
Forest plot of copeptin levels in the AMI and UAP groups. The center of each square represents the weighted standard mean difference for individual trials, and the corresponding horizontal line stands for a 95% confidence interval. The diamonds represent pooled results. Legend: CI = confidence interval; SMD = standard mean difference.
Figure 4
Figure 4
Forest plot of copeptin levels in the STEMI and NSTEMI groups. The center of each square represents the weighted standard mean difference for individual trials, and the corresponding horizontal line stands for a 95% confidence interval. The diamonds represent pooled results. Legend: CI = confidence interval; SMD = standard mean difference.

References

    1. Lüscher T.F. Outcomes of acute coronary syndromes: Clinical presentation, gender, inflammation, and cell therapy. Eur. Heart J. 2017;38:125–129. doi: 10.1093/eurheartj/ehw676.
    1. Sugiyama T., Hasegawa K., Kobayashi Y., Takahashi O., Fukui T., Tsugawa Y. Differential time trends of outcomes and costs of care for acute myocardial infarction hospitalizations by ST elevation and type of intervention in the United States, 2001–2011. J. Am. Heart Assoc. 2015;4:e001445. doi: 10.1161/JAHA.114.001445.
    1. DeVon H.A., Hogan N., Ochs A.L., Shapiro M. Time to treatment for acute coronary syndromes: The cost of indecision. J. Cardiovasc. Nurs. 2010;25:106–114. doi: 10.1097/JCN.0b013e3181bb14a0.
    1. McNamara R.L., Wang Y., Herrin J., Curtis J.P., Bradley E.H., Magid D.J., Peterson E.D., Blaney M., Frederick P.D., Krumholz H.M., et al. Effect of door-to-balloon time on mortality in patients with ST-segment elevation myocardial infarction. J. Am. Coll. Cardiol. 2006;47:2180–2186. doi: 10.1016/j.jacc.2005.12.072.
    1. Body R. Acute coronary syndromes diagnosis, version 2.0: Tomorrow’s approach to diagnosing acute coronary syndromes? Turk. J. Emerg. Med. 2018;18:94–99. doi: 10.1016/j.tjem.2018.05.005.
    1. Birnbaum Y., Wilson J.M., Fiol M., de Luna A.B., Eskola M., Nikus K. ECG diagnosis and classification of acute coronary syndromes. Ann. Noninvasive Electrocardiol. 2014;19:4–14. doi: 10.1111/anec.12130.
    1. Willemsen R.T., Kietselaer B.L., Kusters R., Buntinx F., Dinant G.J. Diagnostic tools for acute coronary syndrome (ACS): A challenge for general practitioners and cardiologists. Ned. Tijdschr. Geneeskd. 2014;158:A8078.
    1. Bozkurt S., Kaya E.B., Okutucu S., Aytemir K., Coskun F., Oto A. The diagnostic and prognostic value of first hour glycogen phosphorylase isoenzyme BB level in acute coronary syndrome. Cardiol. J. 2011;18:496–502. doi: 10.5603/CJ.2011.0004.
    1. Shah A.S.V., Anand A., Strachan F.E., Ferry A.V., Lee K.K., Chapman A.R., Sandeman D., Stables C.L., Adamson P.D., Andrews J.P.M., et al. High-sensitivity troponin in the evaluation of patients with suspected acute coronary syndrome: A stepped-wedge, cluster-randomised controlled trial. Lancet. 2018;392:919–928. doi: 10.1016/S0140-6736(18)31923-8.
    1. Jaffe A.S., Ordonez-Llanos J. High—Sensitivity cardiac troponin: From theory to clinical practice. Rev. Esp. Cardiol. 2013;66:687–691. doi: 10.1016/j.recesp.2013.04.021.
    1. Liebetrau C., Nef H., Szardien S., Dörr O., Willmer M., Voss S., Troidl C., Hoffmann J., Rixe J., Rolf A., et al. Release kinetics of copeptin in patients undergoing transcoronary ablation of septal hypertrophy. Clin. Chem. 2013;59:566–569. doi: 10.1373/clinchem.2012.194001.
    1. Möckel M., Searle J. Copeptin-marker of acute myocardial infarction. Curr. Atheroscler. Rep. 2014;16:421. doi: 10.1007/s11883-014-0421-5.
    1. Katan M., Christ-Crain M. The stress hormone copeptin: A new prognostic biomarker in acute illness. Swiss Med. Wkly. 2010;140:w13101. doi: 10.4414/smw.2010.13101.
    1. Yang Y., Gao S., Fang Q., Yang J. Diagnostic value of copeptin combined with hypersensitive cardiac troponin T detection in early acute myocardial infarction: A prrotocol of randomized double-blind diagnostic trial. Medicine. 2021;100:e23949. doi: 10.1097/MD.0000000000023949.
    1. Page M.J., McKenzie J.E., Bossuyt P.M., Boutron I., Hoffmann T.C., Mulrow C.D., Shamseer L., Tetzlaff J.M., Akl E.A., Brennan S.E., et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. J. Clin. Epidemiol. 2021;134:178–189. doi: 10.1016/j.jclinepi.2021.03.001.
    1. Hozo S.P., Djulbegovic B., Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med. Res. Methodol. Springer. 2005;5:13. doi: 10.1186/1471-2288-5-13.
    1. Ades A.E., Lu G., Higgins J.P.T. The interpretation of random-effects meta-analysis in decision models. Med. Decis. Mak. 2005;25:646–654. doi: 10.1177/0272989X05282643.
    1. Egger M., Davey Smith G., Schneider M., Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315:629–634. doi: 10.1136/bmj.315.7109.629.
    1. Begg C.B., Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50:1088–1101. doi: 10.2307/2533446.
    1. Ahmed T.A.N., Johny J.S., Abdel-Malek M.Y., Fouad D.A. The additive value of copeptin for early diagnosis and prognosis of acute coronary syndromes. Am. J. Emerg. Med. 2021;50:413–421. doi: 10.1016/j.ajem.2021.08.069.
    1. Alquézar A., Santaló M., Rizzi M., Gich I., Grau M., Sionis A., Ordóñez-Llanos J., Investigadores del Estudio TUSCA Combined high-sensitivity copeptin and troponin T evaluation for the diagnosis of non-ST elevation acute coronary syndrome in the emergency department. Emergencias. 2017;29:237–244.
    1. Ay M.O., Erenler A.K., Dogan T., Yetim M. Diagnostic value of copeptin in acute myocardial infarction. Eur. Rev. Med. Pharm. Sci. 2017;21:1576–1582.
    1. Bahrmann P., Bahrmann A., Breithardt O.A., Daniel W.G., Christ M., Sieber C.C., Bertsch T. Additional diagnostic and prognostic value of copeptin ultra-sensitive for diagnosis of non-ST-elevation myocardial infarction in older patients presenting to the emergency department. Clin. Chem. Lab. Med. 2013;51:1307–1319. doi: 10.1515/cclm-2012-0401.
    1. Boeddinghaus J., Reichlin T., Nestelberger T., Twerenbold R., Meili Y., Wildi K., Hillinger P., Giménez M.R., Cupa J., Schumacher L., et al. Early diagnosis of acute myocardial infarction in patients with mild elevations of cardiac troponin. Clin. Res. Cardiol. 2017;106:457–467. doi: 10.1007/s00392-016-1075-9.
    1. Charpentier S., Maupas-Schwalm F., Cournot M., Elbaz M., Botella J.M., Lauque D. Combination of copeptin and troponin assays to rapidly rule out non-ST elevation myocardial infarction in the emergency department. Acad. Emerg. Med. 2012;19:517–524. doi: 10.1111/j.1553-2712.2012.01350.x.
    1. Duchenne J., Mestres S., Dublanchet N., Combaret N., Marceau G., Caumon L., Dutoit L., Ughetto S., Motreff P., Sapin V., et al. Diagnostic accuracy of copeptin sensitivity and specificity in patients with suspected non-ST-elevation myocardial infarction with troponin I below the 99th centile at presentation. BMJ Open. 2014;4:e004449. doi: 10.1136/bmjopen-2013-004449.
    1. Gaber M.A., Omar O.H.M., El-Deek S.E.M., Hassan A.K.M., Mahmoud M.S., Meki A.M.A. Copeptin, miRNA-208, and miRNA-499 as New Biomarkers for Early Detection of Acute Coronary Syndrome. Appl. Biochem. Biotechnol. 2021 doi: 10.1007/s12010-021-03726-2.
    1. Hillinger P., Twerenbold R., Jaeger C., Wildi K., Reichlin T., Rubini Gimenez M., Engels U., Miró O., Boeddinghaus J., Puelacher C., et al. Optimizing Early Rule-Out Strategies for Acute Myocardial Infarction: Utility of 1-Hour Copeptin. Clin. Chem. 2015;61:1466–1474. doi: 10.1373/clinchem.2015.242743.
    1. Jacobs L.H.J., van Borren M., Gemen E., van Eck M., van Son B., Glatz J.F.C., Daniels M., Kusters R. Rapidly rule out acute myocardial infarction by combining copeptin and heart-type fatty acid-binding protein with cardiac troponin. Ann. Clin. Biochem. 2015;52:550–561. doi: 10.1177/0004563215578189.
    1. Jeong J.H., Seo Y.H., Ahn J.Y., Kim K.H., Young Seo J., Chun K.Y., Lim Y.S., Park P.W. Performance of Copeptin for Early Diagnosis of Acute Myocardial Infarction in an Emergency Department Setting. Ann. Lab. Med. 2020;40:7–14. doi: 10.3343/alm.2020.40.1.7.
    1. Keller T., Tzikas S., Zeller T., Czyz E., Lillpopp L., Ojeda F.M., Roth A., Bickel C., Baldus S., Sinning C.R., et al. Copeptin improves early diagnosis of acute myocardial infarction. J. Am. Coll. Cardiol. 2010;55:2096–2106. doi: 10.1016/j.jacc.2010.01.029.
    1. Khan S.Q., Dhillon O.S., O’Brien R.J., Struck J., Quinn P.A., Morgenthaler N.G., Squire I.B., Davies J.E., Bergmann A., Ng L.L. C-terminal provasopressin (copeptin) as a novel and prognostic marker in acute myocardial infarction: Leicester Acute Myocardial Infarction Peptide (LAMP) study. Circulation. 2007;115:2103–2110. doi: 10.1161/CIRCULATIONAHA.106.685503.
    1. Kim K.S., Suh G.J., Song S.H., Jung Y.S., Kim T., Shin S.M., Kang M.W., Lee M.S. Copeptin with high-sensitivity troponin at presentation is not inferior to troponin measurements for ruling out acute myocardial infarction. Clin. Exp. Emerg. Med. 2020;7:35–42. doi: 10.15441/ceem.19.013.
    1. Lotze U., Lemm H., Heyer A., Müller K. Combined determination of highly sensitive troponin T and copeptin for early exclusion of acute myocardial infarction: First experience in an emergency department of a general hospital. Vasc. Health Risk Manag. 2011;7:509–515. doi: 10.2147/VHRM.S21753.
    1. Maisel A., Mueller C., Neath S.X., Christenson R.H., Morgenthaler N.G., McCord J., Nowak R.M., Vilke G., Daniels L.B., Hollander J.E., et al. Copeptin helps in the early detection of patients with acute myocardial infarction: Primary results of the CHOPIN trial (Copeptin Helps in the early detection Of Patients with acute myocardial INfarction) J. Am. Coll. Cardiol. 2013;62:150–160. doi: 10.1016/j.jacc.2013.04.011.
    1. Mauermann E., Bolliger D., Seeberger E., Puelacher C., Corbiere S., Filipovic M., Seeberger M., Mueller C., Buse G.L. Incremental Value of Preoperative Copeptin for Predicting Myocardial Injury. Anesth. Analg. 2016;123:1363–1371. doi: 10.1213/ANE.0000000000001635.
    1. Meune C., Zuily S., Wahbi K., Claessens Y.E., Weber S., Chenevier-Gobeaux C. Combination of copeptin and high-sensitivity cardiac troponin T assay in unstable angina and non-ST-segment elevation myocardial infarction: A pilot study. Arch. Cardiovasc. Dis. 2011;104:4–10. doi: 10.1016/j.acvd.2010.11.002.
    1. Morawiec B., Przywara-Chowaniec B., Muzyk P., Opara M., Ho L., Tat L.C., Muller O., Nowalany-Kozielska E., Kawecki D. Combined Use of High-Sensitive Cardiac Troponin, Copeptin, and the Modified HEART Score for Rapid Evaluation of Chest Pain Patients. Dis. Markers. 2018;2018:9136971. doi: 10.1155/2018/9136971.
    1. Narayan H., Dhillon O.S., Quinn P.A., Struck J., Squire I.B., Davies J.E., Ng L.L. C-terminal provasopressin (copeptin) as a prognostic marker after acute non-ST elevation myocardial infarction: Leicester Acute Myocardial Infarction Peptide II (LAMP II) study. Clin. Sci. 2011;121:79–89. doi: 10.1042/CS20100564.
    1. Reichlin T., Hochholzer W., Stelzig C., Laule K., Freidank H., Morgenthaler N.G., Bergmann A., Potocki M., Noveanu M., Breidthardt T., et al. Incremental Value of Copeptin for Rapid Rule Out of Acute Myocardial Infarction. J. Am. Coll. Cardiol. 2009;54:60–68. doi: 10.1016/j.jacc.2009.01.076.
    1. Sebbane M., Lefebvre S., Kuster N., Jreige R., Jacques E., Badiou S., Dumont R., Cristol J.P., Dupuy A.M. Early rule out of acute myocardial infarction in ED patients: Value of combined high-sensitivity cardiac troponin T and ultrasensitive copeptin assays at admission. Am. J. Emerg. Med. 2013;31:1302–1308. doi: 10.1016/j.ajem.2013.04.033.
    1. Slagman A., Searle J., Müller C., Möckel M. Temporal Release Pattern of Copeptin and Troponin T in Patients with Suspected Acute Coronary Syndrome and Spontaneous Acute Myocardial Infarction. Clin. Chem. 2015;61:1273–1282. doi: 10.1373/clinchem.2015.240580.
    1. Smaradottir M.I., Ritsinger V., Gyberg V., Norhammar A., Näsman P., Mellbin L.G. Copeptin in patients with acute myocardial infarction and newly detected glucose abnormalities—A marker of increased stress susceptibility? A report from the Glucose in Acute Myocardial Infarction cohort. Diab. Vasc. Dis. Res. 2017;14:69–76. doi: 10.1177/1479164116664490.
    1. Smaradottir M.I., Andersen K., Gudnason V., Näsman P., Rydén L., Mellbin L.G. Copeptin is associated with mortality in elderly people. Eur. J. Clin. Investig. 2021;51:e13516. doi: 10.1111/eci.13516.
    1. Stallone F., Schoenenberger A.W., Puelacher C., Rubini Gimenez M., Walz B., Naduvilekoot Devasia A., Bergner M., Twerenbold R., Wildi K., Reichlin T., et al. Incremental value of copeptin in suspected acute myocardial infarction very early after symptom onset. Eur. Heart J. Acute Cardiovasc. Care. 2016;5:407–415. doi: 10.1177/2048872616641289.
    1. Stengaard C., Sørensen J.T., Ladefoged S.A., Lassen J.F., Rasmussen M.B., Pedersen C.K., Ayer A., Bøtker H.E., Terkelsen C.J., Thygesen K. The potential of optimizing prehospital triage of patients with suspected acute myocardial infarction using high-sensitivity cardiac troponin T and copeptin. Biomarkers. 2017;22:351–360. doi: 10.1080/1354750X.2016.1265008.
    1. Möckel M., Searle J.L., Hamm C., Slagman A., Blankenberg S., Huber K., Katus H., Liebetrau C., Müller C., Muller R., et al. Early discharge using single cardiac troponin and copeptin testing in patients with suspected acute coronary syndrome (ACS): A randomized, controlled clinical process study. Eur. Heart J. 2015;36:369–376. doi: 10.1093/eurheartj/ehu178.
    1. Lu J., Wang S., He G., Wang Y. Prognostic value of copeptin in patients with acute coronary syndrome: A systematic review and meta-analysis. PLoS ONE. 2020;15:e0238288. doi: 10.1371/journal.pone.0238288.
    1. Mueller M., Beitzke D., Scherz T., Loewe C., Mangold A., Marculescu R., Poppe M., Sterz F., Herkner H., Lang I., et al. Copeptin Levels Are Independent from Mild Therapeutic Hypothermia but Do Not Predict Infarct Size in Patients Presenting with ST-Segment Elevation Myocardial Infarction. J. Cardiovasc. Dev. Dis. 2021;8:131. doi: 10.3390/jcdd8100131.

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