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FOCUS ISSUE: BIOMARKERS IN CARDIOVASCULAR DISEASE: CLINICAL RESEARCH: BIOMARKERS IN ACS

Copeptin Improves Early Diagnosis of Acute Myocardial Infarction

Till Keller, MD^_*, Stergios Tzikas, MD^_*, Tanja Zeller, PhD^_*, Ewa Czyz, MD^_*, Lars Lillpopp^_*, Francisco M. Ojeda, PhD^_*, Alexander Roth, PhD^_*, Christoph Bickel, MD, Stephan Baldus, MD, Christoph R. Sinning, MD^_*, Philipp S. Wild, MD^_*, Edith Lubos, MD^_*,||, Dirk Peetz, MD, Jan Kunde, PhD^¶, Oliver Hartmann, MSc^¶, Andreas Bergmann, PhD^¶, Felix Post, MD^_*, Karl J. Lackner, MD, Sabine Genth-Zotz, MD^_*, Viviane Nicaud, MA^#, Laurence Tiret, PhD^#, Thomas F. Münzel, MD^_* and Stefan Blankenberg, MD^_*,_*

^_* Department of Medicine II, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
Institute for Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany
Department of Internal Medicine, Federal Armed Hospital, Koblenz, Germany
Department of Cardiology, Heart Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany
^|| Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
^¶ B.R.A.H.M.S. AG, Henningsdorf, Germany
^# INSERM, UMRS 937, Université Pierre et Marie Curie, Paris, France

Manuscript received October 22, 2009; revised manuscript received December 17, 2009, accepted January 2, 2010.

^_* Reprint requests and correspondence: Dr. Stefan Blankenberg, Department of Medicine II, Johannes Gutenberg-University, Langenbeckstrasse 1, 55101 Mainz, Germany (Email: stefan.blankenberg{at}unimedizin-mainz.de).

Objectives: Early identification of myocardial infarction in chest pain patients is crucial to identify patients at risk and to maintain a fast treatment initiation.

Background: The aim of the current investigation is to test whether determination of copeptin, an indirect marker for arginin-vasopressin, adds diagnostic information to cardiac troponin in early evaluation of patients with suspected myocardial infarction.

Methods: Between January 2007 and July 2008, patients with suspected acute coronary syndrome were consecutively enrolled in this multicenter study. Copeptin, troponin T (TnT), myoglobin, and creatine kinase-myocardial band were determined at admission and after 3 and 6 h.

Results: Of 1,386 (66.4% male) enrolled patients, 299 (21.6%) had the discharge diagnosis of acute myocardial infarction, 184 (13.3%) presented with unstable angina, and in 903 (65.2%) an acute coronary syndrome could be excluded. Combined measurement of copeptin and TnT on admission improved the c-statistic from 0.84 for TnT alone to 0.93 in the overall population and from 0.77 to 0.9 in patients presenting within 3 h after chest pain onset (CPO) (p < 0.001). In this group the combination of copeptin with a conventional TnT provided a negative predictive value of 92.4%.

Conclusions: In triage of chest pain patients, determination of copeptin in addition to troponin improves diagnostic performance, especially early after CPO. Combined determination of troponin and copeptin provides a remarkable negative predictive value virtually independent of CPO time and therefore aids in early and safe rule-out of myocardial infarction.

Key Words: chest pain • copeptin • diagnosis • myocardial infarction • troponin

Abbreviations and Acronyms   ACS = acute coronary syndrome   AMI = acute myocardial infarction   AUC = area under the curve   AVP = arginin-vasopressin   CK-MB = creatine kinase-myocardial band   CPO = chest pain onset   CV = coefficient of variation   ECG = electrocardiogram/electrocardiographic   MI = myocardial infarction   NCCP = noncoronary chest pain   NPV = negative predictive value   NT-proBNP = N-terminal pro-brain natriuretic peptide   PPV = positive predictive value   ROC = receiver operating characteristic   TnI = troponin I   TnT = troponin T   UAP = unstable angina pectoris

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