CLINICAL RESEARCH: BIOMARKERS
Incremental Value of Copeptin for Rapid Rule Out of Acute Myocardial Infarction
Tobias Reichlin, MD*,
Willibald Hochholzer, MD*,
Claudia Stelzig, MSc*,
Kirsten Laule, MSc*,
Heike Freidank, MD ,
Nils G. Morgenthaler, MD ,
Andreas Bergmann, PhD,
Mihael Potocki, MD*,
Markus Noveanu, MD*,
Tobias Breidthardt, MD*,
Andreas Christ, MD*,
Tujana Boldanova, MD*,
Ramona Merki, MD*,
Nora Schaub, MD*,
Roland Bingisser, MD*,
Michael Christ, MD* and
Christian Mueller, MD*,*
* Department of Internal Medicine, University Hospital, Basel, Switzerland
Department of Laboratory Medicine, University Hospital, Basel, Switzerland
Research Department, Brahms AG, Henningsdorf, Germany
Manuscript received January 4, 2009;
accepted January 28, 2009.
* Reprint requests and correspondence: Prof. Dr. Christian Mueller, Department of Internal Medicine, University Hospital Basel, Petersgraben 4, Basel CH-4031, Switzerland (Email: chmueller{at}uhbs.ch).
Objectives: The purpose of this study was to examine the incremental value of copeptin for rapid rule out of acute myocardial infarction (AMI).
Background: The rapid and reliable exclusion of AMI is a major unmet clinical need. Copeptin, the C-terminal part of the vasopressin prohormone, as a marker of acute endogenous stress may be useful in this setting.
Methods: In 487 consecutive patients presenting to the emergency department with symptoms suggestive of AMI, we measured levels of copeptin at presentation, using a novel sandwich immunoluminometric assay in a blinded fashion. The final diagnosis was adjudicated by 2 independent cardiologists using all available data.
Results: The adjudicated final diagnosis was AMI in 81 patients (17%). Copeptin levels were significantly higher in AMI patients compared with those in patients having other diagnoses (median 20.8 pmol/l vs. 6.0 pmol/l, p < 0.001). The combination of troponin T and copeptin at initial presentation resulted in an area under the receiver-operating characteristic curve of 0.97 (95% confidence interval: 0.95 to 0.98), which was significantly higher than the 0.86 (95% confidence interval: 0.80 to 0.92) for troponin T alone (p < 0.001). A copeptin level <14 pmol/l in combination with a troponin T  0.01 µg/l correctly ruled out AMI with a sensitivity of 98.8% and a negative predictive value of 99.7%.
Conclusions: The additional use of copeptin seems to allow a rapid and reliable rule out of AMI already at presentation and may thereby obviate the need for prolonged monitoring and serial blood sampling in the majority of patients. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE]; NCT00470587
[ClinicalTrials.gov]
)
Key Words: copeptin • rule out • acute myocardial infarction • troponin
|
Abbreviations and Acronyms
| | AMI = acute myocardial infarction | | AUC = area under the curve | | CI = confidence interval | | ECG = electrocardiography | | ED = emergency department | | ROC = receiver-operator characteristic |
|
Related Article
-
Inside This Issue
J. Am. Coll. Cardiol. 2009 54: A22.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
N. Schaub, T. Reichlin, R. Twerenbold, M. Reiter, S. Steuer, S. Bassetti, C. Stelzig, C. Wolf, K. Winkler, P. Haaf, et al.
Growth Differentiation Factor-15 in the Early Diagnosis and Risk Stratification of Patients with Acute Chest Pain
Clin. Chem.,
February 1, 2012;
58(2):
441 - 449.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. von Haehling, T. Stojakovic, and B. Bigalke
Copeptin--A Novel Marker in Acute Myocardial Infarction
Clin. Chem.,
January 1, 2012;
58(1):
307 - 309.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Karakas, J. L. Januzzi Jr., U. Hoffmann, and W. Koenig
In Reply
Clin. Chem.,
January 1, 2012;
58(1):
309 - 311.
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Schaub, T. Reichlin, C. Meune, R. Twerenbold, P. Haaf, W. Hochholzer, N. Niederhauser, P. Bosshard, C. Stelzig, M. Freese, et al.
Markers of Plaque Instability in the Early Diagnosis and Risk Stratification of Acute Myocardial Infarction
Clin. Chem.,
January 1, 2012;
58(1):
246 - 256.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Mueller
Counterpoint: Detection of Myocardial Infarction--Is It All Troponin? Role of New Markers
Clin. Chem.,
January 1, 2012;
58(1):
162 - 164.
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Giannitsis and H. A. Katus
Point: Detection of Myocardial Infarction--Is It All Troponin?
Clin. Chem.,
January 1, 2012;
58(1):
158 - 161.
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Keller, T. Zeller, F. Ojeda, S. Tzikas, L. Lillpopp, C. Sinning, P. Wild, S. Genth-Zotz, A. Warnholtz, E. Giannitsis, et al.
Serial Changes in Highly Sensitive Troponin I Assay and Early Diagnosis of Myocardial Infarction
JAMA,
December 28, 2011;
306(24):
2684 - 2693.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Authors/Task Force Members, C. W. Hamm, J.-P. Bassand, S. Agewall, J. Bax, E. Boersma, H. Bueno, P. Caso, D. Dudek, S. Gielen, et al.
ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC)
Eur. Heart J.,
December 1, 2011;
32(23):
2999 - 3054.
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Giannitsis, T. Kehayova, M. Vafaie, and H. A. Katus
Combined Testing of High-Sensitivity Troponin T and Copeptin on Presentation at Prespecified Cutoffs Improves Rapid Rule-Out of Non-ST-Segment Elevation Myocardial Infarction
Clin. Chem.,
October 1, 2011;
57(10):
1452 - 1455.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Karakas, J. L. Januzzi Jr., J. Meyer, H. Lee, C. L. Schlett, Q. A. Truong, W. Rottbauer, F. Bamberg, S. Dasdemir, U. Hoffmann, et al.
Copeptin Does Not Add Diagnostic Information to High-Sensitivity Troponin T in Low- to Intermediate-Risk Patients with Acute Chest Pain: Results from the Rule Out Myocardial Infarction by Computed Tomography (ROMICAT) Study
Clin. Chem.,
August 1, 2011;
57(8):
1137 - 1145.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Reichlin, A. Irfan, R. Twerenbold, M. Reiter, W. Hochholzer, H. Burkhalter, S. Bassetti, S. Steuer, K. Winkler, F. Peter, et al.
Utility of Absolute and Relative Changes in Cardiac Troponin Concentrations in the Early Diagnosis of Acute Myocardial Infarction
Circulation,
July 12, 2011;
124(2):
136 - 145.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Tentzeris, R. Jarai, S. Farhan, T. Perkmann, M. A. Schwarz, G. Jakl, J. Wojta, and K. Huber
Complementary role of copeptin and high-sensitivity troponin in predicting outcome in patients with stable chronic heart failure
Eur J Heart Fail,
July 1, 2011;
13(7):
726 - 733.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Benzing, S. Wellmann, F. Achini, J. Letzner, T. Burkhardt, E. Beinder, N. G. Morgenthaler, U. Haagen, H. U. Bucher, C. Buhrer, et al.
Plasma Copeptin in Preterm Infants: A Highly Sensitive Marker of Fetal and Neonatal Stress
J. Clin. Endocrinol. Metab.,
June 1, 2011;
96(6):
E982 - E985.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Balanescu, P. Kopp, M. B. Gaskill, N. G. Morgenthaler, C. Schindler, and J. Rutishauser
Correlation of Plasma Copeptin and Vasopressin Concentrations in Hypo-, Iso-, and Hyperosmolar States
J. Clin. Endocrinol. Metab.,
April 1, 2011;
96(4):
1046 - 1052.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Hochholzer, T. Reichlin, C. Stelzig, K. Hochholzer, J. Meissner, T. Breidthardt, M. Reiter, B. Duehsler, H. Freidank, K. Winkler, et al.
Impact of soluble fms-like tyrosine kinase-1 and placental growth factor serum levels for risk stratification and early diagnosis in patients with suspected acute myocardial infarction
Eur. Heart J.,
February 1, 2011;
32(3):
326 - 335.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. P. Giugliano and E. Braunwald
The Year in Non-ST-Segment Elevation Acute Coronary Syndrome
J. Am. Coll. Cardiol.,
December 14, 2010;
56(25):
2126 - 2138.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. S. Jaffe
Chapter 33 The use of biomarkers for acute cardiovascular disease
The ESC Textbook of Acute and Intensive Cardiac Care,
December 1, 2010;
1(1):
med-9780199584314-chapter - med-9780199584314-chapter.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Giannitsis and H. A. Katus
Chapter 34 Biomarkers in acute coronary syndromes
The ESC Textbook of Acute and Intensive Cardiac Care,
December 1, 2010;
1(1):
med-9780199584314-chapter - med-9780199584314-chapter.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. H. Darzy, K. C. Dixit, S. M. Shalet, N. G. Morgenthaler, and G. Brabant
Circadian Secretion Pattern of Copeptin, the C-Terminal Vasopressin Precursor Fragment
Clin. Chem.,
July 1, 2010;
56(7):
1190 - 1191.
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Enhorning, T. J. Wang, P. M. Nilsson, P. Almgren, B. Hedblad, G. Berglund, J. Struck, N. G. Morgenthaler, A. Bergmann, E. Lindholm, et al.
Plasma Copeptin and the Risk of Diabetes Mellitus
Circulation,
May 18, 2010;
121(19):
2102 - 2108.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Keller, S. Tzikas, T. Zeller, E. Czyz, L. Lillpopp, F. M. Ojeda, A. Roth, C. Bickel, S. Baldus, C. R. Sinning, et al.
Copeptin Improves Early Diagnosis of Acute Myocardial Infarction
J. Am. Coll. Cardiol.,
May 11, 2010;
55(19):
2096 - 2106.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. T. Maeder, D. Staub, M. H. Brutsche, N. Arenja, T. Socrates, M. Reiter, J. Meissner, N. G. Morgenthaler, A. Bergmann, J. Struck, et al.
Copeptin Response to Clinical Maximal Exercise Tests
Clin. Chem.,
April 1, 2010;
56(4):
674 - 676.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. N. DeMaria, J. J. Bax, O. Ben-Yehuda, G. K. Feld, B. H. Greenberg, J. Hall, M. Hlatky, W. Y.W. Lew, J. A.C. Lima, A. S. Maisel, et al.
Highlights of the Year in JACC 2009
J. Am. Coll. Cardiol.,
January 26, 2010;
55(4):
380 - 407.
[Full Text]
[PDF]
|
|
|
|
