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April 02, 2013; 80 (14) Article

Copeptin adds prognostic information after ischemic stroke

Results from the CoRisk study

Gian Marco De Marchis, Mira Katan, Anja Weck, Felix Fluri, Christian Foerch, Oliver Findling, Philipp Schuetz, Daniela Buhl, Marwan El-Koussy, Henrik Gensicke, Marlen Seiler, Nils Morgenthaler, Heinrich P. Mattle, Beat Mueller, Mirjam Christ-Crain, Marcel Arnold
First published March 6, 2013, DOI: https://doi.org/10.1212/WNL.0b013e3182887944
Gian Marco De Marchis
From the Departments of Neurology, Neuroradiology, and Clinical Chemistry (G.M.D.M., A.W., O.F., D.B., M.E.-K., H.P.M., M.A.), Inselspital, University of Bern, Switzerland; Department of Neurology (G.M.D.M., M.K.), College of Physicians and Surgeons, Columbia University, New York, NY; Department of Neurology (M.K., F.F.), University Hospital of Zurich, Switzerland; Departments of Neurology and Endocrinology (M.K., F.F., H.G., M.C.-C.), University Hospital of Basel, Switzerland; Department of Neurology (C.F.), Goethe University, Frankfurt am Main, Germany; Medical University Clinic (P.S., B.M.), Cantonal Hospital Aarau, Switzerland; Thermo Fisher Scientific (M.S.), Hennigsdorf-Berlin, Germany; and Department of Experimental Endocrinology (N.M.), Charité, University Hospital Berlin, Germany.
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Mira Katan
From the Departments of Neurology, Neuroradiology, and Clinical Chemistry (G.M.D.M., A.W., O.F., D.B., M.E.-K., H.P.M., M.A.), Inselspital, University of Bern, Switzerland; Department of Neurology (G.M.D.M., M.K.), College of Physicians and Surgeons, Columbia University, New York, NY; Department of Neurology (M.K., F.F.), University Hospital of Zurich, Switzerland; Departments of Neurology and Endocrinology (M.K., F.F., H.G., M.C.-C.), University Hospital of Basel, Switzerland; Department of Neurology (C.F.), Goethe University, Frankfurt am Main, Germany; Medical University Clinic (P.S., B.M.), Cantonal Hospital Aarau, Switzerland; Thermo Fisher Scientific (M.S.), Hennigsdorf-Berlin, Germany; and Department of Experimental Endocrinology (N.M.), Charité, University Hospital Berlin, Germany.
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Anja Weck
From the Departments of Neurology, Neuroradiology, and Clinical Chemistry (G.M.D.M., A.W., O.F., D.B., M.E.-K., H.P.M., M.A.), Inselspital, University of Bern, Switzerland; Department of Neurology (G.M.D.M., M.K.), College of Physicians and Surgeons, Columbia University, New York, NY; Department of Neurology (M.K., F.F.), University Hospital of Zurich, Switzerland; Departments of Neurology and Endocrinology (M.K., F.F., H.G., M.C.-C.), University Hospital of Basel, Switzerland; Department of Neurology (C.F.), Goethe University, Frankfurt am Main, Germany; Medical University Clinic (P.S., B.M.), Cantonal Hospital Aarau, Switzerland; Thermo Fisher Scientific (M.S.), Hennigsdorf-Berlin, Germany; and Department of Experimental Endocrinology (N.M.), Charité, University Hospital Berlin, Germany.
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Felix Fluri
From the Departments of Neurology, Neuroradiology, and Clinical Chemistry (G.M.D.M., A.W., O.F., D.B., M.E.-K., H.P.M., M.A.), Inselspital, University of Bern, Switzerland; Department of Neurology (G.M.D.M., M.K.), College of Physicians and Surgeons, Columbia University, New York, NY; Department of Neurology (M.K., F.F.), University Hospital of Zurich, Switzerland; Departments of Neurology and Endocrinology (M.K., F.F., H.G., M.C.-C.), University Hospital of Basel, Switzerland; Department of Neurology (C.F.), Goethe University, Frankfurt am Main, Germany; Medical University Clinic (P.S., B.M.), Cantonal Hospital Aarau, Switzerland; Thermo Fisher Scientific (M.S.), Hennigsdorf-Berlin, Germany; and Department of Experimental Endocrinology (N.M.), Charité, University Hospital Berlin, Germany.
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Christian Foerch
From the Departments of Neurology, Neuroradiology, and Clinical Chemistry (G.M.D.M., A.W., O.F., D.B., M.E.-K., H.P.M., M.A.), Inselspital, University of Bern, Switzerland; Department of Neurology (G.M.D.M., M.K.), College of Physicians and Surgeons, Columbia University, New York, NY; Department of Neurology (M.K., F.F.), University Hospital of Zurich, Switzerland; Departments of Neurology and Endocrinology (M.K., F.F., H.G., M.C.-C.), University Hospital of Basel, Switzerland; Department of Neurology (C.F.), Goethe University, Frankfurt am Main, Germany; Medical University Clinic (P.S., B.M.), Cantonal Hospital Aarau, Switzerland; Thermo Fisher Scientific (M.S.), Hennigsdorf-Berlin, Germany; and Department of Experimental Endocrinology (N.M.), Charité, University Hospital Berlin, Germany.
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Oliver Findling
From the Departments of Neurology, Neuroradiology, and Clinical Chemistry (G.M.D.M., A.W., O.F., D.B., M.E.-K., H.P.M., M.A.), Inselspital, University of Bern, Switzerland; Department of Neurology (G.M.D.M., M.K.), College of Physicians and Surgeons, Columbia University, New York, NY; Department of Neurology (M.K., F.F.), University Hospital of Zurich, Switzerland; Departments of Neurology and Endocrinology (M.K., F.F., H.G., M.C.-C.), University Hospital of Basel, Switzerland; Department of Neurology (C.F.), Goethe University, Frankfurt am Main, Germany; Medical University Clinic (P.S., B.M.), Cantonal Hospital Aarau, Switzerland; Thermo Fisher Scientific (M.S.), Hennigsdorf-Berlin, Germany; and Department of Experimental Endocrinology (N.M.), Charité, University Hospital Berlin, Germany.
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Philipp Schuetz
From the Departments of Neurology, Neuroradiology, and Clinical Chemistry (G.M.D.M., A.W., O.F., D.B., M.E.-K., H.P.M., M.A.), Inselspital, University of Bern, Switzerland; Department of Neurology (G.M.D.M., M.K.), College of Physicians and Surgeons, Columbia University, New York, NY; Department of Neurology (M.K., F.F.), University Hospital of Zurich, Switzerland; Departments of Neurology and Endocrinology (M.K., F.F., H.G., M.C.-C.), University Hospital of Basel, Switzerland; Department of Neurology (C.F.), Goethe University, Frankfurt am Main, Germany; Medical University Clinic (P.S., B.M.), Cantonal Hospital Aarau, Switzerland; Thermo Fisher Scientific (M.S.), Hennigsdorf-Berlin, Germany; and Department of Experimental Endocrinology (N.M.), Charité, University Hospital Berlin, Germany.
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Daniela Buhl
From the Departments of Neurology, Neuroradiology, and Clinical Chemistry (G.M.D.M., A.W., O.F., D.B., M.E.-K., H.P.M., M.A.), Inselspital, University of Bern, Switzerland; Department of Neurology (G.M.D.M., M.K.), College of Physicians and Surgeons, Columbia University, New York, NY; Department of Neurology (M.K., F.F.), University Hospital of Zurich, Switzerland; Departments of Neurology and Endocrinology (M.K., F.F., H.G., M.C.-C.), University Hospital of Basel, Switzerland; Department of Neurology (C.F.), Goethe University, Frankfurt am Main, Germany; Medical University Clinic (P.S., B.M.), Cantonal Hospital Aarau, Switzerland; Thermo Fisher Scientific (M.S.), Hennigsdorf-Berlin, Germany; and Department of Experimental Endocrinology (N.M.), Charité, University Hospital Berlin, Germany.
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Marwan El-Koussy
From the Departments of Neurology, Neuroradiology, and Clinical Chemistry (G.M.D.M., A.W., O.F., D.B., M.E.-K., H.P.M., M.A.), Inselspital, University of Bern, Switzerland; Department of Neurology (G.M.D.M., M.K.), College of Physicians and Surgeons, Columbia University, New York, NY; Department of Neurology (M.K., F.F.), University Hospital of Zurich, Switzerland; Departments of Neurology and Endocrinology (M.K., F.F., H.G., M.C.-C.), University Hospital of Basel, Switzerland; Department of Neurology (C.F.), Goethe University, Frankfurt am Main, Germany; Medical University Clinic (P.S., B.M.), Cantonal Hospital Aarau, Switzerland; Thermo Fisher Scientific (M.S.), Hennigsdorf-Berlin, Germany; and Department of Experimental Endocrinology (N.M.), Charité, University Hospital Berlin, Germany.
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Henrik Gensicke
From the Departments of Neurology, Neuroradiology, and Clinical Chemistry (G.M.D.M., A.W., O.F., D.B., M.E.-K., H.P.M., M.A.), Inselspital, University of Bern, Switzerland; Department of Neurology (G.M.D.M., M.K.), College of Physicians and Surgeons, Columbia University, New York, NY; Department of Neurology (M.K., F.F.), University Hospital of Zurich, Switzerland; Departments of Neurology and Endocrinology (M.K., F.F., H.G., M.C.-C.), University Hospital of Basel, Switzerland; Department of Neurology (C.F.), Goethe University, Frankfurt am Main, Germany; Medical University Clinic (P.S., B.M.), Cantonal Hospital Aarau, Switzerland; Thermo Fisher Scientific (M.S.), Hennigsdorf-Berlin, Germany; and Department of Experimental Endocrinology (N.M.), Charité, University Hospital Berlin, Germany.
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Marlen Seiler
From the Departments of Neurology, Neuroradiology, and Clinical Chemistry (G.M.D.M., A.W., O.F., D.B., M.E.-K., H.P.M., M.A.), Inselspital, University of Bern, Switzerland; Department of Neurology (G.M.D.M., M.K.), College of Physicians and Surgeons, Columbia University, New York, NY; Department of Neurology (M.K., F.F.), University Hospital of Zurich, Switzerland; Departments of Neurology and Endocrinology (M.K., F.F., H.G., M.C.-C.), University Hospital of Basel, Switzerland; Department of Neurology (C.F.), Goethe University, Frankfurt am Main, Germany; Medical University Clinic (P.S., B.M.), Cantonal Hospital Aarau, Switzerland; Thermo Fisher Scientific (M.S.), Hennigsdorf-Berlin, Germany; and Department of Experimental Endocrinology (N.M.), Charité, University Hospital Berlin, Germany.
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Nils Morgenthaler
From the Departments of Neurology, Neuroradiology, and Clinical Chemistry (G.M.D.M., A.W., O.F., D.B., M.E.-K., H.P.M., M.A.), Inselspital, University of Bern, Switzerland; Department of Neurology (G.M.D.M., M.K.), College of Physicians and Surgeons, Columbia University, New York, NY; Department of Neurology (M.K., F.F.), University Hospital of Zurich, Switzerland; Departments of Neurology and Endocrinology (M.K., F.F., H.G., M.C.-C.), University Hospital of Basel, Switzerland; Department of Neurology (C.F.), Goethe University, Frankfurt am Main, Germany; Medical University Clinic (P.S., B.M.), Cantonal Hospital Aarau, Switzerland; Thermo Fisher Scientific (M.S.), Hennigsdorf-Berlin, Germany; and Department of Experimental Endocrinology (N.M.), Charité, University Hospital Berlin, Germany.
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Heinrich P. Mattle
From the Departments of Neurology, Neuroradiology, and Clinical Chemistry (G.M.D.M., A.W., O.F., D.B., M.E.-K., H.P.M., M.A.), Inselspital, University of Bern, Switzerland; Department of Neurology (G.M.D.M., M.K.), College of Physicians and Surgeons, Columbia University, New York, NY; Department of Neurology (M.K., F.F.), University Hospital of Zurich, Switzerland; Departments of Neurology and Endocrinology (M.K., F.F., H.G., M.C.-C.), University Hospital of Basel, Switzerland; Department of Neurology (C.F.), Goethe University, Frankfurt am Main, Germany; Medical University Clinic (P.S., B.M.), Cantonal Hospital Aarau, Switzerland; Thermo Fisher Scientific (M.S.), Hennigsdorf-Berlin, Germany; and Department of Experimental Endocrinology (N.M.), Charité, University Hospital Berlin, Germany.
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Beat Mueller
From the Departments of Neurology, Neuroradiology, and Clinical Chemistry (G.M.D.M., A.W., O.F., D.B., M.E.-K., H.P.M., M.A.), Inselspital, University of Bern, Switzerland; Department of Neurology (G.M.D.M., M.K.), College of Physicians and Surgeons, Columbia University, New York, NY; Department of Neurology (M.K., F.F.), University Hospital of Zurich, Switzerland; Departments of Neurology and Endocrinology (M.K., F.F., H.G., M.C.-C.), University Hospital of Basel, Switzerland; Department of Neurology (C.F.), Goethe University, Frankfurt am Main, Germany; Medical University Clinic (P.S., B.M.), Cantonal Hospital Aarau, Switzerland; Thermo Fisher Scientific (M.S.), Hennigsdorf-Berlin, Germany; and Department of Experimental Endocrinology (N.M.), Charité, University Hospital Berlin, Germany.
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Mirjam Christ-Crain
From the Departments of Neurology, Neuroradiology, and Clinical Chemistry (G.M.D.M., A.W., O.F., D.B., M.E.-K., H.P.M., M.A.), Inselspital, University of Bern, Switzerland; Department of Neurology (G.M.D.M., M.K.), College of Physicians and Surgeons, Columbia University, New York, NY; Department of Neurology (M.K., F.F.), University Hospital of Zurich, Switzerland; Departments of Neurology and Endocrinology (M.K., F.F., H.G., M.C.-C.), University Hospital of Basel, Switzerland; Department of Neurology (C.F.), Goethe University, Frankfurt am Main, Germany; Medical University Clinic (P.S., B.M.), Cantonal Hospital Aarau, Switzerland; Thermo Fisher Scientific (M.S.), Hennigsdorf-Berlin, Germany; and Department of Experimental Endocrinology (N.M.), Charité, University Hospital Berlin, Germany.
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Marcel Arnold
From the Departments of Neurology, Neuroradiology, and Clinical Chemistry (G.M.D.M., A.W., O.F., D.B., M.E.-K., H.P.M., M.A.), Inselspital, University of Bern, Switzerland; Department of Neurology (G.M.D.M., M.K.), College of Physicians and Surgeons, Columbia University, New York, NY; Department of Neurology (M.K., F.F.), University Hospital of Zurich, Switzerland; Departments of Neurology and Endocrinology (M.K., F.F., H.G., M.C.-C.), University Hospital of Basel, Switzerland; Department of Neurology (C.F.), Goethe University, Frankfurt am Main, Germany; Medical University Clinic (P.S., B.M.), Cantonal Hospital Aarau, Switzerland; Thermo Fisher Scientific (M.S.), Hennigsdorf-Berlin, Germany; and Department of Experimental Endocrinology (N.M.), Charité, University Hospital Berlin, Germany.
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Citation
Copeptin adds prognostic information after ischemic stroke
Results from the CoRisk study
Gian Marco De Marchis, Mira Katan, Anja Weck, Felix Fluri, Christian Foerch, Oliver Findling, Philipp Schuetz, Daniela Buhl, Marwan El-Koussy, Henrik Gensicke, Marlen Seiler, Nils Morgenthaler, Heinrich P. Mattle, Beat Mueller, Mirjam Christ-Crain, Marcel Arnold
Neurology Apr 2013, 80 (14) 1278-1286; DOI: 10.1212/WNL.0b013e3182887944

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Abstract

Objective: To evaluate and validate the incremental value of copeptin in the prediction of outcome and complications as compared with established clinical variables.

Methods: In this prospective, multicenter, cohort study, we measured copeptin in the emergency room within 24 hours from symptom onset in 783 patients with acute ischemic stroke. The 2 primary end points were unfavorable functional outcome (modified Rankin Scale score 3–6) and mortality within 90 days. Secondary end points were any of 5 prespecified complications during hospitalization.

Results: In multivariate analysis, higher copeptin independently predicted unfavorable outcome (adjusted odds ratio 2.17 for any 10-fold copeptin increase [95% confidence interval {CI}, 1.46–3.22], p < 0.001), mortality (adjusted hazard ratio 2.40 for any 10-fold copeptin increase [95% CI, 1.60–3.60], p < 0.001), and complications (adjusted odds ratio 1.93 for any 10-fold copeptin increase [95% CI, 1.33–2.80], p = 0.001). The discriminatory accuracy, calculated with the area under the receiver operating characteristic curve, improved significantly for all end points when adding copeptin to the NIH Stroke Scale score and the multivariate models. Moreover, the combination of copeptin with a validated score encompassing both the NIH Stroke Scale and age led to a net reclassification improvement of 11.8% for functional outcome and of 37.2% for mortality.

Conclusions: In patients with ischemic stroke, copeptin is a validated blood marker that adds predictive information for functional outcome and mortality at 3 months beyond stroke severity and age. Copeptin seems to be a promising new blood marker for prediction of in-hospital complications.

GLOSSARY

AUC=
area under the curve;
AVP=
arginine vasopressin;
CI=
confidence interval;
CRP=
C-reactive protein;
HR=
hazard ratio;
mRS=
modified Rankin Scale;
IQR=
interquartile range;
NIHSS=
NIH Stroke Scale;
NRI=
net reclassification improvement;
OR=
odds ratio;
ROC=
receiver operating characteristic

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at www.neurology.org

  • Editorial, page 1270

  • Received May 29, 2012.
  • Accepted November 9, 2012.
  • © 2013 American Academy of Neurology
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