title: Copeptin for risk stratification in non-traumatic headache in the emergency setting: a prospective multicenter observational cohort study.
abstract: BACKGROUND
  In the emergency setting, non-traumatic headache is a benign symptom in 80% of cases, but serious underlying conditions need to be ruled out. Copeptin improves risk stratification in several acute diseases. Herein, we investigated the value of copeptin to discriminate between serious secondary headache and benign headache forms in the emergency setting.
  
  
  METHODS
  Patients presenting with acute non-traumatic headache were prospectively enrolled into an observational cohort study. Copeptin was measured upon presentation to the emergency department. Primary endpoint was serious secondary headache defined by a neurologic cause requiring immediate treatment of the underlying disease. Secondary endpoint was the combination of mortality and hospitalization within 3 months. Two board-certified neurologist blinded to copeptin levels verified the endpoints after a structured 3-month-telephone interview.
  
  
  RESULTS
  Of the 391 patients included, 75 (19%) had a serious secondary headache. Copeptin was associated with serious secondary headache (OR 2.03, 95%CI 1.52-2.70, p < 0.0001). Area under the curve (AUC) for copeptin to identify the primary endpoint was 0.70 (0.63-0.76). After adjusting for age > 50, focal-neurological abnormalities, and thunderclap onset of symptoms, copeptin remained an independent predictive factor for serious secondary headache (OR 1.74, 95%CI 1.26-2.39, p = 0.001). Moreover, copeptin improved the AUC of the multivariate logistic clinical model (p-LR-test < 0.001). Even though copeptin values were higher in patients reaching the secondary endpoint, this association was not significant in multivariate logistic regression.
  
  
  CONCLUSIONS
  Copeptin was independently associated with serious secondary headache as compared to benign headaches forms. Copeptin may be a promising novel blood biomarker that should be further validated to rule out serious secondary headache in the emergency department.
  
  
  BACKGROUND
  Study Registration on 08/02/2010 as NCT01174901 at clinicaltrials.gov.
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, University Hospital Basel, Basel, Switzerland. claudineblum@yahoo.com.|Internal Medicine, Medical University Clinic, Kantonsspital Aarau, Tellstrasse, CH-5001, Aarau, Switzerland. claudineblum@yahoo.com.
authors.forename: Claudine Angela
authors.initials: CA
authors.lastname: Blum
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, University Hospital Basel, Basel, Switzerland.
authors.forename: Bettina
authors.initials: B
authors.lastname: Winzeler
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, University Hospital Basel, Basel, Switzerland.
authors.forename: Nicole
authors.initials: N
authors.lastname: Nigro
authors.affiliation: Internal Medicine, Medical University Clinic, Kantonsspital Aarau, Tellstrasse, CH-5001, Aarau, Switzerland.
authors.forename: Philipp
authors.initials: P
authors.lastname: Schuetz
authors.affiliation: Department of Neurology, Medical University Clinic, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Silke
authors.initials: S
authors.lastname: Biethahn
authors.affiliation: Department of Neurology, Medical University Clinic, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Timo
authors.initials: T
authors.lastname: Kahles
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, University Hospital Basel, Basel, Switzerland.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Mueller
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, University Hospital Basel, Basel, Switzerland.|Max-Planck-Institute for Metabolism Research, Cologne, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Timper
authors.affiliation: Department of Neurology, Medical University Clinic, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Katharina
authors.initials: K
authors.lastname: Haaf
authors.affiliation: Department of Neurology, Medical University Clinic, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Janina
authors.initials: J
authors.lastname: Tepperberg
authors.affiliation: Clinic of Neurology, University Hospital Basel, Basel, Switzerland.
authors.forename: Margareth
authors.initials: M
authors.lastname: Amort
authors.affiliation: Center of Laboratory Medicine, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Huber
authors.affiliation: Emergency Department, University Hospital Basel, Basel, Switzerland.
authors.forename: Roland
authors.initials: R
authors.lastname: Bingisser
authors.affiliation: Neurology, RehaClinic AG, Bad Zurzach, Switzerland.
authors.forename: Peter Stephan
authors.initials: PS
authors.lastname: Sándor
authors.affiliation: Department of Neurology, Medical University Clinic, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Krassen
authors.initials: K
authors.lastname: Nedeltchev
authors.affiliation: Internal Medicine, Medical University Clinic, Kantonsspital Aarau, Tellstrasse, CH-5001, Aarau, Switzerland.
authors.forename: Beat
authors.initials: B
authors.lastname: Müller
authors.affiliation: Clinic of Neurology, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Mira
authors.initials: M
authors.lastname: Katan
authors.affiliation: Division of Endocrinology, Department of Internal Medicine, University Hospital Basel, Basel, Switzerland.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Christ-Crain
mesh_terms: D000208:Acute Disease; D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D004636:Emergency Service, Hospital; D005260:Female; D005500:Follow-Up Studies; D006020:Glycopeptides / Q000097:blood*; D006261:Headache / Q000097:blood* / Q000175:diagnosis* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018570:Risk Assessment
chemical_list: D015415:Biomarkers; D006020:Glycopeptides; C048197:copeptins
keywords: Biomarker; Copeptin; Emergency; Head pain; Headache; Vasopressin