title: Copeptin and Long-Term Risk of Recurrent Vascular Events After Transient Ischemic Attack and Ischemic Stroke: Population-Based Study.
abstract: OBJECTIVE
  Copeptin, the c-terminal portion of provasopressin, is a useful prognostic marker in patients after myocardial infarction and heart failure. More recently, high levels of copeptin have also been associated with worse functional outcome and increased mortality within the first year after ischemic stroke and transient ischemic attack (TIA). However, to date, there are no published data on whether copeptin predicts long-term risk of vascular events after TIA and stroke.
  
  
  METHODS
  We measured copeptin levels in consecutive patients with TIA or ischemic stroke in a population-based study (Oxford Vascular Study) recruited from 2002 to 2007 and followed up to 2014. Associations with risk of recurrent vascular events were determined by Cox-regression.
  
  
  RESULTS
  During ≈6000 patient-years in 1076 patients, there were 357 recurrent vascular events, including 174 ischemic strokes. After adjustment for age, sex, and risk factors, copeptin was predictive of recurrent vascular events (adjusted hazard ratio per SD, 1.47; 95% confidence interval, 1.31-1.64; P=0.0001), vascular death (1.85; 1.60-2.14; P<0.0001), all-cause death (1.75; 1.58-1.93; P<0.0001), and recurrent ischemic stroke (1.22; 1.04-1.44; P=0.017); and improved model-discrimination significantly: net reclassification improvement for recurrent vascular events (32%; P<0.0001), vascular death (55%; P<0.0001), death (66%; P<0.0001), and recurrent stroke (16%; P=0.044). The predictive value of copeptin was largest in patients with cardioembolic index events (adjusted hazard ratio, 1.84; 95% confidence interval, 1.53-2.20 versus 1.31, 1.14-1.50 in noncardioembolic stroke; P=0.0025). In patients with cardioembolic stroke, high copeptin levels were associated with a 4-fold increased risk of vascular events within the first year of follow-up (adjusted hazard ratio, 4.02; 95% confidence interval, 2.13-7.70).
  
  
  CONCLUSIONS
  In patients with TIA and ischemic stroke, copeptin predicted recurrent vascular events and death, particularly after cardioembolic TIA/stroke. Further validation is required, in particular, in studies using more extensive cardiac evaluation.
authors.affiliation: From the Centre for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neuroscience, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (S.G., H.C.S., A.I.B., D.L.P., Z.M., .M.R.); and Department of Neurology, Medical University of Vienna, Vienna, Austria (S.G.).
authors.forename: Stefan
authors.initials: S
authors.lastname: Greisenegger
authors.affiliation: From the Centre for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neuroscience, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (S.G., H.C.S., A.I.B., D.L.P., Z.M., .M.R.); and Department of Neurology, Medical University of Vienna, Vienna, Austria (S.G.).
authors.forename: Helen C
authors.initials: HC
authors.lastname: Segal
authors.affiliation: From the Centre for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neuroscience, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (S.G., H.C.S., A.I.B., D.L.P., Z.M., .M.R.); and Department of Neurology, Medical University of Vienna, Vienna, Austria (S.G.).
authors.forename: Annette I
authors.initials: AI
authors.lastname: Burgess
authors.affiliation: From the Centre for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neuroscience, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (S.G., H.C.S., A.I.B., D.L.P., Z.M., .M.R.); and Department of Neurology, Medical University of Vienna, Vienna, Austria (S.G.).
authors.forename: Debbie L
authors.initials: DL
authors.lastname: Poole
authors.affiliation: From the Centre for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neuroscience, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (S.G., H.C.S., A.I.B., D.L.P., Z.M., .M.R.); and Department of Neurology, Medical University of Vienna, Vienna, Austria (S.G.).
authors.forename: Ziyah
authors.initials: Z
authors.lastname: Mehta
authors.affiliation: From the Centre for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neuroscience, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom (S.G., H.C.S., A.I.B., D.L.P., Z.M., .M.R.); and Department of Neurology, Medical University of Vienna, Vienna, Austria (S.G.). peter.rothwell@ndcn.ox.ac.uk.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Rothwell
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002545:Brain Ischemia / Q000097:blood* / Q000175:diagnosis* / Q000453:epidemiology; D005260:Female; D006020:Glycopeptides / Q000097:blood*; D006801:Humans; D002546:Ischemic Attack, Transient / Q000097:blood* / Q000175:diagnosis* / Q000453:epidemiology; D008297:Male; D011159:Population Surveillance / Q000379:methods; D012008:Recurrence; D012307:Risk Factors; D020521:Stroke / Q000097:blood* / Q000175:diagnosis* / Q000453:epidemiology; D013997:Time Factors; D014652:Vascular Diseases / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D006020:Glycopeptides; C048197:copeptins
keywords: biomarkers; risk; stroke