title: Biomarkers and mortality after transient ischemic attack and minor ischemic stroke: population-based study.
abstract: OBJECTIVE
  Premature death after transient ischemic attack or stroke is more often because of heart disease or cancer than stroke. Previous studies found blood biomarkers not usefully predictive of nonfatal stroke but possibly of all-cause death. This association might be explained by potentially treatable occult cardiac disease or cancer. We therefore aimed to validate the association of a panel of biomarkers with all-cause death, particularly cardiac death and cancer death, despite the absence of associations with risk of nonfatal vascular events.
  
  
  METHODS
  Fifteen biomarkers were measured in 929 consecutive patients in a population-based study (Oxford Vascular Study), recruited from 2002 and followed up to 2013. Associations were determined by Cox regression. Model discrimination was assessed by c-statistic and the integrated discrimination improvement.
  
  
  RESULTS
  During 5560 patient-years of follow-up, none of the biomarkers predicted risk of nonfatal vascular events. However, soluble tumor necrosis factor α receptor-1, von Willebrand factor, heart-type fatty-acid-binding protein, and N-terminal pro-B-type natriuretic peptide were independently predictive of all-cause death (n=361; adjusted hazard ratio per SD, 95% confidence interval: heart-type fatty-acid-binding protein: 1.31, 1.12-1.56, P=0.002; N-terminal pro-B-type natriuretic peptide: 1.34, 1.11-1.62, P=0.002; soluble tumor necrosis factor α receptor-1: 1.45, 1.26-1.66, P=0.02; von Willebrand factor: 1.19, 1.04-1.36, P=0.01). The independent contribution of the four biomarkers taken together added prognostic information and improved model discrimination (integrated discrimination improvement=0.028, P=0.0001). N-terminal pro-B-type natriuretic peptide was most predictive of vascular death (adjusted hazard ratio=1.80, 95% confidence interval, 1.34-2.41, P<0.0001), whereas heart-type fatty-acid-binding protein predicted cancer deaths (1.64, 1.26-2.12, P=0.0002). Associations were strongest in patients without known prior cardiac disease or cancer.
  
  
  CONCLUSIONS
  Several biomarkers predicted death of any cause after transient ischemic attack and minor stroke. N-terminal pro-B-type natriuretic peptide and heart-type fatty-acid-binding protein might improve patient selection for additional screening for occult cardiac disease or cancer, respectively. However, our results require validation in future studies.
authors: From the Stroke Prevention Research Unit, 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., P.M.R.); and Department of Neurology, Medical University of Vienna, Vienna, Austria (S.G.).
authors: Stefan
authors: S
authors: Greisenegger
authors: From the Stroke Prevention Research Unit, 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., P.M.R.); and Department of Neurology, Medical University of Vienna, Vienna, Austria (S.G.).
authors: Helen C
authors: HC
authors: Segal
authors: From the Stroke Prevention Research Unit, 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., P.M.R.); and Department of Neurology, Medical University of Vienna, Vienna, Austria (S.G.).
authors: Annette I
authors: AI
authors: Burgess
authors: From the Stroke Prevention Research Unit, 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., P.M.R.); and Department of Neurology, Medical University of Vienna, Vienna, Austria (S.G.).
authors: Debbie L
authors: DL
authors: Poole
authors: From the Stroke Prevention Research Unit, 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., P.M.R.); and Department of Neurology, Medical University of Vienna, Vienna, Austria (S.G.).
authors: Ziyah
authors: Z
authors: Mehta
authors: From the Stroke Prevention Research Unit, 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., P.M.R.); and Department of Neurology, Medical University of Vienna, Vienna, Austria (S.G.). peter.rothwell@ndcn.ox.ac.uk.
authors: Peter M
authors: PM
authors: Rothwell
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D050556:Fatty Acid-Binding Proteins / Q000097:blood; D005260:Female; D006801:Humans; D007249:Inflammation; D002546:Ischemic Attack, Transient / Q000097:blood* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000097:blood* / Q000401:mortality*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D015415:Biomarkers; D050556:Fatty Acid-Binding Proteins; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C109794:pro-brain natriuretic peptide (1-76); D014841:von Willebrand Factor; D020097:Natriuretic Peptide, Brain
keywords: biological markers; ischemic attack, transient; mortality; stroke
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