title: A panel of biomarkers including caspase-3 and D-dimer may differentiate acute stroke from stroke-mimicking conditions in the emergency department.
abstract: OBJECTIVE
  At present, a rapid and widely available diagnostic test for stroke remains elusive. The aim of this study was to examine the predictive value of a panel of blood-borne biochemical markers for stroke diagnosis.
  
  
  METHODS
  Consecutive patients with strokes or stroke-mimicking conditions (mimics) were evaluated within 24 h from symptom onset (915 strokes and 90 mimics). Blood samples were analysed by enzyme-linked immunosorbent assay for C-reactive protein, d-dimer, soluble receptor for advanced glycation end products (sRAGE), metalloproteinase 9 (MMP-9), S100B, brain natriuretic peptide, caspase-3, neurotrophin-3, chimerin and secretagogin.
  
  
  RESULTS
  The main independent predictors of stroke versus mimics were caspase-3 >1.96 ng mL(-1) [odds ratio (OR) = 3.32; 95% confidence interval (CI) 1.88-5.88, P < 0.0001], d-dimer >0.27 μg mL(-1) (OR = 2.97; 95% CI 1.72-5.16, P = 0.0001), sRAGE >0.91 ng mL(-1) (OR = 2.19; 95% CI 1.26-3.83, P = 0.006), chimerin <1.11 ng mL(-1) (OR = 0.4; 95% CI 0.19-0.81, P = 0.011), secretagogin <0.24 ng mL(-1) (OR = 0.51; 95% CI 0.27-0.97, P = 0.041) and MMP-9 > 199 ng mL(-1) (OR = 1.66; 95% CI 1.01-2.73, P = 0.046). The model's predictive probability of stroke when the six biomarkers are above/below these cut-off levels was 99.01%. The best combination of biomarkers in the model was caspase-3 and d-dimer. Moreover, a model developed for samples obtained within the first 3 h showed high sensitivity (Se) and specificity (Sp) (threshold at 25th percentile: Se 0.87, Sp 0.55; threshold at 75th percentile: Se 0.28, Sp 0.99).
  
  
  CONCLUSIONS
  A combination of biomarkers including caspase-3 and d-dimer appears to be the most promising to achieve a rapid biochemical diagnosis of stroke. If replicated, this approach could be used as a tool for urgent referral of stroke patients to hospitals in which acute treatments are available.
authors.affiliation: Neurovascular Research Laboratory, Universitat Autònoma de Barcelona, Vall d'Hebron Hospital, Barcelona, Spain. 31862jmv@comb.cat
authors.forename: J
authors.initials: J
authors.lastname: Montaner
authors.forename: M
authors.initials: M
authors.lastname: Mendioroz
authors.forename: M
authors.initials: M
authors.lastname: Ribó
authors.forename: P
authors.initials: P
authors.lastname: Delgado
authors.forename: M
authors.initials: M
authors.lastname: Quintana
authors.forename: A
authors.initials: A
authors.lastname: Penalba
authors.forename: P
authors.initials: P
authors.lastname: Chacón
authors.forename: C
authors.initials: C
authors.lastname: Molina
authors.forename: I
authors.initials: I
authors.lastname: Fernández-Cadenas
authors.forename: A
authors.initials: A
authors.lastname: Rosell
authors.forename: J
authors.initials: J
authors.lastname: Alvarez-Sabín
mesh_terms: D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D053148:Caspase 3 / Q000097:blood*; D020740:Chimerin Proteins / Q000097:blood; D003937:Diagnosis, Differential; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis*; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009414:Nerve Growth Factors / Q000097:blood; D020933:Neurotrophin 3 / Q000097:blood; D011237:Predictive Value of Tests; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood; D020521:Stroke / Q000097:blood / Q000175:diagnosis*
chemical_list: D015415:Biomarkers; D020740:Chimerin Proteins; D005338:Fibrin Fibrinogen Degradation Products; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; C036309:fibrin fragment D; D020097:Natriuretic Peptide, Brain; D002097:C-Reactive Protein; D053148:Caspase 3; D020780:Matrix Metalloproteinase 9