A panel of biomarkers including caspase-3 and d-dimer may differentiate acute stroke from stroke-mimicking conditions in the emergency department

J. Montaner, M. Mendioroz, M. Ribó, P. Delgado, M. Quintana, A. Penalba, P. Chacón, C. Molina, I. Fernández-Cadenas, A. Rosell, J. Alvarez-Sabín

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Abstract

Background and aims. 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. Design. Consecutive patients with strokes or stroke-mimicking conditions (mimics) were evaluated within 24h 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 >1.96ngmL-1 [odds ratio (OR)=3.32; 95% confidence interval (CI) 1.88-5.88, P<0.0001], d-dimer >0.27μgmL-1 (OR = 2.97; 95% CI 1.72-5.16, P=0.0001), sRAGE >0.91 ngmL-1 (OR=2.19; 95% CI 1.26-3.83, P=0.006), chimerin <1.11ngmL-1 (OR=0.4; 95% CI 0.19-0.81, P=0.011), secretagogin <0.24 ngmL-1 (OR=0.51; 95% CI 0.27-0.97, P=0.041) and MMP-9>199ngmL-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 3h 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. © 2010 The Association for the Publication of the Journal of Internal Medicine.
Original languageEnglish
Pages (from-to)166-174
JournalJournal of Internal Medicine
Volume270
Issue number2
DOIs
Publication statusPublished - 1 Aug 2011

Keywords

  • Biomarkers
  • Caspase-3
  • Cerebral ischaemia
  • d-dimer
  • Stroke

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    Montaner, J., Mendioroz, M., Ribó, M., Delgado, P., Quintana, M., Penalba, A., Chacón, P., Molina, C., Fernández-Cadenas, I., Rosell, A., & Alvarez-Sabín, J. (2011). A panel of biomarkers including caspase-3 and d-dimer may differentiate acute stroke from stroke-mimicking conditions in the emergency department. Journal of Internal Medicine, 270(2), 166-174. https://doi.org/10.1111/j.1365-2796.2010.02329.x