Blood glutathione S-transferase-π as a time indicator of stroke onset

PLoS One. 2012;7(9):e43830. doi: 10.1371/journal.pone.0043830. Epub 2012 Sep 17.

Abstract

Background: Ability to accurately determine time of stroke onset remains challenging. We hypothesized that an early biomarker characterized by a rapid increase in blood after stroke onset may help defining better the time window during which an acute stroke patient may be candidate for intravenous thrombolysis or other intravascular procedures.

Methods: The blood level of 29 proteins was measured by immunoassays on a prospective cohort of stroke patients (N = 103) and controls (N = 132). Mann-Whitney U tests, ROC curves and diagnostic odds ratios were applied to evaluate their clinical performances.

Results: Among the 29 molecules tested, GST-π concentration was the most significantly elevated marker in the blood of stroke patients (p<0.001). More importantly, GST-π displayed the best area under the curve (AUC, 0.79) and the best diagnostic odds ratios (10.0) for discriminating early (N = 22, <3 h of stroke onset) vs. late stroke patients (N = 81, >3 h after onset). According to goal-oriented distinct cut-offs (sensitivity(Se)-oriented: 17.7 or specificity(Sp)-oriented: 65.2 ug/L), the GST-π test obtained 91%Se/50%Sp and 50%Se/91%Sp, respectively. Moreover, GST-π showed also the highest AUC (0.83) and performances for detecting patients treated with tPA (N = 12) compared to ineligible patients (N = 103).

Conclusions: This study demonstrates that GST-π can accurately predict the time of stroke onset in over 50% of early stroke patients. The GST-π test could therefore complement current guidelines for tPA administration and potentially increase the number of patients accessing thrombolysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Case-Control Studies
  • Female
  • Glutathione S-Transferase pi / blood*
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Stroke / blood*
  • Stroke / diagnosis*
  • Stroke / drug therapy
  • Time Factors
  • Tissue Plasminogen Activator / therapeutic use

Substances

  • Biomarkers
  • Glutathione S-Transferase pi
  • Tissue Plasminogen Activator

Grant support

Neurovascular Research Laboratory takes part in the Spanish stroke research network (RENEVAS, RD06/0026/0010) and the European Stroke Network (EUSTROKE 7FP Health F2-08-202213). This Swiss study was funded by Proteome Sciences plc. UNIGE has granted to Proteome Sciences the exclusive (worldwide) license to a patent protecting GSTP and NDKA as brain damage markers. The Spanish project was funded in part by a grant from the Fondo de Investigaciones Sanitarias (FIS PI08/361 and PI11/0176). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.