High serum levels of tissue inhibitor of matrix metalloproteinase-1 during the first week of a malignant middle cerebral artery infarction in non-surviving patients

BMC Neurol. 2019 Jul 18;19(1):167. doi: 10.1186/s12883-019-1401-8.

Abstract

Background: Higher circulating levels of tissue inhibitor of matrix metalloproteinases (TIMP)-1 early after ischemic stroke have been associated with lower survival. The objectives of this study were to determine serum TIMP-1 levels during the first week of a severe cerebral infarction in surviving and non-surviving patients, and whether those levels during the first week could be used as a mortality biomarker for these patients.

Methods: We included patients with severe malignant middle cerebral artery infarction (MMCAI) defined as computer tomography showing ischaemic changes in more than 50% of the middle cerebral artery territory and Glasgow Coma Scale (GCS) ≤ 8. We measured serum levels of matrix metalloproteinases (MMP)-9 and TIMP-1. End-point study was 30-day mortality.

Results: We found higher TIMP-1 concentrations at days 1 (p < 0.001), 4 (p = 0.001), and 8 (p = 0.03) of MMCAI in non- urviving (n = 34) than in surviving (n = 34) patients. We found lower serum MMP-9 concentrations at day 1 (p = 0.03) of MMCAI and no significant differences at days 4 and 8. ROC curve analysis of TIMP-1 concentrations performed at days 1, 4, and 8 of MMCAI showed an area under curve to predict 30-day mortality of 81% (p < 0.001), 80% (p < 0.001) and 72% (p = 0.07) respectively.

Conclusions: The new findings of our study were that non-surviving MMCAI patients showed higher serum TIMP-1 levels during the first week of MMCAI that surviving patients, and those levels during the first week of MMCAI could be used as mortality biomarkers.

Keywords: Ischemic stroke; Mortality; Patients; Prognosis; TIMP-1.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Biomarkers / blood
  • Female
  • Glasgow Coma Scale
  • Humans
  • Infarction, Middle Cerebral Artery / blood*
  • Infarction, Middle Cerebral Artery / mortality
  • Male
  • Matrix Metalloproteinase 9 / blood
  • Middle Aged
  • Prospective Studies
  • ROC Curve
  • Stroke / blood
  • Tissue Inhibitor of Metalloproteinase-1 / blood*

Substances

  • Biomarkers
  • TIMP1 protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • Matrix Metalloproteinase 9