PLoS ONE (Jan 2014)

Association between serum tissue inhibitor of matrix metalloproteinase-1 levels and mortality in patients with severe brain trauma injury.

  • Leonardo Lorente,
  • María M Martín,
  • Patricia López,
  • Luis Ramos,
  • José Blanquer,
  • Juan J Cáceres,
  • Jordi Solé-Violán,
  • Jorge Solera,
  • Judith Cabrera,
  • Mónica Argueso,
  • Raquel Ortiz,
  • María L Mora,
  • Santiago Lubillo,
  • Alejandro Jiménez,
  • Juan M Borreguero-León,
  • Agustín González,
  • Josune Orbe,
  • José A Rodríguez,
  • José A Páramo

DOI
https://doi.org/10.1371/journal.pone.0094370
Journal volume & issue
Vol. 9, no. 4
p. e94370

Abstract

Read online

ObjectiveMatrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) play a role in neuroinflammation after brain trauma injury (TBI). Previous studies with small sample size have reported higher circulating MMP-2 and MMP-9 levels in patients with TBI, but no association between those levels and mortality. Thus, the aim of this study was to determine whether serum TIMP-1 and MMP-9 levels are associated with mortality in patients with severe TBI.MethodsThis was a multicenter, observational and prospective study carried out in six Spanish Intensive Care Units. Patients with severe TBI defined as Glasgow Coma Scale (GCS) lower than 9 were included, while those with Injury Severity Score (ISS) in non-cranial aspects higher than 9 were excluded. Serum levels of TIMP-1, MMP-9 and tumor necrosis factor (TNF)-alpha, and plasma levels of tissue factor (TF) and plasminogen activator inhibitor (PAI)-1 plasma were measured in 100 patients with severe TBI at admission. Endpoint was 30-day mortality.ResultsNon-surviving TBI patients (n = 27) showed higher serum TIMP-1 levels than survivor ones (n = 73). We did not find differences in MMP-9 serum levels. Logistic regression analysis showed that serum TIMP-1 levels were associated 30-day mortality (OR = 1.01; 95% CI = 1.001-1.013; P = 0.03). Survival analysis showed that patients with serum TIMP-1 higher than 220 ng/mL presented increased 30-day mortality than patients with lower levels (Chi-square = 5.50; P = 0.02). The area under the curve (AUC) for TIMP-1 as predictor of 30-day mortality was 0.73 (95% CI = 0.624-0.844; PConclusionsThe most relevant and new findings of our study, the largest series reporting data on TIMP-1 and MMP-9 levels in patients with severe TBI, were that serum TIMP-1 levels were associated with TBI mortality and could be used as a prognostic biomarker of mortality in TBI patients.