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BMC Neurology
Published in: BMC Neurology 1/2015

Open Access 01-12-2015 | Research article

Serum tissue inhibitor of matrix metalloproteinase-1 levels are associated with mortality in patients with malignant middle cerebral artery infarction

Authors: Leonardo Lorente, María M. Martín, Luis Ramos, Juan J. Cáceres, Jordi Solé-Violán, Mónica Argueso, Alejandro Jiménez, Juan M. Borreguero-León, Josune Orbe, José A. Rodríguez, José A. Páramo

Published in: BMC Neurology | Issue 1/2015

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Abstract

Background

In the last years, circulating matrix metalloproteinases (MMP)-9 levels have been associated with functional outcome in ischemic stroke patients. However the prognostic value of circulating levels of tissue inhibitor of matrix metalloproteinases (TIMP)-1 and MMP-10 in functional outcome of ischemic stroke patients has been scarcely studied. In addition, to our knowledge, serum MMP-9, MMP-10 and TIMP-1 levels in patients with malignant middle cerebral artery infarction (MMCAI) for mortality prediction have not been studied, and these were the objectives of this study.

Methods

This was a multicenter, observational and prospective study carried out in six Spanish Intensive Care Units. We included patients with severe MMCAI defined as Glasgow Coma Scale (GCS) lower than 9. We measured circulating levels of MMP-9, MMP-10, TIMP-1, in 50 patients with severe MMCAI at diagnosis and in 50 healthy subjects. Endpoint was 30-day mortality.

Results

Patients with severe MMCAI showed higher serum levels of MMP-9 (p = 0.001), MMP-10 (p < 0.001), and TIMP-1 (p = 0.02) than healthy subjects. Non-surviving MMCAI patients (n = 26) compared to survivor ones (n = 24) showed higher circulating levels of TIMP-1 (p < 0.001), MMP-10 (p = 0.02) and PAI-1(p = 0.02), and lower MMP-9 levels (p = 0.04). Multiple binomial logistic regression analysis showed that serum TIMP-1 levels > 239 ng/mL are associated with 30-day mortality (OR = 5.82; 95 % CI = 1.37-24.73; P = 0.02) controlling for GCS and age. The area under the curve for TIMP-1 as predictor of 30-day mortality was 0.81 (95 % CI = 0.67-0.91; P < 0.001). We found an association between circulating levels of TIMP-1 and MMP-10 (rho = 0.45; P = 0.001), plasminogen activator inhibitor (PAI)-1 (rho = 0.53; P < 0.001), and tumor necrosis factor (TNF)-alpha (rho = 0.70; P < 0.001).

Conclusions

The most relevant and new findings of our study, were that serum TIMP-1 levels in MMCAI patients were associated with mortality, and could be used as a prognostic biomarker of mortality in MMCAI patients.
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Metadata
Title
Serum tissue inhibitor of matrix metalloproteinase-1 levels are associated with mortality in patients with malignant middle cerebral artery infarction
Authors
Leonardo Lorente
María M. Martín
Luis Ramos
Juan J. Cáceres
Jordi Solé-Violán
Mónica Argueso
Alejandro Jiménez
Juan M. Borreguero-León
Josune Orbe
José A. Rodríguez
José A. Páramo
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2015
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-015-0364-7

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