Association between Serum Tissue Inhibitor of Matrix Metalloproteinase-1 Levels and Mortality in Patients with Severe Brain Trauma InjuryReportar como inadecuado




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Objective

Matrix 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.

Methods

This 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.

Results

Non-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; P<0.001. An association between TIMP-1 levels and APACHE-II score, TNF- alpha and TF was found.

Conclusions

The 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.



Autor: Leonardo Lorente , María M. Martín, Patricia López, Luis Ramos, José Blanquer, Juan J. Cáceres, Jordi Solé-Violán, Jorge S

Fuente: http://plos.srce.hr/



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