High Serum Tissue Inhibitor of Matrix Metalloproteinase-1 Levels and Mortality in Patients with Spontaneous Intracerebral Hemorrhage

Abstract

Matrix metalloproteinase (MMP)-9, a member of the endoproteinase family, is involved in the neuroinflammation of spontaneous intracerebral hemorrhage (SIH). High circulating MMP-9 levels have been associated with poor functional outcome in patients with SIH. The objectives of this study were to determine whether serum MMP-9 and tissue inhibitor of matrix metalloproteinases (TIMP)-1 levels in SIH patients were higher in nonsurviving than surviving patients, if they were associated with early mortality, and if they could be used as biomarkers of prognosis. This observational prospective study included patients with severe supratentorial SIH (defined as Glasgow Coma Scale <9) from 6 Spanish Intensive Care Units. Serum MMP-9 and TIMP-1 levels were determined at the time of severe SIH diagnosis. Thirty-day mortality was the endpoint study. Nonsurviving patients (n= 46) showed higher serum TIMP-1 (P < 0.001) and MMP-9 levels (P= 0.01) than surviving patients (n= 54). The area under the curve by serum TIMP-1 levels for the prediction of 30-day mortality was 74% (95% confidence interval= 64%-82%; P<0.001). Multiple logistic regression analysis showed an association between serum TIMP-1 levels >223 ng/mL and 30-day mortality (odds ratio= 13.993; 95% confidence interval= 2.864-68.356; P= 0.001) after controlling for intracerebral hemorrhage score, glycemia, midline shift, and early evacuation of SIH. There was an association between circulating levels of TIMP-1 and MMP-9 (rho=0.25; P= 0.01). The novel aspects our study include that serum TIMP-1 and MMP-9 levels in SIH patients were higher in nonsurviving than in surviving patients and that serum TIMP-1 levels were associated with early mortality and could be used as biomarkers for predicting mortality.