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

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.