Abstract 83: Hyperacute Matrix Metalloproteinase-2 Levels Predict Early Neurological Deterioration in Acute Ischemic Stroke

Abstract

Objectives: Clinical evolution after an acute ischemic stroke can be variable and patients may experience early neurological improvement (ENI) or early neurological deterioration (END). It is still unclear if inflammation, MMPs and oxidative stress, as mediators of brain damage, might be also responsible for the neurological impairment during the acute stage of an ischemic stroke. Using data from a prospective, hospital-based cohort of AIS patients, we sought to establish whether the baseline levels of these biomarkers correlate with and predict these different clinical courses. Methods: We prospectively measured hs-CRP, MMP-2 and MMP-9 (analyzed using an ELISA assay), F2 isoprostane (F2isoP), urinary 8-hydroxydeoxyguanosine (8OHdG), the Oxygen Radical Absorbance Capacity Assay (ORAC) on consecutive acute stroke patients (<9 hours from symptom onset) in a multicenter acute ischemic stroke biomarker study. Clinical and demographic data including NIHSS scores at baseline, 48 hours, and discharge, stroke subtype, imaging, and 3 month mRS were collected. Patients with acute infection, active malignancy, or systemic inflammatory disorder were excluded. END was defined as a worsening of presenting symptom with an increase ≥4 points NIHSS at 48 hours or death at 48 hours. Multivariate logistic regression model was used to adjust for the effects of potential confounding variables. Results: Of 528 subjects enrolled in the study we included 132 patients, mean age 71.8 (s.d. 13.8), 48.5% female, 56.1% treated with t-PA in the analysis of which 33 (25%) had END. In univariate analyses, age (76.8±11.1 vs 70.1±14.3; p=0.015), diabetes mellitus (36.4% vs 18.2%, p=0.05), chronic renal failure (18.2% vs 3.0%, p=0.003), systolic blood pressure (164.2±34.5; p=0.05), creatinine (1.3±0.5 vs 1.1±0.3 mg/dl; p=0.025), infarct growth (54.6% vs 48.5%; p=0.06) and baseline MMP-2 (407.9±166.9 vs 332.4±133.9; p=0.013), were associated with END. Baseline NIHSS was significantly lower in patients with END (9.2±5.4 vs 12.3±5.9; p=0.009). At 48 hours MMP-2 levels decreased both in patients with END and ENI (p=0.11). After adjustment for all the confounding variables, MMP-2 remained an independent predictor of END (OR 1.005, 95%CI 1.001-1.009, p=0.013). Conclusions: High hyperacute levels of MMP-2 independently predict END in acute ischemic stroke patients. Hence, high baseline MMP-2 levels might play an active role in determining brain injury in the acute phase and can become a valuable specific surrogate marker of stroke progression.