Abstract T P59: Inflammatory Mediators and Metalloproteinase Profile Predict Poor Outcome in Ischemic Stroke Patients Treated with Thrombolysis: Results from the MAGIC Study

Background: Experimentally inflammatory mediators and metalloproteinases (MMPs) play a detrimental role related to severity of an ischemic brain lesion. MMPs activity is also induced by the inflammatory response after an ischemic attack. This study aimed to evaluate the role of a large panel of circulating molecules in the setting of tPA treated stroke patients Methods: Blood was taken before and 24-hours after tPA from 327 patients (mean age 68 years, median NIHSS 11) with acute ischemic stroke. Baseline values and delta median values [(post tPA-baseline)/baseline] of each parameters were analyzed related to 3-month death and 3-month Rankin scale (mRs) score 3-6. The net effect of each biomarker was estimated by a logistic regression model including the major clinical determinants. Results: 1) Death vs survival: significant for baseline alpha 2-macroglobulin (A2M), deltaMMP9, and deltaTIMP1 [OR (95%CI): A2M 2.52(1.14-5.55); MMP9 1.58(1.11-2.26), TIMP1 2.59(1.44 - 4.66)]. 2) mRs 3-6 vs 0-2: significant for deltaMMP9, deltaIL6, and deltaCRP [OR (95%CI): MMP9 1.35(1.01 - 1.81); IL6 1.07(1.01-1.13); CRP 1.03(1.01-1.06)]. ROC analysis demonstrated that the addition of baseline A2M and deltaMMP9 (model 2) to a model including factors known to affect the outcome (model 1) significantly improved the area under the curve for mortality [model 1: AUC=0.82 (95%CI 0.75-0.90); model 2: AUC=0.88 (95%CI 0.83-0.93), p<0.05]. Discussion: Our data add substantial clinical evidence about the detrimental role of inflammatory mediators and MMPs profile, in particular A2M and MMP9, in tPA treated stroke patients.