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London, United Kingdom 2013 12 Etiology of stroke and risk factors B 16:50 - 17:00 Inflammatory markers and metalloproteinases profiles predict death in ischemic stroke patients treated with tPA thrombolysis. A.M. Gori1, M. Nesi2, B. Giusti3, V. Palumbo4, A. Armillis5, B. Piccardi6, P. Nencini7, G. Pra-cucci8, G.F. Gensini9, R. Abbate10, D. Inzitari11 Dept. Experimental and Clinical Medicine, University of Florence, Florence, ITALY1,D-ept. of Stroke Unit and Neurology, Careggi University Hospital, Florence, ITALY2, Dept. Ex-perimental and Clinical Medicine, University of Florence, Florence, ITALY3, Dept. Of Stroke Unit and Neurology, Careggi University Hospital, Florence, ITALY4, Dept. Experimental and Clinical Medicine, University of Florence, Florence, ITALY5, Dept. Of Stroke Unit and Neu-rology, Careggi University Hospital, Florence, ITALY6, Dept. Of Stroke Unit and Neurology, Careggi University Hospital, Florence, ITALY7, Dept. Of Stroke Unit and Neurology, Careggi University Hospital, Florence, ITALY8, Dept. Experimental and Clinical Medicine, University of Florence, Florence, ITALY9, Dept. Experimental and Clinical Medicine, University of Florence, Florence, ITALY10, Dept. Of Stroke Unit and Neurology, Careggi University Hospital, Florence, ITALY11 Background: Inflammatory mediators and metalloproteinases(MMPs) are altered in the acute phase of ischemic stroke and play a detrimental role on severity and hemorrhagic transforma-tion of ischemic brain lesions after thrombolysis. This study aimed to evaluate the effect of in-flammatory and MMPs profiles(table) on mortality in stroke patients submitted to thrombolysis. Methods: Blood was taken at baseline and 24 hours after thrombolysis from 327 patients (mean age 68, mean NIHSS 11.9) with acute ischemic stroke. Circulating molecules were measured using Bio-plex suspension array system(table). Baseline values and delta median values (post tPA-baseline)/baseline of each parameters were analyzed in 3 month-survivors and non-survi-vors. Cerebrovasc Dis 2013; 35 (suppl 3)1-854 73 Results: Baseline levels of C-reactive Protein, haptoglobin, alpha2-macroglobulin(A2M), in-terleukin( IL)-10 (IL-10), IL-12 and IL-6 and delta values of MMPs 1,8,9 and TIMP1 were sig-nificantly different in patients who died with respect to survivors(table). Adjusting for age, sex, glycemia, baseline NIHSS, history of atrial fibrillation, or congestive heart failure, history of in-flammatory diseases or infections occurred within the last 7 days before stroke onset, only del-taMMP9 and baseline A2M remained significantly and independently associated with 3 month-death OR (95% CI):baseline A2M:1.49(1.12-2.00);deltaMMP9:1.58(1.11-2.26), p<0.01. ROC analysis demonstrated that the addition of baseline A2M and deltaMMP9 (model 2) to a model that included factors known to affect the outcome(model 1) significantly improved the area under the curve for the detection of mortality in ischemic stroke patients 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. Conclusion: our findings suggest that A2M and deltaMMP9 are significant and independent markers of mortality and that may be used to improve prediction of unfavourable outcome in the clinical setting of ischaemic stroke patients treated with thrombolytic therapy. Biomarker All patients HR (95% CI) p TIA HR (95% CI) p Minor Stroke HR (95% CI) p Major Stroke HR (95% CI) P Fibrinogen 1.04(0.98- 1.11) 0.176 1.00(0.88-1.13) 0.983 1.02(0.93-1.12) 0.642 1.10(0.96- 1.26) 0.167 Protein Z (PZ) 0.97(0.91- 1.03) 0.258 1.04(0.93-1.18) 0.477 0.97(0.89-1.06) 0.552 0.93(0.82- 1.05) 0.247 D-dimer 1.06(0.99- 1.14) 0.070 1.16(1.02-1.33) 0.026 1.03(0.94-1.14) 0.520 0.96(0.83- 1.10) 0.534 Von Willebrand Fac-tor 1.01(0.95- 1.08) 0.659 1.00(0.88-1.14) 0.980 0.97(0.88-1.06) 0.481 1.06(0.92- 1.21) 0.414 P-selectin 1.05(0.99- 1.11) 0.121 1.00(0.89-1.13) 0.963 1.02(0.93-1.11) 0.716 1.10(0.97- 1.24) 0.137 Thrombomodulin 1.00(0.94- 1.06) 0.951 0.99(0.88-1.11) 0.837 1.02(0.94-1.11) 0.680 1.00(0.90- 1.12) 0.985 Brain Derived Neu-rotrophic Factor 1.02(0.96- 1.08) 0.543 1.00(0.88-1.13) 0.938 0.98(0.91-1.06) 0.624 1.06(0.94- 1.20) 0.326 C Reactive Protein 1.08(1.01- 1.16) 0.025 1.01(0.88-1.15) 0.935 1.08(0.98-1.19) 0.288 1.20(0.99- 1.44) 0.056 Interleukin-6 1.08(1.02- 1.15) 0.010 0.99(0.87-1.12) 0.854 1.06(0.97-1.16) 0.177 1.22(1.04- 1.42) 0.012 Tumour Necrosis Factor-1 1.01(0.95- 1.08) 0.664 0.95(0.84-1.07) 0.368 1.05(0.96-1.14) 0.286 0.96(0.85- 1.09) 0.544 Heart Fatty Acid bin-ding Protein 1.06(1.00- 1.14) 0.069 0.94(0.82-1.09) 0.421 1.07(0.97-1.18) 0.156 1.11(0.97- 1.28) 0.124 Neurone Specific Enolase 1.01(0.95- 1.07) 0.743 0.99(0.88-1.12) 0.923 0.99(0.91-1.07) 0.791 1.00(0.89- 1.13) 0.990 NGAL 1.05(0.99- 1.12) 0.126 0.99(0.87-1.13) 0.907 1.06(0.97-1.16) 0.214 1.00(0.88- 1.14) 0.945 Anti- phoshorylcho-line 1.00(0.93- 1.06) 0.902 1.01(0.99-1.15) 0.935 0.93(0.84-1.02) 0.125 1.11(0.95- 1.29) 0.193 Table 1A: Risk of recurrent stroke within five years (HR per decile increase in level) for 14 biomarker in patients presenting with TIA, minor ischaemic stroke (NIHSS≤3) and major isch-aemic stroke. Hazard Ratio (95% Confidence Intervals) are adjusted for age and sex. NGAL= Neutrophil gelatinase associated lipocalin Biomarker All patients HR (95% CI) p TIA HR (95% CI) p Minor Stroke HR (95% CI) p Major Stroke HR (95% CI) P Fibrinogen 0.97(0.97-1.01) 0.578 0.99(0.81- 1.20) 0.891 0.91(0.77-1.09) 0.327 1.08(0.82-1.42) 0.596 Protein Z 0.92(0.82-1.03) 0.155 0.81(0.67- 0.98) 0.031 0.96(0.81-1.14) 0.659 1.08(0.82-1.42) 0.590 D-dimer 1.03(0.92-1.16) 0.616 1.02(0.84- 1.25) 0.815 1.03(0.85-1.24) 0.784 1.08(0.83-1.41) 0.594 Von Willebrand Factor 0.94(0.84-1.05) 0.272 0.87(0.70- 1.07) 0.172 0.96(0.81-1.15) 0.658 1.05(0.79-1.39) 0.743 P-selectin 1.02(0.92-1.14) 0.700 0.90(0.75- 1.09) 0.287 1.04(0.88-1.23) 0.624 1.21(0.93-1.59) 0.158 Thrombomodulin 0.98(0.87-1.10) 0.712 1.14(0.93- 1.40) 0.218 0.90(0.74-1.08) 0.245 0.92(0.73-1.16) 0.466 Brain Derived Neu-rotrophic Factor 1.03(0.92-1.14) 0.647 0.94(0.76- 1.16) 0.554 1.04(0.88-1.23) 0.647 1.14(0.89-1.50) 0.357 C Reactive Protein 0.93(0.82-1.06) 0.261 1.05(0.84- 1.31) 0.673 0.85(0.69-1.05) 0.142 0.87(0.67-1.12) 0.283 Interleukin-6 1.17(1.04-1.32) 0.011 1.15(0.94- 1.41) 0.179 1.22(1.01-1.48) 0.041 1.21(0.87-1.68) 0.249 Tumour Necrosis Fac-tor- 1 0.99(0.88-1.11) 0.812 0.97(0.79- 1.19) 0.764 0.99(0.82-1.19) 0.901 0.98(0.76-1.27) 0.892 Heart Fatty Acid bin-ding Protein 1.12(0.98-1.28) 0.086 0.95(0.76- 1.20) 0.686 1.30(1.03-1.63) 0.025 1.19(0.88-1.62) 0.262 Neurone Specific Eno-lase 1.01(0.90-1.13) 0.841 0.99(0.82- 1.21) 0.940 1.08(0.90-1.29) 0.419 0.91(0.72-1.16) 0.444 NGAL 1.14(1.00-1.29) 0.049 1.07(0.87- 1.32) 0.501 1.16(0.94-1.11) 0.156 1.22(0.87-1.72) 0.251 Anti- phoshorylcholine 1.01(0.90-1.13) 0.903 1.05(0.84- 1.31) 0.673 0.96(0.81-1.14) 0.656 1.26(0.93-1.70) 0.136 Table 1B: Risk of Myocardial Infarction within five years (HR per decile increase in level), for 14 biomarker in patients presenting with TIA, minor ischaemic stroke (NIHSS≤3) and ma-jor ischaemic stroke. Hazard Ratio (95% Confidence Intervals) are adjusted for age and sex. NGAL= Neutrophil gelatinase associated lipocalin


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