Abstract
The aim of the study was to define new immune-inflammatory, oxidative stress and biochemical biomarkers, which predict mortality within a period of 3 months after acute ischemic stroke (AIS). We recruited 176 healthy volunteers and 145 AIS patients, categorized as AIS survivors and non-survivors, and measured interleukin (IL)-6, high sensitivity C-reactive protein (hsCRP), ferritin, iron, total serum protein (TSP), erythrocyte sedimentation rate (ESR), white blood cells (WBC), 25 hydroxyvitamin D [25(OH)D], lipid hydroperoxides (CL-LOOH), insulin, glucose and high-density lipoprotein (HDL)-cholesterol. In patients, these biomarkers were measured within 24 h after AIS onset. We also computed two composite scores reflecting inflammatory indices, namely INFLAM index1 (sum of z scores of hsCRP+IL-6 + ferritin+ESR + WBC) and INFLAM index2 (z INFLAM index1 – z 25(OH)D – z iron + z TSP). Three months after AIS, non-survivors (n = 54) showed higher baseline levels of IL-6, hsCRP, ferritin and glucose and lower levels of HDL-cholesterol and 25(OH)D than survivors (n = 91). Non-survivors showed higher baseline ESR and lowered TSP than controls, while survivors occupied an intermediate position. Death after AIS was best predicted by increased IL-6, glucose, ferritin and CL-LOOH and lowered 25(OH)D levels. The area under the receiver operating curves computed on the INFLAM index1 and 2 scores were 0.851 and 0.870, respectively. In conclusion, activation of peripheral immune-inflammatory, oxidative and biochemical pathways is critically associated with mortality after AIS. Our results may contribute to identify new biomarker sets, which may predict post-stroke death, as well as suggest that IL-6 trans-signaling coupled with redox imbalances may be possible new targets in the prevention of short-term outcome AIS death.
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Thanks to the Institutional Program for Scientific Initiation Scholarship (PIBIC) of the National Council for Scientific and Technological Development (CNPq); Clinical and Laboratory Pathophysiology Postgraduate Program, Health Sciences Center, State University of Londrina, Londrina, Paraná, Brazil; and Health Sciences Postgraduate Program, Health Sciences Center, State University of Londrina, Londrina, Paraná, Brazil.
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Study concept and design: EMVR and ANCS; acquisition of data: JRG, DFA, TF, MFL, MCMA; analysis and interpretation of data: EMVR, ANCS, MM; drafting of the manuscript: EMVR and MM; statistical analysis: MM; study supervision: EMVR, ERDA.
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Reiche, E.M.V., Gelinksi, J.R., Alfieri, D.F. et al. Immune-inflammatory, oxidative stress and biochemical biomarkers predict short-term acute ischemic stroke death. Metab Brain Dis 34, 789–804 (2019). https://doi.org/10.1007/s11011-019-00403-6
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DOI: https://doi.org/10.1007/s11011-019-00403-6