Immune-inflammatory, oxidative stress and biochemical biomarkers predict short-term acute ischemic stroke death

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.