Correlation Of Apolipoprotein ε4 With Perihematoma Edema And Short-term Prognosis In Patients With Intracerebral Hemorrhage

Objective:Part Ⅰ: Comparison of indicators of inflammation between patients carrying the ApoEε3 gene and ApoEε4 gene for intracerebral hemorrhage(ICH)and analysis of the impact on patient prognosis at hospital discharge;Part II: Comparison of the severity of perihematomal edema(PHE)volume in patients carrying the ApoEε3 gene with those carrying the ApoEε4 genotype for ICH and analysis of the impact on patient prognosis at hospital discharge;Part Ⅲ: To observe the pattern of changes in PHE volume with inflammatory indicators after the onset of ICH and to explore the mechanisms involved in the Cyp A/NF-κB/MMP-9 pathway through the patients’ cerebrospinal fluid.Methods:Part Ⅰ: Comparison of inflammatory indicators between patients with ICH carrying ApoEε3 and ApoEε4 genes and the impact on short-term prognosis: Patients with ICH and ApoE gene test results were retrospectively collected from January 2020 to February 2023 at the Department of Emergency Neurology of the Affiliated Hospital of Guizhou Medical University,and were first divided into ApoEε3 and ApoEε4groups based on ApoE gene test results.The demographics,baseline clinical data,peripheral blood tests,haematoma volume,National Institute of Health stroke scale(NIHSS)score and Glasgow coma scale(GCS)score were compared between the two groups.(GCS)scores were compared and analysed.The group was then divided into good prognosis(m RS ≤ 3)and poor prognosis(m RS > 3)according to the Modified Rankin Scale(m RS)scores at the time of discharge.The effect of various laboratory tests and haematoma volume on the prognosis of the patients was investigated by univariate analysis,and independent risk factors for poor prognosis were identified and ROC curves were plotted using binary logistic regression analysis.Part Ⅱ: Comparison of the severity of PHE volumes in patients carrying ApoEε3and ApoEε4 genotypes of ICH: A total of 205 patients were included in the first part of ICH patients,adjusted for the range of haematoma volumes and excluded the effect of haematoma volumes on prognosis for comparison.PHE volumes were calculated using the Tada formula and 3D Slicer software,respectively,and then the sum of the PHE volumes obtained from the two measurements was averaged for comparison between the two groups of ApoEε3 and ApoEε4 for the three PHE volumes.Baseline characteristics,complications and remaining imaging features were also compared between the ApoEε3 and ApoEε4 groups.The PHE volumes and associated imaging features were again analysed interprognostically,using binary logistic regression analysis,to find independent risk factors for poor patient prognosis and to plot ROC curves.Part Ⅲ: Inflammatory indicators,haematoma volume and PHE volume of all patients in Part 1 were included,and Pearson correlation analysis was applied to observe the pattern of change in PHE volume with haematoma and inflammation level after the onset of ICH.The test was attempted by collecting cerebrospinal fluid specimens from patients: patients with cerebral haemorrhage and acute obstructive hydrocephalus who required drainage of cerebrospinal fluid outside the body were collected,and waste cerebrospinal fluid was collected from patients’ lateral ventricular drains on days 1,3 and 5 of the onset,respectively,and Cyp A,NF-κB and MMP-9indexes in cerebrospinal fluid were detected by ELISA,and the relevant indexes were compared between the two groups of ApoEε3 and ApoEε4 The differences between the two groups were compared.Results:Part Ⅰ: A total of 257 patients with ICH and with ApoE gene test results admitted to the emergency neurology department of the Affiliated Hospital of Guizhou Medical University from January 2020 to February 2023 were included.Comparing the two groups of patients with ICH carrying ApoEε3 and ApoEε4 genes,the results suggested that the differences were statistically significant between the two groups in brain herniation,admission GCS,admission NHISS,white blood cell count,absolute neutrophil value,absolute lymphocyte value,mean red blood cell volume,mean red blood cell haemoglobin volume in blood routine at admission,and potassium and calcium in electrolytes.There were statistically significant differences in haematoma volume,haemorrhage breaking into the ventricles,brain herniation,ApoEε4,white blood cell count,absolute neutrophil values,magnesium,carbon dioxide binding capacity,anion gap,glutamate/glutamate,gamma-glutamyl transpeptidase,cholinesterase and pre-albumin in the two groups with a good and poor prognosis.Binary logistic regression of single factors affecting prognosis showed that haematoma volume,ApoEε4,white blood cell count,absolute neutrophil value,and pre-albumin were independent risk factors for poor prognosis in patients with ICH(P< 0.05).ROC curves were plotted to assess the predictive value of ApoEε4,white blood cell count,absolute neutrophil value,and haematoma volume within 24 h of onset on the prognosis of patients with ICH.Using 0.50 as the reference value for the area under the ROC curve,the sensitivity,specificity,positive and negative predictive values for ApoEε4 to predict poor prognosis in patients were 0.457,0.83,0.26 and0.68,respectively.The Jorden index was 0.287,corresponding to an AUC of 0.646(P(27)0.001).The leukocyte count AUC was 0.599(95% CI: 0.525 to 0.673,P = 0.007),corresponding to a sensitivity of 39% and specificity of 84.4% when the cut-off value for the onset leukocyte count was 11.245,with a Jordon index of 0.234.The absolute neutrophil AUC was 0.577(95% CI: 0.503 to 0.652,P =0.036),corresponding to a sensitivity of 37.1% and specificity of 84.4% at an absolute neutrophil cut-off value of 9.6 and a Jorden index of 0.215.The AUC for haematoma volume was 0.668(95%CI:0.602-0.735,P(27)0.001),corresponding to a sensitivity of 34.3% and specificity of34.82 at a cut-off value of 34.82.the sensitivity was 34.3% and the specificity was90.5%,with a Yordon index of 0.248.Part Ⅱ: Comparison of the PHE volumes calculated by the Tada formula and 3D Slicer software and the mean of the sum of the two calculations revealed statistically significant differences in PHE volumes and relative PHE volumes within 24 h of onset and on day 7 of onset in both ApoEε3 and ApoEε4 groups.Comparison of the remaining imaging features and associated complications revealed statistically significant differences in brain herniation,HIHSS at admission,and GCS at admission between the ApoEε3 and ApoEε4 groups.The groups were divided into good prognosis and poor prognosis according to the m RS score,with statistically significant differences between the two groups for pulmonary infection,gastrointestinal bleeding,PHE volume within 24 h of onset,PHE volume on day 7 of onset,relative PHE volume on day 7 of onset,hemorrhage breaking into the ventricles,brain herniation,and carrying the ApoEε4 gene.Binary logistic regression of single factors affecting prognosis showed that lung infection,ApoEε4,and PHE volume at day 7 of onset were independent risk factors for poor prognosis in patients with ICH(P < 0.05).ROC curves were plotted to assess the predictive value of ApoEε4,day 7onset PHE volume,and pulmonary infection on the prognosis of ICH,with a day 7onset PHE volume AUC of 0.703(95% CI: 0.602-0.804,P <0.001),corresponding to a sensitivity of 72.1% and specificity of 72.1% when the day 7 onset PHE volume cut-off value was 4.34.The sensitivity,specificity,positive and negative predictive values for ApoEε4 to predict poor prognosis in patients were 0.364,0.56,0.701 and0.6,respectively,with a Jorden index of 0.347,corresponding to an AUC of 0.673(P=0.002).The sensitivity,specificity,positive and negative predictive values for lung infection to predict poor prognosis were 0.756,0.422,0.466 and 0.722,respectively,with a Jordon index of 0.179,corresponding to an AUC of 0.648(P=0.009).Part Ⅲ: Pearson correlation analysis showed that PHE volume within 24 h of onset was positively correlated with haematoma volume within 24 h of onset and with absolute neutrophil count on admission and neutrophils on admission(P < 0.05),and PHE volume on day 7 of onset was positively correlated with haematoma volume within 24 h of onset and with haematoma volume on day 7 of onset(P < 0.05).The differences in Cyp A,NF-κB and MMP-9 in cerebrospinal fluid on days 1,3 and 5between the two groups of patients were not statistically significantly different by ELISA for ApoEε3 and ApoEε4.Conclusions:Part Ⅰ: After ICH,patients carrying the ApoEε4 gene had significantly higher white blood cell counts and absolute neutrophil values on admission compared to patients carrying the ApoEε3 gene.Initial haematoma volume,ApoEε4,white blood cell counts and absolute neutrophil values in ICH can be used as independent risk factors for poor short-term prognosis in patients with ICH.Part Ⅱ: After ICH,patients carrying the ApoEε4 gene had more peri-haematoma oedema within 24 h of onset and on day 7 than patients carrying the ApoEε3 gene.ApoEε4,lung infection and peri-haematoma oedema volume on day 7 of onset could be independent risk factors for poor short-term prognosis in patients with cerebral haemorrhage.Part Ⅲ: After ICH,there was a positive correlation between peri-haematoma oedema volume within 24 h of onset and absolute white blood cell count and neutrophil values on admission;there was no correlation between peri-haematoma oedema volume on day 7 of onset and absolute white blood cell count and neutrophil values on admission.