Multiparametric Clinical Study Of Multiethnic Patients With Aneurysmal Subarachnoid Hemorrhage In The Karst

Objective:Aneurysmal subarachnoid hemorrhage(aSAH)is a subtype of stroke with high morbidity and mortality.Guizhou is a typical karst region,and the main ethnic minority groups in this region are Miao,Bouyei,and Dong.To date,there have been no articles on aSAH patients of Miao,Bouyei,or Dong ethnic minority groups,despite the combined population of these three ethnic groups is over 20 million.The first part of this study aimed to conduct a multiparametric clinical study of these three ethnic groups.For patients with aSAH,they may experience some neurological or non-neurological complications after aSAH,which greatly affects their neurological prognosis.Due to the inherent health issues associated with obesity,overweight and obese patients with aSAH may have unique characteristics,especially in the occurrence of stroke complications.Recent studies have found that neuroinflammation and thrombotic inflammation are promising targets for early neuroprotective therapy after aSAH to prevent secondary brain injury.The second part of the study aimed to identify predictive factors for complications in overweight and obese aSAH patients,with a particular focus on the potential roles of inflammation and coagulation markers.About one-third of aSAH patients have multiple intracranial aneurysms(MIAs).The selection of surgical approaches and treatment stages are two challenging treatment strategies for multiple intracranial aneurysmal subarachnoid hemorrhage(MIA-SAH).Although the economy of Guizhou is relatively backward,our center has rich experience in the treatment of MIAs.In 2001,we proposed a zone classification standard for MIAs patients,which has not yet been widely applied abroad.The third part of the study aimed to summarize treatment experience based on a sample of over200 MIA-SAH patients in our region,and further investigate the application of zone classification in MIA-SAH treatment strategies.Finally,considering the current lack of clinical studies on aSAH with a sample size of over 300 people in Guizhou Province,the risk factors for poor prognosis of aSAH patients undergoing surgery in this region are still uncertain.The fourth part of the study aimed to investigate the poor prognosis of aSAH patients in the karst through a large sample of over 1000 patients,comparing the demographic,clinical,imaging,intervention strategies,laboratory tests,and complications of patients with poor and good prognosis,in order to analyze and identify potential risk factors.In addition,the fourth part of the study aims to record the detailed locations and treatment plans of all aneurysms,in order to provide a large sample of local aSAH patients.Methods:In the first part,we retrospectively collected the data of all Miao,Bouyei,and Dong aSAH patients undergoing surgery in our hospital over the last eight years.Comparisons were made between the Miao,Bouyei,and Dong ethnic groups,and the Bonferroni method was used to adjust the p-values of these three groups of comparisons.We evaluated the correlation between laboratory test results and clinical or SAH conditions for all three ethnic groups using Pearson correlation coefficients.Multiple logistic regression analysis was used to identify independent risk factors for disability and death among these three ethnic groups.We evaluated the discriminative ability of continuous variables of interest by drawing receiver operating characteristic(ROC)curves,selected the point with the highest Youden index as the optimal cutoff value,and calculated the area under the curve(AUC)accordingly.In the second part,a retrospective analysis was conducted on the data of overweight and obese aSAH patients who underwent aneurysm surgery at our center over the past 9 years.The body mass index(BMI)of 25.0-29.9 was defined as overweight,and BMI ≥ 30.0 was defined as obesity.Multivariate logistic regression analysis was used to determine the independent factors related to complications(delayed cerebral ischemia [DCI],rebleeding,hydrocephalus,intracranial infection,pulmonary infection,urinary tract infection,gastrointestinal hemorrhage,and deep vein thrombosis).The Pearson correlation coefficient was used to evaluate the correlation between BMI,Neutrophil/lymphocyte ratio(NLR),platelet/white blood cell ratio(PWR),and Glasgow Outcome Scale(GOS)in overweight and obese aSAH patients.We evaluated the predictive value of NLR and PWR for complications in overweight and obese aSAH patients undergoing surgery by drawing ROC curves.In the third part,we retrospectively analyzed data from patients with MIA-SAH who underwent surgery in our hospital between January 1,2014 and September 1,2022.General and aneurysmal-related characteristics of patients with different zone classifications were collected and compared between two surgical approaches.Multivariate logistic regression analysis was used to identify factors independently associated with multistage treatment options.In the fourth part,we retrospectively analyzed patients with aneurysmal subarachnoid hemorrhage who underwent surgery in our hospital between June 1,2014,and September 1,2022.The Glasgow Outcome Scale was used to evaluate outcomes at discharge,with scores of 1–3 and 4–5 considered poor and good,respectively.Demographic and clinical characteristics,imaging features,intervention strategies,laboratory tests,and complications were compared between patients with good and poor outcomes.Multivariate analysis was used to determine independent risk factors for poor outcomes.The poor outcome rate of each ethnic group was compared.We also tabulated the treatment plans of patients with different numbers of aneurysms and detailed locations of all aneurysms to provide treatment examples for this region.Results:In the first part,a total of 217 patients were included.Compared with Bouyei,Miao patients had a lower proportion of blood type O,higher triglyceride level,lower high-density lipoprotein cholesterol(HDL-C)level,higher low-density lipoprotein cholesterol(LDL-C)level,and higher apolipoproteins B level.Compared with Dong,Miao patients had a smaller aneurysm size and higher triglyceride level.Compared with Dong,Bouyei patients had a lower cerebral infarction history rate,lower hemoglobin concentration,and higher HDL-C level.Multivariate logistic regression analysis showed that Hunt-Hess grade(OR=2.207,95% CI: 1.379–3.533),modified Fisher grade(OR=2.459,95% CI: 1.452–4.165),microsurgical clipping(OR=3.190,95% CI: 1.213–8.393),aneurysm size(OR=1.160,95% CI: 1.022–1.316),and uric acid(OR=1.003,95% CI: 1.000–1.006)were independent risk factors of disability.Blood lipid indicators could distinguish these three ethnic groups very well:triglyceride distinguished Miao patients from Bouyei with 0.79 sensitivity and 0.68specificity(AUC=0.744,95% CI: 0.666–0.823,optimal cutoff value 1.26),distinguished Miao patients from Dong with 0.69 sensitivity and 0.67 specificity(AUC=0.645,95% CI: 0.546–0.744,optimal cutoff value 1.43);HDL-C distinguished Bouyei patients from Dong with 0.71 sensitivity and 0.55 specificity(AUC=0.645,95% CI: 0.546–0.744,optimal cutoff value 1.19);apolipoproteins B distinguished Miao patients from Bouyei with 0.82 sensitivity and 0.48 specificity(AUC=0.663,95% CI: 0.580–0.746,optimal cutoff value 0.86).In the second part,a total of 721 patients(553 overweight and 168 obesity)were included.The results of multivariate logistic regression analysis showed that systolic pressure(OR=1.012,95% CI 1.005–1.018;p<0.001),GCS score of 3–12(OR=1.611, 95% CI 1.072–2.419;p=0.022),modified Fisher grade 3–4(OR=2.033,95% CI1.393–2.967;p<0.001),microsurgical clipping(OR=1.765,95% CI 1.072–2.907;p=0.025),and APTT(OR=0.958,95% CI 0.924–0.993;p=0.019)were independent factors associated with DCI.GCS score 3–12(OR=1.879,95% CI 1.087–3.250;p=0.024),microsurgical clipping(OR=3.047,95% CI 1.594–5.826;p<0.001),and irregular aneurysm shape(OR=1.904,95% CI 1.096–3.310;p=0.022)were independent factors associated with rebleeding.Drinking index ≥ 40(OR=1.902,95%CI 1.108–3.267;p=0.020)and NLR(OR=1.024,95% CI 1.002–1.047;p=0.030)were independent factors associated with hydrocephalus.PWR(OR=0.946,95% CI0.896–0.998;p=0.042)was an independent factor associated with intracranial infection.Age(OR=1.028,95% CI 1.012–1.044;p<0.001),smoking index ≥ 200(OR=1.602,95% CI 1.062–2.417;p=0.025),systolic pressure(OR=1.007,95% CI1.001–1.014;p=0.032),modified Fisher grade 3–4(OR=2.798,95% CI 1.969–3.977;p<0.001),microsurgical clipping(OR=2.825,95% CI 1.652–4.832;p<0.001),PWR(OR=0.978,95% CI 0.957–0.999;p=0.040),and APTT(OR=0.943,95% CI0.909–0.979;p=0.002)were independent factors associated with pulmonary infection.NLR(OR=1.038,95% CI 1.008–1.070;p=0.012)and albumin(OR=0.889,95% CI0.831–0.951;p<0.001)were independent factors associated with urinary tract infection.Smoking index ≥ 200(OR=2.152,95% CI 1.066–4.344;p=0.032)and PWR(OR=0.948,95% CI 0.904–0.994;p=0.028)were independent factors associated with gastrointestinal bleeding.BMI(OR=1.138,95% CI 1.034–1.253;p=0.008)and NLR(OR=1.036,95% CI 1.003–1.071;p=0.033)were independent factors associated with deep venous thrombosis.BMI(r=-0.224,p<0.001)and NLR(r=-0.165,p<0.001)were negatively correlated to GOS scores,while PWR(r=0.204,p<0.001)was positively correlated to GOS scores.In the third part,a total of 226 MIA-SAH patients with 523 aneurysms were included.Among them,227 aneurysms were found in 103 patients with zone classification I,266 in 116 patients with zone classification Ⅱ,26 in 6 patients with zone classification Ⅲ,and 4 in 1 patient with zone classification Ⅳ.The proportion of patients undergoing endovascular treatment increased with higher zone classification(Ⅰ: 85.4%;Ⅱ: 94.0%;Ⅲ: 100.0%;Ⅳ: 100.0%).The proportion of patients receiving one-stage treatment decreased with higher zone classification(Ⅰ:60.2%;Ⅱ: 33.6%;Ⅲ: 0.0%;Ⅳ: 0.0%).Compared with patients undergoing microsurgical clipping,more patients undergoing endovascular treatment had zone classification Ⅱ–Ⅳ(56.9% vs.31.8%,p=0.025).Zone classification Ⅱ–Ⅳ(OR=3.821,95% CI: 2.041–7.154,p<0.001),endovascular treatment(OR=8.756,95% CI: 2.589–29.609,p<0.001),and size of all unruptured aneurysms <3 mm(OR=4.531,95% CI: 2.315–8.871,p<0.001)were each independently associated with multistage treatment.In the fourth part,a total of 1169 patients were included.348(29.8%)were ethnic minorities,and 134(11.5%)underwent microsurgical clipping.406(34.7%)patients had poor outcomes.Multivariate analysis identified age(OR [95% CI])(1.026[1.013–1.040];p<0.001),ethnic minority(0.413 [0.288–0.595];p<0.001),loss of consciousness at onset(1.839 [1.311–2.580];p<0.001),systolic blood pressure on admission(1.008 [1.002–1.014];p=0.012),Hunt–Hess grade 4–5 on admission(4.594[2.782–7.587];p<0.001),epileptic seizures(2.733 [1.602–4.663];p<0.001),modified Fisher grade 3–4(4.202 [3.051–5.786];p<0.001),microsurgical clipping(2.554[1.638–3.984];p<0.001),size of the ruptured aneurysm(1.097 [1.044–1.153];p<0.001),and CSF replacement(0.621 [0.446–0.864];p=0.005)as independent risk factors for poor outcome in the karst.Among ethnic minority minorities with a proportion of over 1%,the Dong ethnic group had the highest rate of poor prognosis,while the Shui ethnic group had the lowest rate.The top three types of aneurysms were anterior,posterior communicating,and middle cerebral artery aneurysms.Conclusions:The first part of the study is the first clinical study conducted on aSAH patients of Miao,Bouyei,and Dong ethnic minority groups.There existed unique differences in many aspects in patients from Miao,Bouyei,and Dong ethnic minority groups. Blood lipid indicators distinguished statistically these three ethnic groups very well;aneurysm size distinguished statistically Dong patients from Miao;hemoglobin distinguished statistically Dong patients from Bouyei.Hunt-Hess grade,modified Fisher grade,microsurgical clipping,aneurysm size,and uric acid were independent risk factors of disability of aSAH patients of Miao,Bouyei,and Dong ethnic minority groups in the karst.In the second part,we comprehensively summarized the eight major complications after aSAH and investigated the predictive value of hematological parameters on the occurrence of complications in overweight and obese aSAH patients in the karst.Patients with DCI,rebleeding,hydrocephalus,intracranial infection,pulmonary infection,urinary tract infection,gastrointestinal bleeding,and deep vein thrombosis had their own unique independent related factors.The NLR and PWR were promising predictors of complications in patients with overweight and obesity with aneurysmal subarachnoid hemorrhage,supporting the theory that neuroinflammation and thrombo-inflammation play important roles after aneurysmal subarachnoid hemorrhage.In the third part,we determined the clinical application value of zone classification in the treatment strategy of multiethnic MIA-SAH patients in karst,especially in the selection of surgical approach and treatment stage.The proportion of patients undergoing endovascular treatment increased with higher zone classification,while the proportion of patients receiving one-stage treatment for all aneurysms decreased with higher zone classification.Zone classification Ⅱ–Ⅳ,endovascular treatment,and sizes of all unruptured aneurysms <3 mm were independently associated with multistage treatment.Based on these findings,we recommend using zone classification in MIA-SAH treatment strategies.The fourth part of the study is the first clinical study of aSAH with a sample size of >300 in Guizhou Province,China.Outcomes at discharge varied according to ethnic group.Han patients had worse outcomes.Age,loss of consciousness at onset,systolic blood pressure on admission,Hunt-Hess grade 4–5 on admission,epileptic seizures,modified Fisher grade 3–4,microsurgical clipping,size of the ruptured aneurysm,and cerebrospinal fluid replacement were independent associated factors for aneurysmal subarachnoid hemorrhage outcomes.Considering the multi-ethnicity of the region,we performed the first comparison of patients with aSAH of different ethnic groups.These data may impact public health and guide future resource allocation and service development in Guizhou Province.