【作者】 李辉；

【导师】 曹靖；

【作者基本信息】 郑州大学 ， 人体解剖与组织胚胎学， 2022， 硕士

【摘要】 背景和目的同型半胱氨酸(homocysteine,Hcy)水平是心脑血管疾病的危险因素。有研究表明Hcy通过炎症反应、增加血管内膜厚度、促进动脉硬化可以导致心脑血管疾病的发生,因此,作为一种新的危险因素,高同型半胱氨酸血症(hyperhomocysteinemia,HHcy)在心脑血管领域日益受到人们的广泛关注,血清Hcy水平的有效控制也许可以成为预防和治疗冠心病、脑卒中的一个新的环节。但现在它与缺血性脑卒中的相关危险因素及TOAST分型的相关性研究还不是很多,基于此,我们收集临床病例探讨它们之间的关系,为临床研究提供参考数据。方法选取2021年7月1日至2021年12月31日因眩晕、复视、肢体力弱、麻木、言语不利或口角歪斜等神经功能缺损症状就诊于解放军总医院第一医学中心神经内科医学部五病区并被诊断为急性缺血性脑卒中(acute ischemic stroke,AIS)的患者进行临床回顾性研究。记录所有患者入院后的临床资料:年龄、性别、身高、体重、高血压病史、糖尿病史、高脂血症病史、房颤病史、吸烟史。并收集患者入院时的高密度脂蛋白胆固醇(High density lipoprotein cholesterol,HDL-C)、低密度脂蛋白胆固醇(Low density lipoprotein cholesterol,LDL-C)、总胆固醇(Total cholesterol,TC)、甘油三酯(Triglyceride,TG)、空腹血糖(Blood sugar,FBG)和血压(bloodpresssure,BP)等指标。采用酶联免疫分析法检测血清Hcy表达水平。所有患者采用改良Rankin量表(mRS)评分评估不同时点患者预后情况,并采用美国国立卫生研究院卒中量表评分(National Institutes of Health Stroke Scale Score,NIHSS)评估患者临床神经功能缺损情况。所有患者给予抗血小板聚集,稳定血压、血糖、调脂稳斑及改善循环等治疗。同时根据检测的Hcy水平分为Hcy<15 μmol/L组和Hcy≥15 μmol/L组,统计分析不同Hcy水平组入院时基线资料情况;不同Hcy水平与缺血性脑卒中TOAST分型的关系;不同Hcy水平与空腹血糖(FBG)、高密度脂蛋白(HDL)、低密度脂蛋白胆固醇(LDL-C)、总胆固醇(TC)、甘油三酯(TG)、血压(BP)以及白细胞介素-6(IL-6)的相关性;AIS患者不同神经功能缺损程度血清Hcy水平的比较;不同Hcy水平与颈动脉内膜厚度的相关性;AIS患者住院期间Hcy水平与预后量表评分的相关性;并统计影响AIS患者住院期间预后的因素,进行单因素分析和多因素logistic回归分析;以及Hcy水平对急性脑卒中患者不良预后预测的ROC曲线分析。不同组之间的分类变量采用交叉列表和X2分析,并通过独立t检验和单因素方差分析进行分析。结果共纳入符合要求的患者114例,全面收集患者的临床资料。根据同型半胱氨酸水平分为两组。(1)两组患者基线资料比较:两组患者在年龄、吸烟史、收缩压、舒张压、高血压病史、冠心病病史、高脂血症病史、房颤病史方面相比差异无统计学意义(P>0.05);在性别、病程、入院时NIHSS、冠心病病史方面相比差异具有统计学意义(P<0.05)。(2)两组患者TOAST分型例数差异均无统计学意义(P>0.05)。(3)影响AIS患者Hcy水平的单因素分析:两组患者FBP、CRP、TG、LDL-C、IL-6相比差异具有统计学意义(P<0.05);而TC、HDL-C相比差异无统计学意义(P>0.05)。(4)影响AIS患者Hcy水平的多因素分析:FBP、LDL-C、IL-6的回归系数分别为0.523,1.123,0.295并且呈现出0.01水平的显著性(P<0.01),意味着上述因素会对Hcy水平产生显著的正向影响关系。CRP的回归系数值为0.150,并没有呈现出显著性(P=0.098>0.05),并不会对Hcy水平产生影响关系。(5)两组颈动脉内膜厚度的对比:Hcy≥15 μ mol/L水平组的IMT厚度(3.068±0.508mm)明显厚于Hcy<15 μ mol/L水平组IMT厚度(1.337±0.620),差异具有统计学意义(p<0.01)。(5)两组神经受损程度相比:不同神经受损程度样本对于Hcy水平均有差异性(P<0.05),患者的血清Hcy水平随着神经缺损程度的增加而升高。根据mRS评分分为两组,mRS≤2分为良好功能结局组,mRS>2分为不良功能结局组。(1)两组间Hcy水平差异:其中不良功能结局组对于Hcy呈现出0.01水平显著性(t=-3.781,p=0.000)。提示Hcy水平是影响AIS患者预后的因素。(2)两组间TOAST分型比较:mRS分组对于TOAST分型呈现出0.05水平显著性(X2=10.835,p=0.022<0.05),通过百分比对比差异可知,mRS>2分组选择CE的比例21.43%,明显高于mRS≤2分组的选择比例15.91%。mRS>2分组选择LAA的比例55.71%,明显高于mRS≤2分组的选择比例31.82%。mRS≤2分组选择SAO的比例36.36%,明显高于mRS>2分组的选择比例15.71%。提示LAA、CE型脑卒中,不良功能结局比例更高。(3)影响AIS患者住院期间预后的单因素分析:两组间 Hcy、FBP、CRP、LDL-C、IL-6、TG、入院时 NIHSS、第 7 天 NIHSS比较有显著差异(P<0.05),提示上述因素会影响AIS患者预后,两组间年龄、TC、HDL-C、收缩压、舒张压比较无明显差异(P>0.05)。(4)影响AIS患者住院期间预后的多因素Logistic回归分析:血清Hcy水平、年龄、空腹血糖、TC、TG、HDL-C、IL-6、IMT、第7天NIHSS并不会对卒中患者不良功能结局产生影响关系。入院时NIHSS、CRP会对卒中患者不良功能结局产生显著的正向影响关系。用受试者工作特征(ROC)曲线分析Hcy水平指标预测卒中不良功能结局曲线下面积(AUC):Hcy对应的AUC值为0.701,意味着Hcy对于mRS不良功能结局的预测价值比较高,并且对应最佳界值为0.421(此时敏感度为0.671,特异度为0.750)。总结可知:Hcy对卒中不良功能结局有着较高的预测价值。结论血清Hcy水平与空腹血糖(FBP)、低密度脂蛋白胆固醇(LDL-C)、白介素-6(IL-6)的高低及颈动脉内膜厚度有着密切相关性。AIS患者血清Hcy水平与TOAST分型无关。AIS患者血清Hcy水平随着神经受损程度的增加而升高。AIS患者血清Hcy对预后有较高的预测价值。更多还原

【Abstract】 Background and ObjectiveHomocysteine(Hcy)level is a risk factor for cardiovascular and cerebrovascular diseases.Studies have shown that Hcy can lead to the occurrence of cardiovascular and cerebrovascular diseases through inflammatory reaction,increasing the thickness of vascular intima,and promoting arteriosclerosis,Therefore,as a new risk factor,hyperhomocysteinemia(HHcy)has attracted more and more attention in the field of cardiovascular and cerebrovascular diseases.Effective control of serum Hcy level can become a new link in the prevention and treatment of coronary heart disease and stroke.However,there are not many studies on the correlation between serum Hcy level and risk factors of ischemic stroke and TOAST classification.Based on this,we collected clinical cases to explore the relationship between them and provide reference data for clinical research.MethodsFrom July 1,2021 to December 31,2021,we selected patients who were diagnosed as acute ischemic stroke(AIS)in the fifth ward of the Department of Neurology Medicine of the First Medical Center of the PLA General Hospital due to vertigo,diplopia,weak limbs,numbness,poor speech or angular deviation and other neurological defects.The clinical data of the two groups after admission were recorded:age,sex,height,weight,hypertension history,diabetes history,hyperlipidemia history,atrial fibrillation history,smoking history.High density lipoprotein(HDL),low density lipoprotein cholesterol(LDL-C),total cholesterol(TC),triglyceride(TG),fasting blood glucose(FBG)and blood pressure(BP)were collected at admission.Serum Hcy expression was detected by ELISA.All patients used the modified Rankin Rating Scale(mRS)to evaluate the prognosis of patients at different time points,and the National Institutes of Health Stroke Scale Score(NIHSS)to evaluate the clinical neurological deficit of patients.All patients were treated with anti platelet aggregation,stabilizing blood pressure,blood glucose,regulating lipid and plaque,and improving circulation.At the same time,Hcy<15 according to the detected Hcy level μ Mol/L group and Hcy≥15μ In the mol/L group,the baseline data of different Hcy levels at admission were statistically analyzed;The relationship between different Hcy levels and TOAST classification of ischemic stroke;The correlation between different Hcy levels and fasting blood glucose(FBG),high-density lipoprotein(HDL),low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),triglycerides(TG),blood pressure(BP)and interleukin-6(IL-6);Comparison of serum Hcy levels in AIS patients with different neurological deficits;The correlation between different Hcy levels and carotid intima thickness;The correlation between Hcy level and prognosis scale score of AIS patients during hospitalization;The factors influencing the prognosis of AIS patients during hospitalization were analyzed by single factor analysis and multivariate logistic regression analysis;And the ROC curve analysis of Hcy level in predicting the adverse prognosis of patients with acute stroke.The categorical variables between different groups were analyzed by cross listing and X2 analysis,and independent t-test and one-way ANOVA.ResultsA total of 114 eligible patients were included,and their clinical data were comprehensively collected.They were divided into two groups according to the level of homocysteine.(1)Comparison of baseline data between the two groups:there was no significant difference between the two groups in terms of age,smoking history,systolic blood pressure,diastolic blood pressure,hypertension history,coronary heart disease history,hyperlipidemia history,and atrial fibrillation history(P>0.05);There were statistically significant differences in gender,course of disease,NIHSS at admission,and history of coronary heart disease(P<0.05).(2)There was no significant difference in the number of TOAST typing cases between the two groups(P>0.05).(3)Single factor analysis on the level of hcy in AIS patients:There were significant differences in FBP,CRP,TG,LDL-C and IL-6 between the two groups(P<0.05);There was no significant difference between TC and HDL-C(P>0.05).(4)Multivariate analysis of factors influencing the level of hcy in AIS patients:the regression coefficients of FBP,LDL-C and IL-6 were 0.523,1.123 and 0.295,respectively,and showed a significant level of 0.01(P<0.01),indicating that the above factors would have a significant positive impact on the level of hcy.The regression coefficient value of CRP was 0.150,which did not show a significant difference(p=0.098>0.05),and did not affect the level of hcy.(5)Comparison of carotid intima thickness between two groups:hcy≥15 μ IMT thickness(3.068±0.508mm)in the mol/L level group was significantly thicker than that in hcy<15 μThe IMT thickness in the mol/L level group was(1.337±0.620),and the difference was statistically significant(p<0.01).(5)Compared with the degree of nerve damage in the two groups,the levels of hcy in samples with different degrees of nerve damage were different(P<0.05),and the level of serum Hcy in patients increased with the increase of the degree of nerve damage.According to the mRS score,the patients were divided into two groups.The patients with mRS ≤2 were classified as good functional outcome group,and those with mRS>2 were classified as bad functional outcome group.(1)Hcy level difference between the two groups:the dysfunctional group showed a significant 0.01 level for hcy(t=-3.781,P=0.000).It is suggested that hcy level is a prognostic factor in AIS patients.(2)Comparison of TOAST classification between the two groups:mRS group showed 0.05 level significance for TOAST classification(X2=10.835,P=0.022<0.05).It can be seen from the percentage difference that 21.43%of the group with mRS>2 chose CE,which was significantly higher than 15.91%of the group with mRS≤2.55.71%of the group with mRS>2 chose LAA,which was significantly higher than 31.82%of the group with mRS≤2.The proportion of SAO in groups with mRS≤2 was 36.36%,which was significantly higher than that in groups with mRS>2(15.71%).It suggests that LAA and CE stroke have a higher proportion of adverse functional outcome.(3)Univariate analysis on the prognosis of AIS patients during hospitalization:there were significant differences between the two groups in hcy,FBP,CRP,LDL-C,IL-6,TG,NIHSS at admission,and NIHSS on the 7th day(P<0.05),suggesting that the above factors would affect the prognosis of AIS patients,and there was no significant difference between the two groups in age,TC,HDL-C,systolic blood pressure,and diastolic blood pressure(P>0.05).(4)Logistic regression analysis of multiple factors influencing the prognosis of AIS patients during hospitalization:serum Hcy level,age,fasting blood glucose,TC,TG,HDL-C,IL-6,IMT,and NIHSS on the 7th day did not affect the adverse functional outcome of stroke patients.NIHSS and CRP at admission will have a significant positive impact on the adverse function outcome of stroke patients.The area under the stroke adverse function outcome curve(AUC)predicted by the HCY level index using the ROC curve:the AUC value corresponding to Hcy is 0.701,which means that Hcy has a relatively high predictive value for the adverse function outcome of mRS,and the corresponding optimal threshold is 0.421(at this time,the sensitivity is 0.671,and the specificity is 0.750).It can be concluded that hcy has a high predictive value for the adverse functional outcome of stroke.ConclusionSerum Hcy level is closely related to fasting blood glucose(FBP),low density lipoprotein cholesterol(LDL-C),interleukin-6(IL-6)and carotid intima thickness.Serum Hcy level in AIS patients was not related to TOAST classification.The serum Hcy level of AIS patients increased with the increase of the degree of nerve damage.Serum Hcy in AIS patients has a high predictive value for prognosis.更多还原