MTHFR基因多态性检测对判断卒中患者再发预后的临床意义

目的 前瞻性观察N5、N10-亚甲基四氢叶酸还原酶(MTHFR)基因C677T多态性对缺血性卒中(IS)再发及死亡事件发生的影响,为进一步对IS综合干预提供有用情报.方法 检测245例IS患者及52例健康对照者空腹血浆同型半胱氨酸(Hcy)水平及MTHFR基因C677T多态性,并在5年内追踪观察患者IS再发及死亡事件的发生情况.结果 T/T纯合型IS再发率显著高于C/T杂合型和C/C野生型(P<0.05),C/T杂合型高于C/C野生型,但差异无显著性(P>0.05).各基因型之间随访脑梗死再发率、TIA再发率、多次再发患者比例、及死亡发生率差异均无显著性,但均为T/T纯合型高于C/T杂合型,后者高于C/C野生型.Logistic回归分析显示Hcy升高是再发IS的独立危险因素(OR为1.171,95%CI:1.118～1.227,P<0.01),而MTHFR基因C677T突变未进入回归模型.结论 血浆Hey水平升高与IS再发密切相关,MTHFR基因C677T突变导致血浆Hey水平升高,是再发IS遗传易感因素.

Abstract：

Objective To prospectively observe the possible effect of the gene C677T polymorphism of methylene tetrahydrofolate reduetase(MTHFR)on the recurrence of isehemie stroke(IS)and death events in hope for providing a new theoretical evidence for the therapy and the prophylaxis of IS.Methods We determined the free plasma homocysteine (Hey)and MTHFR gene C677T polymorphism of 245 patients with IS and 52 age and gender-matched healthy controls,then we observed the recurrence of IS and death events within a 5-years follow-period.Results The rate of recurrent IS of T/T genotype group was significantly higher than C/T and C/C genotype group(P<0.05),and that of C/T genotype group was higher than C/C genotype group,but the deference Was not statistically significant.The deference of the rate of recurrent cerebral infarction,TIA,the proportion of patients who suffered multiple recurrence,and the death rate among the 3 genotype groups Was not statistically significant(P>0.05),but the occurred rate of every kind of event in T/T genotype group was higher than C/T genotype group,and that of the latter Was higher than C/C genotype group.By forward stepwise logistic analysis,we found that Hey Was an independent risk factor of recurrent IS(OR=1.171;95%CI:1.118～1.227;P<0.01),but gene C677T mutation of MTHFR Was not in the regression model.Conclusions Hey is closely correlated with prognosis of recurrent IS.Gene C677T mutation of MTHFR can cause the rising of Hey and was susceptibility gene of recurrent IS.     

Hhcy对缺血性脑卒中患者再发缺血性血管事件及相关死亡事件的影响

目的探讨高同型半胱氨酸血症(hyperhom ocysteinemia,Hhcy)对缺血性卒中(IS)患者再发、死亡及冠状动脉和外周动脉缺血性事件发生的影响,为进一步对缺血性血管病的综合干预提供依据。方法检测245例IS患者空腹血浆同型半胱氨酸(Hcy)水平,并参照同期选取的52例健康体检者为对照者按血浆Hcy水平将其分为Hhcy组和非Hhcy组,追踪观察两组患者IS再发、死亡及冠状动脉和外周动脉缺血事件的发生情况。结果其中Hhcy组IS再发率(52.63%)显著高于非Hhcy组(24.67%)(P<0.01);死亡事件发生率(12.63%)亦显著高于非Hhcy组(3.33%)(P<0.01);冠脉缺血事件发生率(18.95%)明显高于非Hhcy组(10.00%)(P<0.05);外周动脉缺血事件发生率两组分别为5.26%和2.67%,差异无统计学意义(P>0.05);并发2种以上缺血性事件的患者Hhcy组(17.89%)显著多于非Hhcy组(5.33%)(P<0.01);Hhcy组患者5年内缺血性血管事件发生率(57.89%)显著高于非Hhcy组(32.00%)(P<0.01);Logistic回归分析发现,Hcy升高是IS患者缺血性血管事件再发的独立危险因素(OR分别为1.174;95%CI1.119~1.233;P<0.05)。结论 Hhcy与IS患者缺血性血管事件再发及死亡预后密切相关。     

高血浆同型半胱氨酸对急性缺血性脑卒中预后的影响

目的观察高血浆同型半胱氨酸(HHCY)与急性缺血性脑卒中预后的关系。方法收集本院2007年1月~2009年10月急性缺血性脑卒中住院患者,选出血浆同型半胱氨酸(HCY)正常患者及高血浆同型半胱氨酸患者各50例,对两组治疗14d后的效果进行比较。结果高血浆同型半胱氨酸组患者恢复情况明显较血浆同型半胱氨酸正常组差。结论高同型半胱氨酸血症是导致急性缺血性脑卒中预后不佳的一种重要因素。     

高同型半胱氨酸血症与TIA患者责任血管病变程度的关系

目的 探讨高同型半胱氨酸血症(Hhcy)与颈内动脉系统短暂性脑缺血发作(TIA)患者责任血管病变程度的关系,进而为动脉硬化及TIA患者的治疗提供新的理论依据.方法 测定119例颈内动脉系统TIA患者和52例健康对照者空腹血浆同型半胱氨酸(Hcy),以经颅多普勒超声(TCD)检查对患者责任血管状况进行评价,并以对照组Hcy检测结果将患者分为Hhcy组和非Hhcy组进行研究.结果 Hhcy组患者责任血管病变较非Hhcy组明显,差异具有统计学意义(P=0.002),经Ordinal回归分析,显示Hhcy是TIA患者责任血管病变的独立危险因素(P<0.01),优势比为4.707(95%CI:1.992-11.123).结论 Hhcy与TIA患者责任血管病变密切相关.

Abstract：

Objective To explore the possible relationship of hyperhomocysteinemia and the lesion degree of relative arteries in patients with transient ischemic attacks (TIA) of internal carotid artery system in hope for finding a new theoretical evidence for the therapy of artery atherosclerosis and TIA. Methods We determined the free plasma homocysteine (Hcy) of 119 patients with internal carotid artery system TIA and 52 age-and gender-matched healthy controls by high-per-formance liquid chromatography, and assessed the relative arteries of patients by transcranial Doppler sonography. And we divided the patients into hyperhomocysteinemia (Hhcy) group and non-hyperhomocysteinemia (Nhhcy) group according to the outcomes, then we researched the lesion degree of relative arteries of the groups. Results There was statistical deference in the lesion degree of relative arteries between Hhcy and Nhhcy group. By Ordinal regression analysis,we found that Hhcy was an independent risk factor for the artery lesion of TIA patients ( P < 0.01 ;OR = 4. 707 ;95 % CI : 1. 992-11. 123 ).Conclusion Hhcy might be closely correlated with the relative artery lesion in TIA patients.     

同型半胱氨酸水平对急性脑梗死再发的影响

目的探讨同型半胱氨酸水平对急性脑梗死患者再发的影响。方法选择我院2009-09—2011-09收治的急性脑梗死患者160例,随机分为观察组和对照组。2组均给予急性脑梗死常规治疗,观察组同时口服叶酸片,5mg/d;维生素B6,10mg/d。治疗12个月后,清晨空腹抽取静脉血检测患者血同型半胱氨酸水平。观察治疗1a内脑梗死的再发情况。结果 2组治疗前同型半胱氨酸水平比较,差异无统计学意义(P>0.05);观察组治疗后同型半胱氨酸水平低于治疗前,差异有统计学意义(P<0.05);对照组治疗后同型半胱氨酸水平与治疗前比较,差异无统计学意义(P>0.05);2组治疗后比较差异有统计学意义(P<0.05)。观察组1a内脑梗死再发率为16.2%,对照组为20.0%,2组比较差异无统计学意义(P>0.05)。结论补充维生素B6和叶酸有助于降低急性脑梗死患者同型半胱氨酸水平,但对急性脑梗死的再发情况影响不大。     

高同型半胱氨酸血症对急性脑梗死短期预后的影响

目的探讨高同型半胱氨酸血症(HHcy)与急性脑梗死患者短期预后之间的关系。方法测定165例急性脑梗死患者空腹血浆Hcy浓度,将患者分为HHcy组和非HHcy组,并在其入院时和治疗14d后进行改良Rankin量表(MRS)评分。结果入院时非HHcy组和HHcy组患者MRS评分中生活自理(MRS评分≤2分)人数和不能自理(MRS评分≥3分)人数的百分比之间无统计学差异(P>0.05),经相同药物治疗14d后,非HHcy组患者中生活自理人数的百分比较HHcy组患者显著升高(P<0.01),不能自理人数的百分比较HHcy组患者显著降低(P<0.01),非HHcy组患者中生活不能自理得到改善人数的百分比较HHcy组患者也显著升高(P<0.01)。结论HHcy组急性脑梗死患者的短期预后比非HHcy组差,降低HHcy对于缺血性脑血管病具有重要的预防和治疗意义。     

高同型半胱氨酸血症对急性脑梗死近期预后的影响

目的:探讨高同型半胱氨酸血症(Hhcy)对急性脑梗死近期预后的影响,以期为脑梗死干预治疗奠定理论基础。方法:测定121例急性脑梗死患者和52例健康对照者空腹血浆总同型半胱氨酸,以此结果将患者分为Hhcy组和非Hhcy组,对两组患者神经功能缺损和日常生活能力进行追踪观察。结果:Hhcy和非Hhcy组患者发病3天内神经功能缺损和发病第7、14天神经功能缺损和日常生活能力评分无显著差异(P>0.05);发病第30、90、180天,Hhcy组神经功能缺损评分显著高于非Hhcy组,而日常生活能力评分显著低于非Hhcy组(P<0.05)。结论:Hhcy不利于急性脑梗死患者近期康复。     

高同型半胱氨酸血症对脑缺血再灌注损伤影响的实验研究

目的：探讨高同型半胱氨酸血症（HHcy）对脑缺血再灌注损伤的影响。方法：制备HHcy大鼠大脑中动脉缺血再灌注损伤模型，检测缺血l、2和4h再灌注24h不同时间窗各组大鼠脑梗死体积及血浆总同型半胱氨酸（tHcy）、超氧化物歧化酶（SOD）和丙二醛（MDA）水平。结果：HHcy组大鼠脑缺血再灌注不同时间窗各组分别较相应对照组脑梗死体积增加，SOD水平降低，MDA水平增高，差异均有统计学意义（均P〈0．05）；HHcy组和对照组大鼠脑缺血再灌注不同时间窗各组脑梗死体积的差值随缺血时间的延长而增加（均P〈0．05），但SOD与MDA水平的差值各组间无统计学意义（均P〉0.05）。结论：HHcy可能通过促进氧自由基产生等作用加重脑缺血再灌注损伤。     

急性脑血管病与血浆同型半胱氨酸水平关系研究

血浆同型胱氨酸(Hcy)又称高半胱氨酸,是一种机体内不能合成的含硫氨基酸,只能从食物中的甲硫氨酸转变而来.近年来许多研究表明,Hcy水平可能是脑血管病(CVD)发生、发展的重要独立危险因素.此研究对急性CVD患者血浆Hcy水平与CVD的发病、类型及病情轻重之间的关系进行了探讨.     

高同型半胱氨酸血症与缺血性脑卒中关系的探讨

目的探讨高同型半氨酸血症与缺血性脑卒中的关系。方法对160例缺血性脑卒中患者和100例健康者进行对照、统计分析。结果缺血性脑卒中患者同型半胱氨酸水平高于健康对照者,差异有统计学意义(P<0.05)。结论高同型半胱氨酸血症与缺血性脑卒中有密切关系,可能是导致缺血性脑卒中发生的独立危险因素。     

脑血管狭窄对急性缺血性卒中患者卒中复发的影响

目的：研究急性缺血性卒中患者脑血管狭窄与卒中再发和预后的关系。方法：急性缺血性卒中患者197例，依据经颅多普勒（TCD）和（或）MRA、DSA检查结果，分成血管狭窄组与非狭窄组。比较两组平均随访25．69个月时发生的卒中、短暂性脑缺血发作（TIA）、心肌梗死和死亡。采用logistic回归分析影响卒中再发和预后的因素，Kaplan-Meier生存曲线评价卒中的风险和累积生存率，采用对数秩和检验比较两组的生存时间。结果：在随访的197例患者中，失访8例，共有189例资料完整。狭窄组（32．6％）与非狭窄组（15％）的卒中发生率（P=0．01）和预后（P=0．014）有显著差异；狭窄组50％的卒中再发时间为47个月，显著短于非狭窄组的53个月（P=0．0145）。结论：脑血管狭窄是影响急性缺血性卒中预后的因素，有血管狭窄者卒中再发率高于无脑血管狭窄者。     

Burden of Premature Atrial Complexes and Risk of Recurrent Stroke and Death in Patients with Mild to Moderate Ischemic Stroke

BackgroundPremature atrial complexes (PACs) meet increased attention as a potential intermediary between sinus rhythm and atrial fibrillation (AF). Patients with even high numbers of PACs do not fulfill current guidelines for oral anticoagulation treatment though an associated stroke risk is suspected. Objective: We aimed to determine whether a high number of PACs or runs of AF less than 30 seconds in 2-day continuous electrocardiogram (ECG) recording was associated with risk of recurrent ischemic stroke/transient ischemic attack (TIA) or death in a large cohort of patients with acute ischemic stroke or TIA and no prior AF.MethodsWe performed 48 hours continuous ECG recording within 1 week after ischemic stroke/TIA. PACs were reported as mean number of PACs per hour. Patients were followed in Danish Stroke Registry, Danish Civil Registration System, and Danish National Patient Registry. Cox Regression analysis was used to calculate hazard ratios.ResultsWe included 1507 patients with TIA (40%) or ischemic stroke (60%), of which 98.7% had mild to moderate strokes. Mean age was 72.9 (7.8) years, 43.4% were females. Follow-up was 2.3 (1.3) years. Hazard ratio for recurrent stroke/TIA or death did not differ between quartiles of PAC burden, nor did any of the 2 components of this composite endpoint. Nonsustained AF less than 30 seconds was not associated with higher risk of recurrent stroke/TIA or death.ConclusionsIn a large cohort of patients with recent ischemic stroke or TIA, burden of PACs or nonsustained AF less than 30 seconds were not associated to higher risk of recurrent stroke/TIA or death.     

急性缺血性脑卒中患者神经源性丝氨酸蛋白酶抑制剂的表达与其预后的关系

目的探讨急性缺血性脑卒中(AIS)患者神经源性丝氨酸蛋白酶抑制剂(NSP)的表达与其预后的关系。方法选择发病72 h之内的119例AIS住院患者(AIS组)作为研究对象,用双抗体夹心酶联免疫分析法测定其入院时血清NSP含量,并以改良Rankin量表(mRS)作为脑卒中3个月后的预后评判标准,将mRS≥2分者为预后不良(45例),mRS2分为预后良好(74例)。同时选择104例老年体检者为对照组。结果 AIS组NSP水平较对照组升高(P=0.000);预后良好患者其入院时梗死灶体积和美国国立卫生研究院卒中量表评分(NIHSS)明显小于预后不良患者(P0.05);且预后良好患者入院时NSP水平高于预后不良患者(P0.05)。对预后有影响且差异有统计学意义的各项指标经Logistic回归分析,NSP水平与预后有明显关系(OR=0.497 9,95%CI:0.269 8~0.918 8,P0.05)。结论 AIS患者的NSP表达可能与其预后有关。     

Serum Copeptin Predicts Severity and Recurrent Stroke in Ischemic Stroke Patients

Several studies investigated the prognostic role of copeptin in stroke. The aim of this study is to assess copeptin levels in serum, and investigate their associations with risk of recurrent stroke in a 1-year follow-up study in patients with ischemic stroke. In this post hoc analysis, serum levels of copeptin and NIH stroke scale (NIHSS) were measured at the time of admission in a cohort of 316 patients with ischemic stroke. The end point was stroke recurrence after 1-year follow-up. We used logistic regression model to assess the relationship between copeptin levels and risk recurrent stroke. Logistic regression analysis considering traditional risk factors showed a relationship between serum copeptin levels and moderate-to-high clinical severity when serum copeptin was used as a continuous variable (OR, 1.05; 95% CI, 1.03–1.09). In the follow-up, 54 patients (17.1%) had a stroke recurrence. The stroke recurrence events distribution across the copeptin quartiles ranged between 5.1% (first quartile) to 23.1% (fourth quartile). In multivariate models comparing the third (OR = 2.78; 95% CI 1.85–3.53) and fourth quartiles (OR = 4.00; 95% CI 2.86–6.50) against the first quartile of the copeptin, levels of copeptin were associated with stroke recurrence events. A higher serum copeptin level is a predictor of both severity at admission and stroke recurrence at 1-year in stroke patients.     

Serum Neurofilament Light Predicts Severity and Prognosis in Patients with Ischemic Stroke

Serum neurofilaments are markers of axonal injury. We investigated whether serum neurofilament light (sNfL) is a potential prognostic marker of functional outcome in Chinese patients with acute ischemic stroke (AIS). From May 2015 to December 2018, consecutive patients with AIS from the Department of Neurology of the Second Hospital of Jilin University were included. sNfL concentration was tested at baseline, and stroke severity was analyzed at admission using the NIHSS score. Functional outcome was assessed at discharge by the modified Rankin scale (mRS). The sNfL concentration was tested in 343 patients with a median value of 17.8 (IQR, 13.4–25.2) pg/ml. sNfL concentration paralleled lesion size (P = 0.035). At admission, 174 patients were defined as moderate-to-high stroke (NIHSS ≥ 5); the sNfL concentration in those patients were higher than that observed in patients with minor clinical severity [21.2 (IQR, 15.1–31.7) vs. 14.9 (11.8–19.4) pg/ml, P < 0.001]. For each 1 quartile increase of sNfL concentration, the unadjusted and adjusted risk of moderate-to-high stroke increased by 202% (with the OR of 3.04 (95% CI 2.15–4.32), P < 0.001) and 102% [2.02 (1.10–3.16), P = 0.001), respectively. At discharge, 85 patients (24.8%) had poor functional outcome (mRS, 3–6); the sNfL concentration in those patients were higher than that observed in patients with good outcome [24.1 (IQR, 18.8–33.9) vs. 15.7 (11.9–21.8) pg/ml, P < 0.001]. For each 1 quartile increase of sNfL concentration, the unadjusted and adjusted risk of poor outcome increased by 236% [with the OR of 3.36 (95% CI 2.23–5.06), P < 0.001] and 102% [2.29 (1.37–3.82), P < 0.001], respectively. The results show sNfL is meaningful blood biomarker to monitor stroke severity and functional outcome in ischemic stroke, suggesting that sNfL may play a role in stroke progression.     

阻塞性睡眠呼吸暂停低通气综合征对急性脑梗死患者认知功能的影响

目的探讨阻塞性睡眠呼吸暂停低通气综合征(obstructive sleep apnea-hypopnea syndrome,OSAHS)对急性脑梗死患者认知功能的影响,为血管性认知障碍的早期防治提供依据。方法对经头颅CT或MRI证实的急性脑梗死患者(41例,男21例,女20例)均进行多导睡眠图(polysomnogram,PSG)、简易智能筛查(mini-mental state examination,MMSE)、画钟试验(clock drawing task,CDT)、词语流畅试验(verbal fluency test,VFT)、听觉事件相关电位(P300)检测。结果 41例患者完成所有检查。MMSE评分27分者27例(65.85%),CDT评分4分者19例(46.34%),VFT评分15分者16例(39.02%)。依PSG检查结果分为OSAHS组(21例),非OSAHS组(20例)。OSAHS组MMSE、CDT分值低于非OSAHS组,两组比较无统计学差异(P0.05),亚组分析显示中-重度OSAHS组MMSE、CDT得分为23.67±5.12,2.67±1.53,非OSAHS组为24.85±3.15,3.1±1.2,两组比较有统计学差异(P0.05)。P300检查显示与非OSAHS组比较OSAHS组FZ、CZ、PZ潜伏期明显延长,FZ、CZ潜伏期比较有统计学差异(P0.05),中重度OSAHS组较非OSAHS组PZ潜伏期显著延长(P0.005)。各组P300的波幅无统计学差异(P0.05)。结论 OSAHS可加重急性脑梗死者的认知功能障碍,且与其严重程度相关。P300检查较MMSE、CDT更敏感。