【作者】 杨永君；

【导师】 金星；

【作者基本信息】 山东大学 ， 普通外科， 2009， 博士

【摘要】 目的斑块脱落后栓塞颅内动脉是颈动脉粥样硬化患者产生缺血性脑中风的主要机制之一。颈动脉的粥样硬化斑块引起全部缺血性脑中风的比例是8%到29%。治疗颈动脉粥样硬化斑块狭窄性疾病的目的就是减少致残性脑中风的发生率,和降低由脑动脉栓塞引起的与脑中风相关的死亡率。现在,更多的专家认为单纯根据颈动脉的狭窄程度作为颈动脉内膜切除术的手术指征是不充分的。对无症状的严重颈动脉狭窄患者,采用颈动脉内膜切除术预防缺血性脑中风是有效的,但是性价比不高。研究显示,对无症状的严重颈动脉狭窄患者施行颈动脉内膜切除术,85例手术才能预防1例缺血性脑中风。所以,如何在严重颈动脉狭窄患者中,准确地鉴别出有斑块破裂倾向,容易引起缺血性脑中风的易损斑块,有效地和准确地预防缺血性脑中风,是一个重要课题。现代超声方法具有无创、可重复的特点,可以诊断颈动脉狭窄引起的血液动力学改变,同时可以对引起颈动脉狭窄的斑块特征进行诊断。在国外有80%接受颈动脉内膜切除术治疗的患者,颈动脉超声是手术前唯一的影象学检查方法。所以颈动脉超声在颈动脉粥样硬化性狭窄疾病的诊断和随访中起着重要的作用。本论文采用纵向观察的方法对以下内容进行了分析研究:(1)颈动脉斑块狭窄引起的血流速度增加对局部压力梯度的影响;(2)斑块回声特征对脑中风发生率的影响;(3)压力梯度和斑块回声特征对斑块稳定性的影响。方法从2004到2008,共有1408例次患者,2816例次颈动脉超声检查,对其中的174个阳性病例分别从血压压力梯度、斑块的回声特征进行了分析。对危险因素和神经系统的症状进行了定义。主要观察终点包括(1)颈动脉狭窄发展成完全阻塞,(2)新发生的中风,(3)任何原因引起的死亡。采用B型超声、彩色多普勒和波谱分析方法,从前、侧和侧后三个切面对颈动脉分叉和颈内动脉进行检查。彩色多普勒和波谱分析方法用于测量颈动脉测量狭窄程度。对颈内动脉完全阻塞的超声诊断为彩色多普勒测不到有血流存在,波谱分析显示没有血流搏动,并且颈总动脉远端的舒张期血流趋向零。该研究中斑块回声特征分为三类:(1)低回声斑块定义为富含脂质性斑块;(2)混合回声斑块,斑块后面没有声影,定义为脂质和钙化各占相近的比例;(3)高回声斑块伴有声影定义为斑块以钙化为主。随着颈动脉狭窄处血流速度的增加,血压压力下降。采用修正的柏努利(Bernoulli’s equation)公式计算出形成的压力梯度:△P=1/2×ρ×V~2:计算结果的单位是达因。单位换算成毫米汞柱后△P=4V~2,公式中△P的单位是mmHg。统计学分析采用探索分析对不同狭窄程度分组进行分析。颈内动脉狭窄的各个分组类型和斑块回声特征之间的关系采用相关分析。采用多变量逻辑回归分析方法对性别、血管危险因素和回声特点之间的关系进行分析,发现有统计学意义的影响因素。采用Kaplan-Meier生存分析模型分析颈内动脉狭窄各分组的死亡率。全部统计学均使用SPSS for Windows(SPSS有限公司,芝加哥,伊利诺斯)统计软件处理。P＜0.05代表统计学上有显著性差异。结果174位阳性病例存在颈动脉血流动力学异常(任何一侧狭窄程度＞60%)。其中,男性117,女性57;平均年龄74.8岁,最小年龄43岁,最大年龄95岁;348条颈内动脉中,狭窄小于60%的97条,狭窄在60%与79%之间的143条,狭窄在80%-99%之间的62条,颈总动脉或颈内动脉完全阻塞的46条。根据修正的柏努利(Bernoull i’s equation)公式:△P=4V~2(式中△P的单位是mmHg)计算出最狭窄处的压力梯度。轻度狭窄(＜60%)处的压力梯度的平均值右侧为3.13±2.09 mmHg,左侧为3.50±2.03 mmHg。中度狭窄(60-79%)处右侧为11.55±5.97 mmHg,左侧为11.58±5.01mmHg。重度狭窄(80-99%)处右侧为51.73±35.15 mmHg,左侧为48.83±28.58 mmHg。不同狭窄程度之间,压力梯度有明显差异。该论文对斑块的超声回声特征也进行了分析,结果显示低回声斑块和混合回声斑块,与神经症状的发生率成正比。重度狭窄(80-99%)的低回声斑块,比重度狭窄(80-99%)的混合回声斑块和高回声斑块伴有更高的神经症状。结论及意义症状性和无症状的严重颈动脉狭窄(80%-99%),血流速度有同样程度的增加,但是对无症状的严重颈动脉狭窄(80%-99%)患者长期超声随访发现,血流速度增加后数年,患者可以没有与脑中风和短暂性脑缺血发作相关的神经系统症状,而长期生存。对无症状长期生存的解释是局部压力梯度改变,不能在短时间内把一个稳定性斑块变为不稳定性斑块。因此,斑块的内部结构特征才是决定斑块破裂引起症状的关键因素。对斑块的回声特征进行分类分析,发现严重狭窄(80-99%)的低回声斑块,比严重狭窄(80-99%)的混合回声斑块和高回声斑块伴有更高的神经症状,进一步说明斑块的内部结构特征是决定斑块稳定性的关键因素。总之,该研究结果显示,颈动脉狭窄引起血流速度增加在狭窄处产生压力梯度,该压力梯度对斑块的稳定性产生影响,但是它不是造成中风等相关症状的决定性原因。斑块的内部结构特性才是决定斑块稳定性、造成中风等神经症状的决定性因素。所以,在超声随访中,既要重点检查斑块的回声特征和内部结构特征,又要检查狭窄引起的血流动力学改变。目的临床研究证明(1级,A水平),颈动脉内膜切除术是治疗症状性严重颈动脉狭窄的标准方法。尽管近几年,颈动脉支架置入术部分取代了颈动脉内膜切除术,然而,颈动脉内膜切除术仍然被认为是,预防症状性严重颈动脉狭窄引起的中风和死亡的金标准方法。到目前为止,前瞻性、随机对照的临床研究(RCTs),已经对颈动脉内膜切除术和颈动脉支架置入术进行了临床研究。结果显示,目前还不能确定通过选用颈动脉支架置入术,可以更好地预防和降低症状性严重颈动脉狭窄引起的中风率和死亡率。该论文的目的是分析有症状的系列患者接受常规颈动脉内膜切除术后,长期无中风生存率和早期再狭窄生存情况。方法该文收集了1996到1998年之间由血管外科医生完成的颈动脉内膜切除术102例。全部手术在全身麻醉下完成。颈动脉内膜切除术采用原位缝合术式或选择性应用涤纶补片血管成型术式。转流的标准是对侧颈内动脉完全闭塞和术前血管造影显示颈内动脉的解剖结构异常。术后患者接受1个月、3个月、6个月、12个月以及随后每半年一次的神经系统和颈动脉超声的随访检查。采用卡普兰-迈耶生存曲线对手术后长期随访的无中风生存率和早期再狭窄率进行分析。概率值≤0.05认为有统计学意义。结果围手术期神经系统并发症包括:3例短暂脑缺血发作(2.9%),3例非致残性中风(2.9%)。围手术期死亡1例(0.9%)。7例出现后期死亡。长期术后生存率分别为5年90%和12年65.7%。Kaplan-Meier生存曲线分析用于对各个危险因素进行分析,没有发现显著性差异。结论及意义对于有症状的严重颈动脉狭窄患者,原位缝合的常规颈动脉内膜切除术可以提供安全有效的治疗效果。利用卡普兰-迈耶生存曲线对长期随访的无中风生存率分析显示第5年的生存率为90%,第12年的生存率为65.7%。以前的研究结果显示有症状的颈内动脉狭窄,其5年的累积中风率是30%,该组病例的手术效果明显优于以上结果,5年内大约可以预防20%的缺血性中风。结论,依靠精确的手术技术,采用原位缝合的常规颈动脉内膜切除术同样可以取得良好的手术效果。颈动脉内膜切除术作为一种有效的、可以负担得起的、并被广泛使用的治疗方法,应该被推荐给更多的症状性颈动脉粥样硬化斑块狭窄患者。更多还原

【Abstract】 OBJECTIVES Intracranial artery embolism is one of the major mechanisms of ischemic stroke in patients with carotid atherosclerosis.Carotid atherosclerosis plaques cause 8%to 29%of all ischemic strokes.The aim of treatment for patients with carotid stenotic disease lies in decreasing the risk of disabling stroke or stroke-related death as consequences of thromboembolism.Nowadays,more specialists agree that only the degree of carotid stenosis is not sufficient to identify vulnerable patients at high risk to develop an acute ischemic stroke.Operating CEA on asymptomatic patients with severe carotid stenosis to prevent stroke demonstrates effectiveness but with less cost-effective.Study has demonstrated that in asymptomatic patients with severe carotid stenoses,85 operations were needed to prevent a single ischemic stroke.Therefore,it is an important topic how to identify vulnerable plaques with sever carotid stenosis that prone to rupture leading to ischemic stroke,so that we can prevent ischemic stroke effectively and accurately.Advanced ultrasound as a noninvasive method can diagnose hemodynamic compromise of carotid stenosis,as well as the characteristic of carotid plaques.Approximate 80%of patients in North America undergo CEA depending on US examination as the only preoperative imaging study.We design this longitudinal observational study to investigate the following objectives:(1) higher velocity at narrowing carotid has an effect on blood pressure gradient;(2) echogenicity of plaque influences the rate of ischemic stroke;(3) blood pressure gradient and plaque echogenicity influence the stability of carotid plaques.METHODS From January 2004 to December 2008,1408 patients with 2816 total carotid arteries under ultrasound screening,were analyzed in hemodynamic,echogenic,and pathological characteristics of carotid plaques,respectively.Definition of terminology is made for risk factors and neurologic symptoms,including:Hypertension,Diabetes mellitus, Hyperlipidemia,Smoking,Cardiac disease,Peripheral artery disease, Stroke,and TIA.The primary endpoints were defined as:(1) progressive asymptomatic stenosis progressed to occlusion;(2) occurrence of stroke;(3) Death by any cause in follow-up.B-mode,color flow images,and spectrum waveform were acquired for imaging of the carotid bifurcation and ICA three different views (acoustic windows) were used with the anterior,lateral and posterolateral.In each case,Color Doppler Flow Imaging(CDFI) and spectrum waveform techniques were used to estimate the degree of stenosis.Ultrasound criteria for ICA occlusion included the lack of color flow in the ICA and no signal available in spectrum waveform analysis,and detection of a diastolic flow towards zero in the common carotid artery.Echogenic characterization of plaques is classified into 3 different groups:(1) hypoechogenic plaque is fatty(soft) plaque;(2) mixed echogenic plaque without shadow is approximately the equal ratio of fatty and calcification in plaque;(3) hyperechogenic with shadow is calcified plaque.The blood pressure decreases across carotid stenosis as blood velocity increase.Pressure gradient is calculated by using modified form of Bernoulli’s equation:Δp=o.5 p V~2,unit in this form is dynes.Dynes is converted to mmHg,theΔP=4V~2;unit ofΔP in this form is mmHg.Statistical analysis Explore analysis was hired to investigate the pressure gradient of subtypes of stenosis.The relationships between subtype of the ICA stenosis and ICA plaque echogenicity were determined by correlation analysis.Multivariate logistic regression analysis was used to identify the vascular risk factors.The KaplanMeier survival curve was used to calculate the death rate of different carotid stenosis group.RESULTS 174 positive patients are identified with carotid hemodynamic abnormality(＞60%).Among 348 carotid arteries,117 male,57 female;mean age:74.8 years,range:52 years,from 43 to 95;97 carotid in＜60%,143 carotid in 60%-79%,62 in 80%-99%,46 in occlusion.According to modified form of Bernoulli’ s equation:ΔP=4V~2,unit in this form is mmHg.The calculated results of the pressure drop across at＜60%stenosis were 3.13±2.09 mmHg in right carotid,3.50±2.03 mmHg in left carotid.The 60%-79%stenosis were 11.55±5.97 mmHg in right carotid and 11.58±5.01mmHg in left carotid. The 80%-99%stenosis were 51.73±35.15 in right carotid and 48.83±28.58 in left carotid.There were significant diffenrence between subtype of pressure gradient.The result of echogenicity of plaques demonstrated that hypoechogenic plaque had much more positive correlation with cerebrovascular events than mixed and hyperechogenic plaques.CONCLUSIONS and SIGNIFICANCES In symptomatic and asymptomatic severe carotid stenosis(80%-99%),the flow velocity is increased in the same situation.However during the long term follow-up with ultrasound for asymptomatic severe carotid stenosis(80%-99%),the positive patients can survive for several years without symptoms of stroke and TIA.If the pressure gradient is a critical factor to rupture the plaques,the symptoms should emerge within a short period under extremes values.The explanation of long-term asymptomatic survival is that the extreme situation can not change a stable plaque into a unstable plaque.Therefore,the internal characteristics of a plaque are the critical factor to rupture plaques causing symptoms.By analyzing the property of plaque echogenicity in different group,the hypoechogenic plaques in severe carotid stenosis group were accompanied by higher frequent neurologic symptoms than mixed and hyperechogenic plaques in the same carotid stenosis.This result proved further evidence that the internal property of plaques were the critical factor to determine the plaque stability.In summary,the result of this study had demonstrated that higher flow velocity which was caused by carotid stenosis produced blood pressure gradient at carotid stenosis.This pressure gradient influence the plaque stability,however it was not the dominant factor in causing neurologic symptoms.The internal characteristic rather than the external factors of plaque should be the dominant determinant to rupture plaque which associates with ischemic stroke and related symptoms.The echogenic plaque property has demonstrated that hypoechogenic plaquend are more prone to cause cerebral symptoms than mixed echogenic plaque and hyperechogenic calcified plaque. Therefore,it must be bear in mind that carotid ultrasound examination should investigate both the internal characteristic of plaque and external hemodynamic abnomal at the narrowest stenosis site. OBJECTIVES Carotid endarterectomy(CEA) is supported by clinical evidence (Class 1 and Level A) as the standard treatment of severe carotid stenosis in symptomatic patients.Although,it is partly replaced by popular Carotid Artery Stenting(CAS) recently,however,CEA is still regarded as a golden standard procedure in reducing the long-term risk of stroke and mortality due to severe carotid stenosis in symptomatic patients.So far,prospective,randomized clinical trials(RCTs) have compared the effect of Carotid Artery Stenting(CAS) and Carotid Endarterectomy(CEA).The results demonstrated that adoption of Carotid Artery Stenting(CAS) with the hope of decreasing postoperative stroke or death rate is not warranted at current time.The purpose of this study is to analyze long-term stroke-free survival and early restenosis survival in a consecutive series of patients who underwent CEA for symptomatic carotid disease.METHODS Patient data were retrospectively collected for all patients who underwent conventional CEA with primary closure or patch for symptomatic severe carotid disease performed by a vascular surgeon.All included CEAs were performed from 1996 to 1998 in 102 patients.All CEA were performed under general anesthesia. Most patients had neurological follow-up and duplex ultrasound at 1,3,6,and 12 months,and biannually thereafter.Kaplan-Meier curve is used to analyses long-term free-stroke survival and early restenosis survival.Probability values＜0.05 are considered statistically significant.RESULTS Perioperative neurologic complications included 3 transient ischemic attacks(TIAs)(2.9%),3 nondisabling strokes(2.9%).There was one 30-day death from this study(0.9%),7 patients with late death.Long term free-stroke survival rate was 90%and 65.7%at 5 and 12 years,respectively.Kaplan-Meier curve was used for every risk factor,but no significant difference was obtained.CONCLUSIONS Conventional CEA with primary closure proved safe and effective outcome in a series of patients with symptomatic severe carotid disease representing the typical population of daily clinical practice.Long term free-stroke survival rate was 90%and 65.7%at 5 and 12 years,respectively.It is not inferior to previous studies,which showed the accumulate stroke rate of symptomatic carotid stenosis without surgical intervention with 30%at 5 years.The result of this study demonstrated that it could prevented 20%ischemic stroke approximately.In this study,conventional CEA proved safe and effective long term effect on preventing stroke under experienced vascular surgeon.Carotid endarterectomy,as an effective,affordable,widely applicable treatments should be recommended for symptomatic patients.更多还原