【作者】 刘娟；

【导师】 周华东；

【作者基本信息】 第三军医大学 ， 神经病学， 2013， 博士

【摘要】 在全球老龄化的今天，脑卒中以其高发病率、高致残率、高死亡率成为威胁人类健康的重要疾病。缺血性脑卒中占所有卒中人群的75%～85%，而颈动脉粥样硬化性狭窄是引起缺血性脑卒中的主要病因之一，20%以上的缺血性卒中是由于颅外颈动脉粥样硬化性狭窄所致。治疗颈动脉狭窄可以降低卒中风险，减少卒中相关的死亡率。颈动脉内膜剥脱术(carotid endarterectomy，CEA)是治疗颈动脉狭窄的金标准，在预防卒中和死亡风险方面显示出比药物治疗更明显的优势。近年来，随着神经影像学技术的迅速发展，颈动脉支架置入术(carotid artery stenting，CAS)日渐成为治疗颅外颈动脉狭窄、预防缺血性卒中的一种简单、有效、微创的方法，并有望成为替代CEA的治疗方式。但是，既往多项临床试验结果显示，CAS围手术期主要并发症(卒中、心肌梗塞、死亡)发生率并不低于CEA，因此，通过各种可干预因素降低CAS围手术期并发症仍是目前亟待解决的问题。对CAS围手术期主要不良事件进行风险评价有助于对患者进行术前术中的评估及干预。既往针对CAS的临床研究的多选择对CEA的高危患者实施CAS并进行风险评估，且纳入的均为年龄、心脑血管病史、病变特征等不可控制因素。有研究显示，CAS术中发生的低血流动力学改变、血管痉挛、急性支架内血栓、斑块脱垂等可控制因素与围手术期心脑血管事件发生有关，因此，对上述可控制因素进行干预，有助于降低围手术期不良心脑血管事件的发生。本研究旨在通过对CAS患者进行围手术期随访研究，寻找CAS围手术期不良心脑血管事件发生的独立风险因素，建立风险评分模型，并对其中的可干预因素的防治进行探讨。第二章颈动脉支架置入围手术期心脑血管事件发生的风险评价目的：分析CAS围手术期主要不良心脑血管事件(major adverse cardiac andcerebrovascular events，MACCE)包括短暂性脑缺血发作、卒中、心肌梗塞、死亡的危险因素，并建立风险评分模型，评价该模型的预测效力。对象和方法：于2010.1-2013.6期间收集在第三军医大学附属大坪医院神经内科住院行颈动脉支架置入的患者。入组后收集临床基线数据、影像学资料及术中基本情况,对入组患者进行围手术期30d的随访，按照是否发生MACCE进行分组，对围手术期MACCE的发生进行危险因素分析，并建立评分模型，通过绘制受试者工作特征曲线(receiveroperating characteristic curve，ROC曲线)并计算曲线下面积(area under curve, AUC)评价该评分模型的预测效力。结果：1.本研究入组403名患者并完成围手术期随访，平均年龄为66.73±7.03岁。围手术期MACCE发生33例，占入组患者8.19%，其中脑卒中、心肌梗塞、死亡发生16例，占入组患者的3.97%。2.多因素Logistic回归分析显示CAS围手术期MACCE发生的独立危险因素是：(1)年龄≥70岁(OR4.997,95%CI1.633-15.290)；(2)溃疡型斑块(OR2.899,95%CI1.214-6.924)；(3)重度狭窄(OR3.472,95%CI1.141-10.566)；(4)双侧颈动脉支架置入(OR5.007,95%CI1.462-17.151)；(5)CAS后低血流动力学改变(OR5.792,95%CI1.226-27.369)。3.本研究建立的CAS围手术期MACCE发生的回归方程为：LOG(MACCE发生概率)=-8.992+1.609×年龄≥70岁+1.064×溃疡型斑块+1.245×重度狭窄+1.611×双侧颈动脉支架+1.757×HD。4.利用该回归方程建立危险评分表，以危险评分为预测变量来预测MACCE的风险，绘制ROC曲线，计算出的AUC为0.875(p<0.001,95%CI0.825-0.925)。结论：CAS围手术期MACCE发生的独立危险因素是(1)年龄≥70岁；(2)溃疡型斑块；(3)重度狭窄；(4)双侧颈动脉支架置入；(5)CAS后低血流动力学改变。其中，CAS后低血流动力学改变是术中术后的可干预危险因素。以上述危险因素建立的评分模型有助于对CAS围手术期MACCE的高危患者进行评估及早期防治。第三章颈动脉支架置入低血流动力学的改变及心脏临时起搏器的应用目的：分析CAS后低血流动力学(hemodynamic depression，HD)改变的相关因素，并对经静脉心脏临时起搏器在改善CAS后HD及围手术期MACCE的作用进行探讨。对象和方法：于2010.1-2013.6期间收集在第三军医大学附属大坪医院神经内科住院行CAS的患者。入组后收集患者临床基线数据、影像学特征及术中操作等资料，并进行围手术期30d的随访。按照是否发生CAS后HD进行分组，对HD的发生进行多因素Logistic回归分析，建立回归方程，评价各因素作用大小。选择性对存在缓慢性心律失常或HD的高危患者使用保护性心脏临时起搏器，评价HD的发生、术后起搏器相关并发症及围手术期MACCE发生情况。结果:1．本研究入组403名患者并完成围手术期随访，241例(58.90%)患者发生HD。其中，心动过缓合并血压下降的176例(73.03%)，单纯心动过缓36(14.94%)例，单纯血压下降29例(12.03%)；2． CAS低血流动力学发生的独立相关因素是:钙化斑块(OR7.863,95%CI3.221-19.199)、偏心型斑块(OR2.744,95%CI1.659-4.538)、重度狭窄(OR1.701，95%CI1.006-2.878)、病变长度(≥15mm)(OR5.469,95%CI2.753-10.866)、双侧颈动脉支架(OR6.921,95%CI1.338-35.795)、锥形支架(OR0.389,95%CI0.195-0.774)、球囊预扩(OR4.985,95%CI1.371-18.126)。3．以上7个相关危险因素对CAS低血流动力学发生的影响作用可以通过以下回归方程表示: Log(HD发生概率)=-1.152+2.062×钙化斑块+1.009×偏心性斑块+0.531×重度狭窄+1.699×病变长度(≥15mm)+1.935×双侧颈动脉支架–0.945×锥形支架+1.606×球囊预扩，影响作用由大到小为：双侧颈动脉支架＞球囊预扩＞钙化斑块＞病变长度(≥15mm)＞锥形支架＞偏心型斑块＞重度狭窄，其中锥形支架为负相关因素；4.在241例发生CAS低血流动力学改变的患者中，围手术期MACCE发生31例，占HD组患者总数的12.86%；5.38例HD高危患者于CAS术前保护性安置经静脉心脏临时起搏器，占所有CAS患者的9.43%。术中无患者出现心脏骤停、晕厥、TIA，无起搏器相关并发症及围手术期MACCE发生。结论：CAS低血流动力学改变与围手术期MACCE发生有关，钙化斑块、偏心型斑块、重度狭窄、双侧颈动脉支架置入、球囊预扩等与HD发生呈正相关，锥形支架与HD发生呈负相关。对缓慢性心律失常或HD高危患者进行保护性安置临时心脏起搏器可以减少围手术期MACCE的发生。更多还原

【Abstract】 The world’s population is aging, and stroke has become a serious disease threatinghuman health with high incidence, high morbidity and high mortality. Ischemic strokeaccounts for75%~85%of all stroke population, and extracranial carotid artery stenosis isone of the most importment causes of ischemic stroke. More than20%of ischemic stroke isdue to extracranial carotid atherosclerotic stenosis. Treatment for carotid stenosis canreduce the risk of stroke and stroke-related mortality.For the time being, carotid endarterectomy(CEA)remains the gold standard for thetreatment of carotid stenosis，which shows more significant advantages than medicaltherapy in prevention of stroke. In the last few years, carotid artery stenting (CAS) hasemerged as a possible alternative to CEA for the management of carotid stenosis because ofits effectiveness and less invasive nature of the procedure. However，previous clinical trialshave shown that perioperative complications as stroke, myocardial infarction and death inCAS is not less than CEA. It is urgent to reduce perioperative major adverse cardiac andcerebrovascular events(MACCE)of CAS through some interventional factors.A risk assessment for MACCE is benefical for patients with CAS. Some clinical studywere mainly to evaluate the risk factors of selected high-risk patients with CEA and certainuncontrollable factors such as age, past medical history and lesion characteristics were onlyconsidered. It was reported that such intraoperative complications as vascular spasm,hemodynamic depression(HD) may result in catastrophic events such as stroke or death.Prompt recognition and rapid evaluation of these complications are crucial for good patientoutcome.The aim of the present study was to identify independent risk factors to predictperioperative MACCE for CAS patients. We also aimed to analysis the value of treatmenton certain associated controllable risk factors on the aspect of the prevention of MACCE. Part one Risk modeling evaluation of major adverse events after carotid arterystentingObjectives: To identify independent risk factors to predict perioperative major adversecerebral and cardiovascular events for CAS patients and establish risk evaluation model.Methods: Consecutive patients treated with a standardized CAS procedure wereenrolled in the present study. All patients included underwent independent neurologicalevaluation before and after the procedure and at30days. The rates of transient ischemicattack, stroke, myocardial infarct and death were recorded. Relative regression model wasestablished to evaluate risk factors of perioperative major adverse cardiac andcerebrovascular events.Results:1. A total of403subjects treated with CAS were enrolled into the study at baseline(mean age66.73years, SD7.03), MACCE rate was8.19%(n=33). Whereas the overallstroke, myocardial infarction and death rate at30days was3.97%.2. Multiple regression analysis showed that the following factors significantlypredicted the30-day risk of treatment-relaterd MACCE:(1) age of70or older (OR4.997,95%CI1.633-15.290);(2) ulcerative plaque (OR2.899,95%CI1.214-6.924);(3) severecarotid stenosis (OR3.472,95%CI1.141-10.566);(5) bilateral carotid artery stenting (OR5.007,95%CI1.462-17.151);(6) hemodynamic depression after CAS(OR5.792,95%CI1.226-27.369).3. MACCE risk prediction model was established by the following formula:Log(MACCE prediction probability)=-8.992+1.609×(age of70or older)+1.064×(ulcerative plaque)+1.245×(severe carotid stenosis)+1.611×(bilateral carotid arterystenting)+1.757×(hemodynamic depression).4. A risk score system was generated using Arabic numerals on the basis of statisticalanalysis of each of the aforementioned variables to grade the individual patient risk ofMACCE. The goodness of the score generated is shown by the receiver-operatorcurves(ROC) of the learning and testing and area under curve(AUC) is0.875(p<0.001,95%CI0.825-0.925)Conclusions: Following factors significantly predicted the30-day risk of MACCEof CAS: age of70or older，ulcerative plaque，severe carotid stenosis，bilateral carotid artery stenting， hemodynamic depression after CAS. Among above five factors，hemodynamic depression was controllable factor. The established risk score system seemsto be a usefule tool to help predict MAACE after CAS.Part two Associated factors of hemodynamic depression after carotid arterystenting and application of temporary cardiac pacemakerObjectives: To analysis associated factors of HD after CAS. We also aimed to analysisthe effectiveness of prophylactically use of a transvenous temporary cardiac pacemaker tomanage HD.Methods: Consecutive patients treated with a standardized CAS procedure wereenrolled in the present study. All patients included underwent independent neurologicalevaluation before and after the procedure and at30days. Relative regression model wasestablished to evaluate risk factors of intra-or post-operative HD. Cardiacpacemaker-related complication and incidence of perioperative MACCE were analysedfor the patients treated with transvenous temporary cardiac pacemaker group.Results:1. A total of403subjects treated with CAS were enrolled into the study, and incidenceof HD intra-or post-operative HD was58.90%(n=241). Bradycardia combined withhypotension occurred in176patients (73.03%). Isolated bradycardiawithout hypotension occurred in36patients(14.94%). Isolated hypotension withoutbradycardia occurred in29patients(12.03%)。2. Multiple regression analysis showed that the following factors were significantlyassociated with HD:(1) calcified plaque (OR7.863,95%CI3.221-19.199);(2) eccentricplaque(OR2.744,95%CI1.659-4.538);(3) severe carotid stenosis(OR1.701,95%CI1.006-2.878);(4) lesion length(≥15mm)(OR5.469,95%CI2.753-10.866);(5) bilateralcarotid artery stenting(OR6.921,95%CI1.338-35.795);(6) tapered stenting(OR0.389,95%CI0.195-0.774);(7) balloon pre-dilation(OR4.985,95%CI1.371-18.126)；3.Associated risk prediction model was established by the following formula: Log(HDprediction probability)=-1.152+2.062×calcified plaque+1.009×eccentric plaque+0.531×severe carotid stenosis+1.699×lesion length (≥15mm)+1.935×bilateral carotidartery stenting–0.945×tapered stenting+1.606×balloon pre-dilation. The standardizedregression coefficient of above seven independent risk factors can be in accordance with the order of value as follows: bilateral carotid artery stenting＞balloon pre-dilation＞calcifiedplaque＞lesion length (≥15mm)＞tapered stenting＞eccentric plaque＞severe carotidstenosis.4. MACCE rate in HD group was12.86%which was significantly higher than innon-HD group(p＜0.001);5. Among403patients enrolled，38cases(9.43%)accepted prophylactic placement oftransvenous temporary cardiac pacemaker. No cardiac arrest,syncope and TIA occurredintra-operative of CAS and there were no pacemake-related complications andperioperative MACCE.Conclusions: HD is correlated with perioperative MACCE of CAS. Calcified plaque,eccentric plaque, severe carotid stenosis, lesion length, bilateral carotid artery stenting,tapered stenting and balloon pre-dilation were associated with the occurrence of HD.Prophylactic placement of transvenous temporary cardiac pacemaker for patients at highrisk of HD can reduced perioperative MACCE.更多还原