CYP2C19基因多态性与颅内动脉瘤支架置入术后临床预后的相关性分析研究
本文选题:颅内动脉瘤 + 支架 ; 参考:《首都医科大学》2017年博士论文
【摘要】:背景:颅内动脉瘤作为一种危害人类生命健康的严重脑血管出血性疾病,许多年来关于其最优化治疗方式的选择一直饱受争议且得不到定论。尽管随着医疗材料技术的进步,颅内支架系统目前已广泛应用于多种类型的复杂颅内动脉瘤(如宽颈、夹层、梭型动脉瘤等),众多患者得到了较为积极的治疗。但是,支架的致血栓特性也限制了应用。现阶段,口服双重抗血小板药物,尤其是氯吡格雷的广泛应用,使得支架内血栓形成的概率大大的降低,缓解了很多患者的病痛之苦。然而,有相当数量的患者在服用标准剂量抗血小板药物——氯吡格雷后,仍旧出现心脑血管意外事件(主要为缺血性事件)的发生,这种情况通常被认为产生了“氯吡格雷抵抗”。目前,已有研究证实基因表达水平(主要有CYP2C19多态性等)为影响氯吡格雷抵抗与否的一项非常重要的因素。但是,其在颅内动脉瘤支架治疗及预后检测方面的相关性研究仍然相对缺乏。目的:本次研究旨在探索CYP2C19基因多态性与颅内动脉瘤支架置入术后临床预后及抗血小板药物疗效之间的相关性。方法:前瞻性登记入组于2014年9月至2015年10月期间,在首都医科大学附属北京天坛医院神经介入科住院,并且接受颅内支架系统置入治疗的颅内动脉瘤患者,并且详细记录了所有入组患者的临床资料、影像学信息及预后随访资料等数据。提取所有入组患者的静脉血液样本,并对标本进行CYP2C19基因多态性检测;对所有入组的患者分别于抗血小板药物服用前、手术前、术后或随访期间,采用血栓弹力图(thrombelastography,TEG)技术对血小板功能进行检测,并且根据检测结果评估抗血小板药物(尤其是氯吡格雷)的疗效。所有患者均于手术后48h内接受核磁共振弥散加权成像(MRI-DWI)及灌注加权成像(MRI-PWI)检查,以观察和鉴别是否有新发或急性颅内梗塞灶。制订临床终点事件为颅内缺血性事件或全身出血性事件,并对所有入组患者进行术后为期3个月的临床随访,详细记录随访期间入组患者的m RS评分、预后及各个临床终点事件的发生情况。对所得数据进行统计学检测,分析CYP2C19基因多态性、血小板功能检测结果与颅内动脉瘤支架置入术后临床结局的相关性。结果:共计215例颅内动脉瘤患者于首都医科大学附属北京天坛医院神经介入科接受颅内支架系统置入治疗,并登记入组于数据库中。其中,男性患者有86例(40.0%),女性患者有129例(60.0%),入组患者年龄范围为18岁至79岁,平均年龄为52.3±10.2岁。本次研究共计使用275个颅内各类型支架治疗243个颅内动脉瘤,包括170个前循环动脉瘤及73个后循环动脉瘤。经过术后即刻脑血管造影检查,在215例动脉瘤患者中,有171例(79.5%)得到了完全栓塞;有25例(11.6%)为近全栓塞;有19例(8.9%)为部分栓塞或仅是支架覆盖动脉瘤。在215例入组病例中,广泛代谢组(extensive metabolizers,EM,CYP2C19*1/*1基因型)病例有76(35.3%)例;中间代谢组(intermediate metabolizers,IM,CYP2C19*1/*2,*1/*3基因型)有108(50.3%)例;缓慢代谢组(poor metabolizers,PM,CYP2C19*2/*2,*2/*3,*3/*3基因型)有31(14.4%)例。在总计215例入组病例中,有68例(31.6%)病例通过血栓弹力图被检测到存在氯吡格雷药物抵抗;有69例患者(32.1%,69/215)在术后及随访期间经检查发现与支架释放部位相关的颅内缺血性并发症;有20例患者(9.3%,20/215)经检查发现出现颅内或全身系统的出血性并发症。将EM组患者分别与IM组患者及PM组患者进行统计学对比,可以发现,EM组患者发生术后颅内缺血性事件的概率明显低于IM组患者(p=0.02)和PM组患者(p=0.027)。通过单因素及多因素回归分析发现,CYP2C19慢代谢等位基因(*2、*3)携带与否(p=0.032,OR=2.07,95%CI=1.063-4.030)及服药后出现氯吡格雷抵抗情况(p=0.047,OR=0.534,95%CI=0.287-0.993)可有较高几率伴随颅内动脉瘤支架置入术后颅内缺血性并发症的发生;而未携带CYP2C19慢代谢等位基因可以伴随颅内及全身系统出血性事件的发生(p=0.002,OR=0.205,95%CI=0.075-0.557);后循环动脉瘤(p=0.038,OR=3.856,95%CI=1.076-13.822)、颅内动脉瘤破裂史(p=0.001,OR=0.078,95%CI=0.019-0.329)、携带2个CYP2C19慢代谢等位基因即PM组(p=0.001,OR=9.058,95%CI=2.366-34.682)与较差的临床预后具有明显的统计学相关性。结论:CYP2C19基因多态性可以影响接受颅内支架系统置入的颅内动脉瘤患者口服抗血小板药物氯吡格雷的疗效,这可能会在一定程度上导致一些出血性或缺血性并发症的发生;并且CYP2C19基因多态性可以作为颅内动脉瘤支架置入术后缺血性及出血性临床终点事件的风险预测因素。
[Abstract]:Background: intracranial aneurysm is a serious cerebral vascular hemorrhagic disease which endangers human life and health. The selection of optimal treatment methods has been disputed for many years. Although with the progress of medical materials technology, the intracranial stent system has been widely used in many types of complex intracranial aneurysms. Many patients have been treated more actively, such as wide neck, interlayer and spindle aneurysm. However, the thrombus characteristics of the scaffold are also limited. At this stage, the extensive use of oral antiplatelet drugs, especially clopidogrel, makes the probability of thrombosis in the stent greatly reduced and alleviates the pain of many patients. However, a considerable number of patients, after taking the standard dose antiplatelet drug - clopidogrel, still have the occurrence of cardiac and cerebrovascular accidents (mainly ischemic events), which are usually considered to produce "clopidogrel resistance". Currently, the level of gene expression (mainly CYP2C19 polymorphism, etc.) has been confirmed. It is a very important factor affecting the resistance of clopidogrel. However, the correlation of the correlation between the stent therapy and the prognosis of intracranial aneurysms is still relatively lack. Objective: This study aims to explore the relationship between CYP2C19 gene polymorphism and the clinical prognosis of intracranial aneurysm after stent implantation and the effect of antiplatelet drugs. Methods: the prospective registration group was hospitalized in the Neurointerventional Department of Beijing Tiantan Hospital, Capital Medical University, from September 2014 to October 2015, and received intracranial aneurysm patients treated with intracranial stent system, and the clinical data, imaging information and prognosis of all the patients were recorded in detail. The venous blood samples of all the patients were extracted and the CYP2C19 gene polymorphisms were detected. The platelet function was detected by thrombelastography (TEG) technique before and after the operation, before the operation, and during the follow-up period. The results were evaluated for antiplatelet drugs (especially clopidogrel). All patients received NMR diffusion weighted imaging (MRI-DWI) and perfusion weighted imaging (MRI-PWI) within 48h after surgery to observe and identify new or acute intracranial infarction. Clinical endpoints were developed for intracranial ischemic events or systemic hemorrhage. All the patients were followed up for 3 months. The m RS score, prognosis and the occurrence of various clinical endpoints were recorded during the follow-up period. The data were statistically tested, the CYP2C19 gene polymorphism, the blood plate function test and the intracranial aneurysm stent implantation were analyzed. Results: a total of 215 cases of intracranial aneurysms were implanted in the Neurointerventional Department of the Beijing Tiantan Hospital of Capital Medical University, which were treated with intracranial stent system and registered in the database. Among them, 86 cases (40%) were male patients and 129 cases (60%) in female patients. The age range of the patients in the group was 18 to 79. The average age was 52.3 + 10.2 years. A total of 275 intracranial stents were used to treat 243 intracranial aneurysms, including 170 anterior circulation aneurysms and 73 posterior circulating aneurysms. After immediate cerebral angiography after operation, 171 cases (79.5%) were completely embolized in 215 patients with aneurysm; 25 (11.6%) were nearly complete. Embolization; 19 cases (8.9%) were partially embolized or only stent covered aneurysms. Among the 215 cases, 76 (35.3%) cases were in the extensive metabolizers, EM, CYP2C19*1/*1 genotype, 108 (50.3%) in the intermediate metabolism group (intermediate metabolizers, IM, CYP2C19*1/*2, *1/*3 genotype); the slow metabolism group (poor metabolize) There were 31 (14.4%) cases of RS, PM, CYP2C19*2/*2, *2/*3, *3/*3 genotypes. In a total of 215 cases, 68 (31.6%) cases were detected with clopidogrel resistance through a thrombus map; 69 patients (32.1%, 69/215) were examined after and followed up for intracranial ischemic complications associated with the release site of the stent; 20 Patients (9.3%, 20/215) were found to have intracranial or systemic hemorrhagic complications after examination. Compared with group EM and group PM, the probability of intracranial ischemic events in group EM patients was significantly lower than that of group IM (p=0.02) and PM group (p=0.027). By single factor and more, the patients in group EM were found to be more likely to have hemorrhagic complications. Factor regression analysis found that the CYP2C19 slow metabolic allele (*2, *3) carrying or not (p=0.032, OR=2.07,95%CI=1.063-4.030) and the presence of clopidogrel (p=0.047, OR=0.534,95%CI=0.287-0.993) after taking the drug (p=0.047, OR=0.534,95%CI=0.287-0.993) could have a higher risk of intracranial ischemic complications following the stent placement of intracranial aneurysm, but not CYP2C19 slow. Metabolic alleles can be associated with intracranial and systemic hemorrhagic events (p=0.002, OR=0.205,95%CI=0.075-0.557); posterior circulating aneurysm (p=0.038, OR=3.856,95%CI=1.076-13.822), intracranial aneurysm rupture history (p=0.001, OR=0.078,95%CI=0.019-0.329), and PM group (p=0.001, OR=9.058,95%CI=) carrying 2 CYP2C19 slow metabolic alleles. 2.366-34.682) has a significant statistical correlation with poor clinical prognosis. Conclusion: CYP2C19 gene polymorphism may affect the efficacy of oral antiplatelet drug clopidogrel in intracranial aneurysm patients receiving intracranial stent implantation, which may cause some hemorrhagic or ischemic complications to a certain extent. The CYP2C19 gene polymorphism can be used as a predictor of ischemic and hemorrhagic clinical endpoint events after stent placement for intracranial aneurysms.
【学位授予单位】:首都医科大学
【学位级别】:博士
【学位授予年份】:2017
【分类号】:R743.3
【相似文献】
相关期刊论文 前10条
1 寿之人;电解可脱性弹簧圈栓塞治疗颅内动脉瘤的护理[J];浙江临床医学;2002年06期
2 梁美馨,肖绍文;电解可脱性弹簧圈栓塞治疗颅内动脉瘤31例[J];广西医科大学学报;2004年04期
3 余光琴;梁玉红;;多发颅内动脉瘤同时夹闭1例分析[J];中国误诊学杂志;2008年12期
4 ;颅内动脉瘤家族史与早发破裂无关?[J];实用心脑肺血管病杂志;2009年02期
5 赵学喜,李慧勤,巩维进;家族性颅内动脉瘤破裂3例[J];中国实用内科杂志;2000年03期
6 姜智南,黄求理,宋侃侃,周景义;机械可脱性螺旋圈栓塞治疗颅内动脉瘤[J];浙江临床医学;2000年05期
7 江宝柱,牛小敏;电解可脱式弹簧圈栓塞颅内动脉瘤的新进展[J];临床医药实践;2003年01期
8 王利军,史耀亭,张新中,周文科,周杰,周国胜;颅内动脉瘤诊断和治疗时机分析[J];中国误诊学杂志;2003年07期
9 王志刚,丁璇,贺红卫,王成伟,庞琦;电解可脱性微弹簧圈栓塞治疗颅内动脉瘤[J];山东大学学报(医学版);2004年04期
10 王志刚,丁璇;颅内动脉瘤[J];山东医药;2004年30期
相关会议论文 前10条
1 金国良;;颅内动脉瘤夹闭术5例报告[A];2006年浙江省神经外科学术会议论文汇编[C];2006年
2 曾博;范良好;谭显西;钟鸣;;三维DSA在颅内动脉瘤治疗中的价值[A];2006年浙江省神经外科学术会议论文汇编[C];2006年
3 孙伟军;王义荣;朱先理;方兵;杨树旭;牛焕江;李新伟;;颅内动脉瘤的手术治疗[A];2009年浙江省神经外科学术年会论文汇编[C];2009年
4 孙堂胜;魏世辉;;伴有眼部表现的颅内动脉瘤初探[A];中华医学会神经外科学分会第九次学术会议论文汇编[C];2010年
5 钱硕;鲁晓杰;季卫阳;;70岁以上老年人破裂颅内动脉瘤的栓塞治疗[A];中华医学会神经外科学分会第九次学术会议论文汇编[C];2010年
6 孙晓川;夏小辉;;未破裂颅内动脉瘤的处理[A];中华医学会神经外科学分会第九次学术会议论文汇编[C];2010年
7 伍聪;贺民;赵中新;李天贵;张瑜;;颅内动脉瘤再破裂风险的研究[A];中华医学会神经外科学分会第九次学术会议论文汇编[C];2010年
8 邢国祥;黄清海;许奕;刘建民;;颅内动脉瘤的大小和部位与破裂的关系[A];中华医学会神经外科学分会第九次学术会议论文汇编[C];2010年
9 丁小灵;任明山;李淮玉;何玉圣;邓克学;;颅内动脉瘤103例临床分析[A];2010中国医师协会中西医结合医师大会摘要集[C];2010年
10 孙晓川;夏小辉;朱继;张晓冬;吕发金金;;未破裂颅内动脉瘤的处理及临床随访分析[A];中国医师协会神经外科医师分会第六届全国代表大会论文汇编[C];2011年
相关重要报纸文章 前10条
1 梁兆松;人脑中的定时炸弹——颅内动脉瘤[N];中国中医药报;2008年
2 吴中学 刘爱华;未破裂颅内动脉瘤的治疗决策[N];健康报;2007年
3 第二军医大学长海医院神经外科 杨鹏飞;颅内动脉瘤治疗思路要变?[N];健康报;2009年
4 朱凤霞;山铝医院成功治疗颅内动脉瘤[N];淄博日报;2011年
5 印红霞;颅内动脉瘤须及时治疗[N];家庭医生报;2007年
6 袁波 龙先瑜;颅内动脉瘤 凶险的“地雷”[N];大众卫生报;2004年
7 记者 胡德荣 通讯员 邱志涛;血管重建术治颅内动脉瘤效果显著[N];健康报;2011年
8 刘建民 张永巍 (上海长海医院临床神经医学中心主任、神经外科主任 刘建民);颅内动脉瘤[N];文汇报;2009年
9 冯琳;陈志;联合手术治愈巨型颅内动脉瘤[N];中国医药报;2005年
10 匡远深;专用支架栓塞颅内动脉瘤[N];中国医药报;2005年
相关博士学位论文 前10条
1 杨扬;螺旋CT血管造影和数字减影造影对颅内动脉瘤诊断及评估的比较研究[D];浙江大学;2016年
2 张振;探寻颅内动脉瘤新易感基因的研究[D];天津医科大学;2016年
3 葛慧剑;CYP2C19基因多态性与颅内动脉瘤支架置入术后临床预后的相关性分析研究[D];首都医科大学;2017年
4 顾宇翔;颅内动脉瘤形成的相关因素研究[D];复旦大学;2005年
5 蒲朝霞;主动脉内径和弹性改变与颅内动脉瘤的相关性研究[D];浙江大学;2011年
6 沙龙金;炎症相关基因多态性与168例颅内动脉瘤易感性的关联研究[D];南方医科大学;2014年
7 伍刚;血管平滑肌雌激素受体表达与颅内动脉瘤相关性研究[D];中国人民解放军军医进修学院;2007年
8 陈文华;颅内动脉瘤的诊断、治疗和疗效评价的比较影像学研究[D];南京医科大学;2009年
9 葛明旭;颅内动脉瘤致病基因筛查及血管内介入治疗的研究[D];山东大学;2007年
10 朱文焕;颅内动脉瘤动物模型的建立及发病机制的研究[D];苏州大学;2012年
相关硕士学位论文 前10条
1 索苗苗;1、LncRNA AL110200促进动脉粥样硬化炎症作用及机制研究 2、Kallikrein基因遗传变异与国人散发性颅内动脉瘤的关联性研究[D];北京协和医学院;2013年
2 宋洋;颅内动脉瘤破裂急性期治疗方案的Meta-分析[D];山西医科大学;2015年
3 宗华;120例颅内动脉瘤血管内介入治疗的临床研究[D];山西医科大学;2015年
4 薛文涛;血管内栓塞治疗颅内动脉瘤的临床资料分析[D];青岛大学;2015年
5 马刘佳;颅内动脉瘤破裂早期血管内栓塞治疗临床分析[D];延安大学;2015年
6 张利通;天津地区颅内动脉瘤危险因素相关基因多态性的研究[D];天津医科大学;2015年
7 张腾;颅内动脉瘤破裂的危险因素分析[D];济南大学;2015年
8 何雪峰;高级别颅内动脉瘤患者保守治疗12h后再手术对预后的影响[D];山西医科大学;2016年
9 康慧斌;颅内动脉瘤破裂临床风险因素分析[D];首都医科大学;2016年
10 鲍跃;3D-CTA与3D-DSA诊断及测量颅内动脉瘤的对比分析[D];吉林大学;2016年
,本文编号:1864550
本文链接:https://www.wllwen.com/yixuelunwen/shenjingyixue/1864550.html