【作者】 付刚；

【导师】 郑杨；

【作者基本信息】 吉林大学 ， 内科学， 2014， 博士

【摘要】 IC53基因自身抗体与心力衰竭预后关系的研究背景：心力衰竭是大多数心脏疾病的终末临床表现。心衰的发病机制、病理生理变化十分复杂，目前仍未完全阐明。越来越多的研究证实，自身免疫反应参与了心衰的病理生理过程，在心衰的发生发展中起着很重要的作用。心衰病人外周血中可以检测到多种抗心脏自身抗体，这些自身抗体与心衰有着密切关系。本研究主要检测扩张性心肌病、冠心病心衰病人中IC53基因自身抗体水平，分析IC53基因自身抗体对心血管终点事件的影响以及与心衰预后的关系。旨在为临床预测、诊断及治疗心力衰竭提供新的诊断试剂或药物作用新靶点。方法：1.研究样本包含特发性扩张型心肌病心衰病人177例，冠心病心衰病人588例。2.以合成肽作为抗原，应用酶联免疫吸附测定技术检测两组受试者血浆中IC53自身抗体。3.平均随访4年，终点事件是心源性死亡和猝死。4.应用Cox回归分析和Kaplan-Meier分析IC53基因自身抗体水平与心力衰竭终点事件的关系。结果：在177例扩张型心肌病中IC53自身抗体阳性率为18.6%，在580例冠心病心衰中为24.1%。平均4年（0.4个月―78个月）的随访中，扩张型心肌病总死亡人数76人，死亡率为42.9%。其中IC53自身抗体阳性病人的死亡数是20人，死亡率为60.6%；自身抗体阴性病人的死亡数是56人，死亡率38.9%。冠心病心衰总死亡人数159人，死亡率为27.1%。其中IC53自身抗体阳性病人的死亡数40人，死亡率为28.6%；自身抗体阴性病人的死亡数119人，死亡率26.6%。我们应用Cox回归分析方法，修正了年龄、性别、以及对终点事件的可能风险因素，分析结果显示扩心病组，IC53抗体阳性病人的死亡率明显高于抗体阴性病人的死亡率，具有明显统计学差异（P=0.010，OR=1.96,95%CI：1.17-3.28）；冠心病组，IC53抗体阳性病人的死亡率与抗体阴性病人的死亡率相似，无统计学差异（P=0.933，HR=1.02,95%CI：0.71-1.46）。应用时间等级检验方法，对扩心病组抗体阳性和阴性病人生存时间制作了Kaplan–Meier曲线，结果显示抗体阳性病人的生存率明显低于抗体阴性病人的生存率。结论：扩张型心肌病心衰病人及冠心病心衰病人血浆中存在IC53基因自身抗体。IC53基因自身抗体增加扩张型心肌病死亡风险，而与冠心病心衰死亡终点无关。IC53基因自身抗体阳性可以作为扩张型心肌病心衰的独立预警信号。急性冠脉综合症急诊介入治疗冠脉内与静脉内注射糖蛋白ⅡbⅢa抑制剂的比较：一个随机对照临床研究的荟萃分析背景：急性冠脉综合征患者行经皮冠状动脉介入治疗（PCI）时，冠脉内（IC）注射IIb/IIIa糖蛋白抑制剂(GPIs)的给药途径是否优于静脉注射(IV)，目前仍然存在争议。方法：我们对比较两种给药途径的随机对照临床研究进行了一个荟萃分析。研究的主要终点是短期(1-3个月)和中长期(6-12个月)主要心血管不良事件(MACEs)(死亡率,再梗死率、靶血管血运重建)。次要终点是术后TIMI血流、TMPG血流分级，术后2周左心室射血分数（LVEF），出血并发症。结果：12项临床研究被纳入荟萃分析。同静脉内使用GPIs相比，冠脉内给药并没有减少短期死亡率(OR:0.71,95%CI:0.41-1.23, P=0.22）和再梗死率（OR:0.76,95%CI:0.45-1.29, P=0.31)。IC组同IV组相比，其短期TVR率呈下降趋势，但没有统计学意义的差异（OR:0.57,95%CI:0.31-1.04, P=0.07）。同静脉内给药相比，冠脉内注射GPIs明显增加了TIMI3级血流（OR:1.48,95%CI:1.06-2.06, P=0.02）和TMPG2-3级血流（OR:2.63,95%CI:1.53-4.51, P=0.0004）。中长期MACEs发生率、LVEF和出血并发症在两组之间无明显差异。结论：急性冠脉综合征患者PCI治疗时，冠脉内直接注射GPIs比静脉注射大大增加靶血管血流量和心肌再灌注，且不增加出血风险，但对临床预后的改善并不优于静脉给药。更多还原

【Abstract】 Association between Autoantibody againstIC53Gene and Prognosis of Patients with Heart FailureBackground: Heart failure (HF) is the final clinical entity of many diverse diseasecauses and mechanisms. During the last years, it has been discovered that autoimmunity playsan important role in the progression and induction of heart failure. Circulating autoantibodies,some of them being heart-specific, have been critically linked to heart failure. The objectiveof study is to determine whether autoantibody against IC53gene is related to prognosis ofpatients with heart failure.Methods: The study included588patients with HF caused by coronary artery disease（CAD） and177patients with HF caused by dilated cardiomyopathy (DCM). Based onsynthetic peptides as antigens, enzyme-linked immunosorbent technique was used firstly todetect the antibody against IC53in serum of the patients. The study population was followedup for a median period of4years until December2013. The end points included cardiac deathand sudden cardiac death (SCD). We performed survival analysis in the HF population. HRs(hazard ratios) for time to cardiac death and SCD from baseline were estimated using Coxproportional hazards models. we analysed Kaplan–Meier curves for time to probability ofsurvival using the log rank test according to positive or negative of antibody against IC53inthe patients with DCM.Results The positve rates of serum for IC53gene were18.6%and24.1%in CHFpatients with DCM and patients with CAD. During a median follow-up period of4years(range,0.4–78months), mortality of patients with DCM was42.9%and mortality ofpatients with CAD was27.1%. Mortality of patients with positive antibody against IC53genein DCM team was60.6%; mortality of patients without positive antibody against IC53gene inDCM team was38.9%. Mortality of patients with positive antibody against IC53gene inCAD team was28.6%; Mortality of patients without positive antibody against IC53gene inCAD team was26.6%. After adjustment for age, gender and suspected risk factors by using asurvival Cox regression analysis, positive antibody against IC53gene in the patients with DCM had an increased risk of cardiac death compared with negative of antibody against IC53in the patients with DCM（P=0.010，HR=1.96,95%CI：1.17-3.28）. Positive antibody againstIC53gene in the patients with CAD had no increased risk of cardiac death compared withnegative of antibody against IC53in the patients with IHD (P=0.933，OR=1.02,95%CI：0.71-1.46).Conclusion: Our results indicated that autoantibody against IC53gene can be detectedin patients with HF. Autoantibody against IC53gene can increase risk of cardiac death in HFcaused by DCM, and serves as an independent predictor of cardiac death. A Comparison of Intracoronary with Intravenous GlycoproteinⅡb/Ⅲa Inhibitors during Percutaneous Coronary Intervention in Patientswith Acute Coronary Syndrome：A Meta-analysis of RandomizedControlled Trials.Background-It is still debatable whether intracoronary(IC) administration ofglycoprotein IIb/IIIa inhibitors (GPIs) is superior to intravenous (IV) administration forpatients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention(PCI).Methods-We performed a meta-analysis of randomized controlled clinical trials. Aliterature search was conducted for relevant trials. Primary end points were short-term (1-3months) and mid-/long term (6/12months) major cardiovascular adverse events(MACEs)(mortality, re-infarction, target vessel revascularization). Secondary end points wereThrombolysis In Myocardial Infarction (TIMI) grade flow, TIMI myocardial perfusion grade(TMPG) flow, left ventricular ejection fraction (LVEF) within2weeks, bleedingcomplication.Results-Twelve studies were included in the meta-analysis. IC administration of GPIsdid not decrease short-term mortality (OR:0.71,95%CI:0.41-1.23, P=0.22) andre-infarction rate (OR:0.76,95%CI:0.45-1.29, P=0.31) compared with IV administration.There was a trend towards reduction of short-term TVR rate in IC group compared with IVgroup but not reached statistical significance (OR:0.57,95%CI:0.31-1.04, P=0.07). ICadministration of GPIs significantly increased TIMI grade3flow (OR:1.48,95%CI:1.06-2.06, P=0.02) and TMPG grade2-3flow (OR:2.63,95%CI:1.53-4.51, P=0.0004)compared with IV administration. No significant difference was observed in long-termMACEs rate, LVEF and bleeding complication between the2groups.Conclusion-IC administration of GPIs in patients with ACS undergoing PCI cansignificantly increase target coronary flow and myocardial reperfusion without increasing the risk of bleeding complication, but can not improve clinical outcome compared with IVadministration.更多还原