【作者】 范莹；

【导师】 夏豪；

【作者基本信息】 武汉大学 ， 心血管内科， 2017， 博士

【摘要】 近年来,冠心病在我国呈现出“井喷”之势。据我国卫生管理的相关部门统计,与20年前相比较,在中国城市,冠心病人口的死亡率增加了73%;中国每年约近100万人死于冠心病,死亡人员总数于2002年已经位居世界第二。冠脉侧枝循环是慢性心肌缺血的代偿机制,对于改善慢性心肌缺血及患者预后具有十分重要的意义。而目前冠脉侧枝循环的形成发展机制并未完全阐明,预测侧枝循环的成熟度和探讨影响冠脉侧枝循环的因素的研究正处于发展阶段。本研究主要从以下三个方面探讨了冠脉侧枝循环的预测因素:(1)C反应蛋白与冠脉侧枝循环的关系;(2)血浆内皮素水平与冠脉侧枝循环的关系;(3)脂蛋白a与冠脉侧枝循环的关系。第一部分C反应蛋白与冠脉侧支循环背景:冠状动脉侧支循环(CCC)作为闭塞性冠状动脉疾病的代偿机制,其影响因素一直受到广泛的关注。本研究以经血管造影确诊的冠状动脉狭窄程度≥95%的患者为研究对象,探讨了 CCC与C反应蛋白水平之间的关系。方法:共1158名患者被纳入研究,所有患者均行冠脉造影检查,其中显示至少一支主要心外膜冠状动脉血管闭塞程度≥95%。根据患者冠脉侧枝循环的形成度分为为两组,CCC形成不良组(Rentrop等级为0-1级)和CCC形成良好组(Rentrop等级为2-3级)。再使用以下两种模式对CRP水平进行分组:第一种模式按照CRP三分位数间距(33%,66%)分三组;第二种模式:分别以1.0mg/L和3.0mg/L作为临界值分三组。进而评估血浆中CRP水平和CCC之间的关系。结果:CCC形成不良组的血清CRP水平差异显著高于形成良好组(5.76±3.45比3.49±2.44mg/L,P<0.001)。与第一位CRP三分位数比较,CCC不足的风险比第二、第三 CRP 三分位数要高(OR2.31,95%CI=1.67～3.19),OR6.25,95%CI=4.52～8.62)。在受试者特征曲线分析中可以得出,预测CCC的最佳CRP临界值是4.21 mg/L,敏感度为59.6%,特异度为74.33%。结论:血清CRP水平是冠脉侧枝循环形成不良的独立预测因子,有望成为临床应用中一个有意义的生物标记物。第二部分血浆内皮素—1与冠状动脉侧支循环背景:冠状动脉侧支循环在修复心脏缺血性损伤中起着十分重要的作用。因此,研究其潜在的影响因素意义重大,尤其对于严重冠状动脉狭窄的患者来说更是具有十分重要的意义。在本研究中,我们以经血管造影确诊的冠状动脉狭窄程度≥95%的患者为研究对象,分析了血浆内皮素-1(ET-1)水平与的冠状动脉侧支循环的关系。方法:纳入研究的1038名患者均接受过冠状动脉造影,患者至少有一支主要的心外膜冠状动脉中狭窄≥95%。将这些研究对象分为两组:冠状动脉侧支循环形成不良组组和冠状动脉侧支循环形成良好组(分别对应Rentrop等级0-2级和3级)。分析和评估血浆ET-1水平与冠状动脉侧支循环的成熟度。结果:血浆ET-1水平在两组之间有的显著差异(分别为0.56±0.44vs.0.33±0.37pmol/l,P<0.001)。血浆 ET-1 值随着 Rentrop 等级的升高而降低,0,1,2,3 级对应的平均值分别为:0.79±0.67pmol/l,0.63±0.48pmol/l,0.42±0.47pmol/l,0.33±0.36pmol/l。此外,血浆ET-1水平升高是不良冠状动脉侧支循环的独立预测因子(OR=3.10,P<0.001)。受试者特性曲线(ROC)分析表明,ET-1水平预测不良冠状动脉侧支循环的最佳临界值为0.30pmol/l,具有60%的敏感性和63.42%的特异性。结论:血浆ET-1很有可能是一个有效的预测严重冠状动脉心脏病患者的冠状动脉侧支循环建立程度的指标。第三部分脂蛋白(a)与冠状动脉侧支循环背景:冠状动脉侧支循环(CCC)作为一种阻塞性冠状动脉疾病的代偿机制,其可能的影响因素长期以来一直受到广泛的关注和探讨。本文对经冠脉造影显示冠状动脉狭窄≥95%的患者进行分析,研究冠状动脉侧支循环与脂蛋白(a)(Lp(a))水平的关系。方法:将654例经血管造影证实至少一支主要冠状动脉狭窄≥95%的患者按照分Rentrop分级(Rentrop分级0、1、2、3级)分为四组。采用以下两种模型分别按照不同的LP(a)水平进行分组:在模式1中,将所有的LP(a)测量值按照三分位法进行分组,其分界值分别为33%和66%;并在模式2中,以LP(a)值为30毫克/分升作为分界值。对冠状动脉侧支循环和血清Lp(a)水平之间的关系进行评估。结果:不同Rentrop分级有显着不同的Lp(a)水平(分别为25.80±24.72、18.99±17.83、15.39±15.80 和 8.40±7.75mg/dl(P<0.001)。在模式 1,第三组 LP(a)水平侧支循环形成不良(Rentrop分级0级)的风险高于第一组LP(a)水平(OR=3.34,95%CI =2.32～4.83)。在模式 2,LP(a)>30mg/dl 组 Rentrop 分级为 0 级的风险超过了 LP(a)<30.0mg/dl 组(OR=6.77,95%CI=4.44～10.4)。结论:Lp(a)水平可以作为不良冠状动脉侧支循环的独立预测因素,同样也可作为临床预测的标志物进行检测。更多还原

【Abstract】 Part one The relationship between C-reactive protein and coronary collateral circulationBackground:Coronary collateral circulation(CCC)is a mechanism that compensates for obstructive coronary artery disease.Exploring CCC’s potential influencing factors has been a long-term interest to cardiologists.In this study,the association between serum C-reactive protein(CRP)levels and CCC was investigated in Chinese patients with angiography-proven 95%coronary stenosis.Methods:There were 1,158 patients enrolled in this study who had undergone coronary angiography and showed 95%occlusion in at least one major epicardial coronary artery.Patients were classified into two groups:poor CCC(Rentrop grades 0-1)and good CCC(Rentrop grades 2-3).CRP levels were grouped using the following two types of models:Mode 1 discretized CRP group with 33 and 66%as the critical values and Mode 2 discretized CRP group with 1.0 and 3.0 mg/L as the cut off values.The association of serum CRP levels with CCC was assessed.Results:There were significant differences in serum CRP levels between the two groups(5.76 ± 3.45 vs.3.49 ± 2.44 mg/L,respectively;p<0.001),and compared with the first CRP tertile,the risks of poor CCC were higher in the second and third CRP tertiles(OR 2.31,95%CI[1.67,3.19],OR 6.25,95%CI[4.52,8.62],respectively).In the receiver operating characteristic curve analysis,the optimal cutoff value of CRP to predict poor CCC was 4.21 mg/L with 59.6%sensitivity and 74.33%specificity.Conclusion:Serum CRP levels is an independent predictor for poor CCC and might supply a useful biomarker in clinical applications.Part two The relationship between endothelin-1(ET-1)and coronary collateral circulationBackground:Coronary collateral circulation(CCC)plays an important role in protecting the heart from ischemic damage.Thus,studies on potential influencing factors are of clinical interest,particularly in patients with severe coronary stenosis.In this study,we investigated the association of plasma endothelin-1(ET-1)levels with CCC in patients with angiography-proven 95%coronary stenosis.Methods:We enrolled 1038 patients who had undergone coronary angiography and had 95%occlusion in at least one major epicardial coronary artery.Patients were classified into the poor or good CCC group(Rentrop grades 0-2 and 3,respectively).The association of plasma ET-1 levels with CCC was assessed.Results:Plasma ET-1 levels differed significantly between the two groups(0.56±0.44pmol/L vs.0.33±0.37pmol/L,p<0.001).ET-1 values decreased with increasing Rentrop grade(0,1,2,and 3),with mean ET-1 values of 0.79±0.67pmol/L,0.63±0.48pmol/L,0.42±0.47pmol/L,and 0.33±0.36pmol/L,respectively.Moreover,higher plasma ET-1 levels were an independent predictor for poor CCC(odds ratio 3.10,p<0.001).The receiver operator characteristic curve analysis indicated that the optimal ET-1 cut-off value to predict poor CCC was 0.30pmol/L with 60%sensitivity and 63.42%specificity.Conclusions:Our data firstly indicated that plasma ET-1 might be a useful,easily available predictor for CCC degree in patients with severe coronary artery disease.Part three The relationship between Lipoprotein(a)(Lp(a))and coronary collateral circulationBackground:As a mechanism compensating for obstructive coronary artery ailment,coronary collateral circulation(CCC)has attracted extensive cardiologists for a long time to explore its possible impact factors.In the paper,Chinese patients were suffered from 95%coronary stenosis,as diagnosed by angiography,to study the relationship between CCC and Lipoprotein(a)(Lp(a))levels.Methods:A total of 654 subjects were suffered from 95%occlusion of at least one major coronary occlusion,as diagnosed by angiography,which were divided into four categories:Rentrop grade 0,1,2,3.The models below had been applied to divide Lp(a)levels:in Mode 1,Lp(a)group was discretized,whose critical value was 33 and 66%;and in Mode 2,it was discretized and its cut off value was 30.0 mg/dl.Furthermore,we evaluated the relationship between CCC and serum Lp(a)levels.Results:The four groups had significantly different Lp(a)levels(25.80±24.72,18.99±17.83,15.39±15.80,and 8.40±17.75mg/dl respectively;p<0.001).In mode 1,concerning R0,its risk in the third Lp(a)tertile(OR 3.34,95%CI[2.32,4.83])was greater than that in the first Lp(a)tertile.In mode 2,concerning R0,its risk in Lp(a)>30.0 group(OR 6.77,95%CI[4.44,10.4])was greater than of Lp(a)<30.0mg/dl.Conclusions:The worse condition of CCC can be predicted independently by Lp(a)levels.In clinical,besides,Lp(a)levels can also be used biologically for marking.更多还原