【作者】 叶忠；

【导师】 郑兴； 秦永文； 徐荣良；

【作者基本信息】 第二军医大学 ， 内科学， 2009， 硕士

【摘要】 背景:冠心病(coronary heart disease,CHD)是严重危害人类生命健康和影响人类生活质量的常见病,其发病率和死亡率呈逐年上升趋势。近年来,生物标记物作为预测冠心病的有用工具正在逐渐受到人们的重视。最近,一项大规模临床研究显示,和肽素(copeptin)是冠心病心肌梗塞后患者死亡率的独立预测因子,特别是在N末端脑钠素原(N-terminal pro-B-type natriuretic peptide,NTproBNP)升高的患者中预测价值更高。和肽素是精氨酸加压素原(pre-provasopressin)的C末端的一部分,和精氨酸加压素(arginine vasopressin,AVP)一起由神经垂体等量分泌,AVP检测困难,而和肽素检测方便,快捷,有研究表明,和肽素可能成为临床上常规测量循环中AVP水平的替代物。AVP在下丘脑-垂体-肾上腺轴的调节中起着重要作用,反映了机体的应激反应能力。由于是否存在心肌缺血以及心肌缺血的程度有力地预测了冠心病的死亡率,所以我们假定和肽素和AVP系统可能与心肌缺血相关联。PASSAT研究也支持这个假设,他们研究发现AVP水平在急性心肌梗塞患者行经皮冠状动脉介入治疗术(percutaneous coronary intervention,PCI)后立即升高,提示冠心病心肌缺血可能引起AVP分泌。目前有研究发现,AVP系统可能是除肾素—血管紧张素系统和交感神经系统以外的另一个与急性心梗后预后不良相关联的神经激素路径。但和肽素与冠心病的关系仍未明确,尤其是与冠心病冠脉病变严重程度的关系尚不清楚。目的:探讨人血浆copeptin水平与冠心病、冠脉病变严重程度及冠心病危险因素的关系。方法:选取2008-10～2009-1因可疑冠心病在长海医院心内科住院而进行冠状动脉造影检查的180例患者,以冠脉病变支数和Gensini积分评价冠脉病变严重程度。按冠脉造影结果分为冠心病组(101例)与对照组(79例)。冠心病组再分别根据冠脉病变支数、Gensini积分分为若干个亚组,即根据冠脉病变支数分为单支病变、双支病变、三支病变;根据Gensini积分分为0<积分<20、20≤积分<40和积分≥40三组。所有患者造影前均以copeptinEIA药盒测定血浆copeptin水平、用自动生化分析仪测定总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、空腹血糖(FPG);同时测量收缩压(SBP)、舒张压(DBP)、体重指数(BMI)等相关指标,询问吸烟史、高血压病史及糖尿病史。运用统计学方法比较各组患者临床和生化指标的不同,并计算血浆copeptin水平与冠心病传统危险因素的相关系数。连续变量符合正态分布的用平均值±标准差( x±s )表示,不符合正态分布的资料(BMI)用中位数及四分位数表示。正态分布资料两组间均数的比较采用成组t检验,多组间均数比较采用方差分析并进一步进行了各组间均数的两两比较。不符合正态分布的资料两组间比较(BMI)采用的是成组资料的非参数检验,多组间比较采用的是完全随机设计资料的非参数检验。计数资料间的比较用χ2检验。正态分布资料的相关分析采用Pearson直线相关,非正态分布资料的相关分析采用spearman秩相关。本研究数据均采用SAS9.1.3软件进行统计分析。P<0.05认为有统计学意义。结果:①冠心病患者血浆copeptin水平显著高于正常对照组(0.9536±0.0986ng/ml vs 0.9244±0.0649ng/ml,P<0.05)。②冠状动脉多支病变组(即双支病变组和三支病变组)的血浆copeptin水平显著高于对照组和单支病变组(P<0.05),双支病变组和三支病变组的血浆copeptin水平无显著差异(P>0.05),Gensini积分≥20组(即20≤积分<40组和积分≥40组)的血浆copeptin水平显著高于对照组和0<积分<20组(P<0.05);20≤积分<40组和积分≥40组的血浆copeptin水平无显著差异(P>0.05)。③血浆copeptin水平与年龄、BMI、血压、吸烟、高血压病、糖尿病、TC、TG、LDL-C、HDL-C、FPG等无相关。结论:冠心病患者血浆copeptin水平显著升高,在双支病变组、三支病变组、20≤积分<40组和积分≥40组尤为显著,提示血浆copeptin水平可以作为反映冠脉病变严重程度的参考指标;血浆copeptin水平与年龄、BMI、血压、吸烟、高血压病、糖尿病、TC、TG、LDL-C、HDL-C、FPG等冠心病传统危险因素无相关。更多还原

【Abstract】 Background:Coronary heart disease (CHD) is a common disease and a principal cause of death in adults, it’s morbility and mortality rates are increasing year by year. Biomarkers have emerged as a useful tool for predicting prognosis in patients with coronary heart disease. Very recently, a large clinical research found that copeptin has been shown to be an independent predictor of death in patients with AMI, especially in those with an elevated NTproBNP. Copeptin, the C-terminal part of the vasopressin prohormone, is secreted stoichiometrically with vasopressin from the neurohypophysis. However, AVP is unstable in isolated plasma and AVP measurement is cumbersome. While copeptin is very stable in vitro, and can be quickly and easily measured. There are some researches found that the copeptin assay may be a useful alternative to direct measurement of AVP concentration. AVP plays a crucial role in the regulation of the hypothalamo-pituitary–adrenal axis, reflecting the individual stress response. As the presence and the extent of myocardial ischemia strongly predicts mortality in CHD ,we hypothesized that copeptin and the AVP system may be involved in the response to myocardial ischemia. Also the results from the PASSAT study supported this hypothesis. They found, that levels of AVP increased immediately after percutaneous coronary intervention in patients with acute myocardial infarction,suggesting also that myocardial ischemia may induce AVP secretion. The present findings suggest that the AVP system is another candidate neurohormonal pathway, in addition to the renin-angiotensin and sympathetic nervous systems, that may be associated with poor outcome after AMI. However, the role of copeptin in coronary heart disease remains to be established, especially the association of copeptin with the severity of coronary atherosclerosis.Objective : To see whether plasma copeptin correlates with coronary heart disease(CHD),severity of coronary atherosclerosis and other established cardiovascular risk factors.Methods:Coronary angiography (CAG) was performed in 180 hospitalized patients who were suspected as having coronary heart disease (CHD). The severity of pathological changes of the coronary artery was assessed by the number of diseased coronary branches and Gensini’s score. According to the results of CAG, the 180 patients were divided into two groups: CHD group (n=101) and non-CHD group as control (n=79). The CHD patients were further divided into subgroups according to the number of diseased coronary branches and Gensini’s score. Plasma copeptin, lipids, fasting plasma glucose ,blood pressure, body mass index were measured, and age, sex and prior medical histories including hypertension, diabetes mellitus and smoking status were obtained before CAG in all patients. Copeptin were compared statistically between the subgroups, and correlation coefficient of copeptin and other conventional risk factors for CHD was calculated. Measurement data which follows the normal distribution were described with mean±std and T-test was used to compare the difference between two groups and the difference among three or more groups were compared with ANOVA. In addition, the Pearson method was also employed for the correlation analysis. The data which do not follows the normal distribution(BMI) were described with median and quartile and compared with Wilcoxon rank sum test and Kruskal-Wallis H test. The difference between enumeration data were compared with Chi-square test and the Spearman method was used for the correlation analysis. All the data were analyzed by SAS9.1.3 and P<0.05 was supposed to be statistically significant.Results:1) Plasma copeptin in CHD patients was significantly higher than that in controls (0.9536±0.0986ng/ml vs 0.9244±0.0649ng/ml,P<0.05); 2) Plasma copeptin in double diseased coronary branches subgroup and three diseased coronary branches subgroup was respective significantly higher than that in controls and single diseased coronary branche subgroup(P<0.05), but plasma copeptin in double diseased coronary branches subgroup and three diseased coronary branches subgroup have no significant statistical difference(P>0.05).Plasma copeptin in 20≤Gensini’s score<40 subgroup and Gensini’s score≥40 subgroup was respective significantly higher than that in controls and 0<Gensini’s score<20 subgroup(P<0.05), but plasma copeptin in 20≤Gensini’s score<40 subgroup and Gensini’s score≥40 subgroup have no significant statistical difference(P>0.05);3) Plasma copeptin was not correlated with age, body mass index, blood pressure,smoking status, hypertension, diabetes mellitus,TC ,TG, LDL-C;HDL-C, and FPG.Conclusion: 1) Plasma copeptin level is significantly increased in patients with coronary heart disease, especially in double diseased coronary branches subgroup, three diseased coronary branches subgroup, 20≤Gensini’s score<40 subgroup and Gensini’s score≥40 subgroup, which indicate that plasma copeptin level can be used as a parameter to predict pathological severity of coronary atherosclerosis. 2) Plasma copeptin is not correlated with age, body mass index, blood pressure,smoking status, hypertension, diabetes mellitus,TC ,TG, LDL-C;HDL-C, and FPG.更多还原