和肽素测定对急性心肌梗死早期诊断 病情评估及预后的研究 田卫东 吉林大学 分类号 :R541.4 单位代码 :10183 研究生学号 :2013744022 密级 : 公开 吉林大学 硕士学位论文 ( 专业学位 ) 和肽素测定对急性心肌梗死早期诊断 病情评估及预后的研究 The study of copeptin in early diagnosis, evaluation and prognosis of acute myocardial infarction 作者姓名 : 田卫东 类 别 : 临床医学硕士 领域 ( 方向 ): 内科学 指导教师 : 张静教授 培养单位 : 第二医院 2016 年 4 月
和肽素测定对急性心肌梗死早期诊断 病情评估及预后的研究 The study of copeptin in early diagnosis, evaluation and prognosis of acute myocardial infarction 作者姓名 : 田卫东 领域 ( 方向 ): 内科学 指导教师 : 张静教授 类 别 : 临床医学硕士 答辩日期 : 年月日
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中文摘要和肽素测定对急性心肌梗死早期诊断 病情评估及预后的研究研究背景 : 冠心病 (Coronary Heart Disease,CHD) 是严重威胁人们健康的常见和多发疾病, 近年来, 其发病率和死亡率呈逐年上升的趋势 急性心肌梗死 (Acute Myocardial Infarction,AMI) 是冠心病的严重类型之一, 死亡率较高, 在临床上约有 25% 的心肌梗死患者在发病早期缺乏典型的临床症状, 对此类患者进行早期诊断和病情评估具有十分重要的意义 精氨酸加压素 (Arginine vasopressin, AVP) 是反映下丘脑 - 垂体 - 肾上腺轴激活水平的敏感指标, 具有收缩血管 升高血压 抗利尿等循环调节效应, 还参与机体的应激反应, 是心血管疾病发生发展过程中神经内分泌介质中的一种, 也是反映危重病严重程度及预后的重要标记物 和肽素 (copeptin) 是精氨酸加压素原 C 末端的一部分, 在体内比较稳定, 便于测定 在正常人群和多种心血管疾病患者的血液中和肽素水平与 AVP 呈显著正相关, 和肽素有望成为多种疾病的临床预警生物标志物 目的 : 探讨人血清和肽素水平与急性心肌梗死早期诊断 病情评估及近期预后的关系 方法 : 选取 2015 年 10 月 2015 年 12 月在吉林大学第二医院心内科就诊并经冠状动脉造影或相关生化指标检测明确诊断为急性心肌梗死的患者 72 例, 男性 53 例, 女性 19 例, 年龄 34-85 岁, 平均 (62.03±11.27) I
岁 (AMI 组 ), 不稳定型心绞痛患者 26 例, 男性 16 例, 女性 10 例, 年龄 40-76 岁, 平均 (60.12±8.62) 岁 (UA 组 ) 同期就诊于我院行冠状动脉 CT 或冠状动脉造影检查提示冠状动脉狭窄程度 <50% 的患者设为对照组, 为 25 例, 男性 14 例 女性 11 例, 年龄 40-79 岁, 平均 (58.36 ±11.93) 岁 AMI 的诊断采用 2007 年心肌梗死全球统一定义中推荐的急性心肌梗死的诊断标准 所有入组患者均除外尿崩症 急性心力衰竭 严重感染 急性脑梗塞 肺动脉高压 慢性肺源性心脏病 严重肝肾功能不全 恶性肿瘤等 除外 3 例未行冠脉造影的患者, 将 69 例行冠脉造影检查的 AMI 患者根据冠状动脉造影结果分为单支血管病变组 (20 例 ) 2 支血管病变组 (21 例 ) 3 支血管病变组 (28 例 ); 参照 Gensini 评分系统对每位 AMI 患者的冠状动脉狭窄程度进行定量评定, 分为 40 分组 (18 例 ) 和 >40 分组 (51 例 ) 对 72 例急性心肌梗死患者进行为期 1 个月的随访, 根据患者是否发生主要心脏不良事件, 分为有 MACE 组和无 MACE 组 ( 心梗后心绞痛组 26 例 无心梗后心绞痛组 46 例 ; 心梗后心衰组 24 例 无心梗后心衰组 48 例 ; 死亡组 7 例 存活组 65 例 ) 收集患者入院当天血压 血脂 心肌损伤标志物 和肽素 NT-proBNP CK-MB hs-crp 等指标, 同时观察急性心肌梗死发病后 1 个月内的 MACE 发生情况 结果 :1)AMI 组 UA 组 对照组患者在年龄 性别 收缩压 舒张压 甘油三酯 (TG) 肌酐 糖尿病病史 高血压病史等方面差异无统计学意义 (P>0.05) AMI 组 UA 组患者 TC LDL-C 水平明显高于对照组,HDL-C 水平低于对照组, 差异有统计学意义 (P< II
0.05), 而 AMI 组与 UA 组之间 TC LDL-C 和 HDL-C 水平无明显差异 (P>0.05) ctni 肌红蛋白 NT-proBNP CK-MB hs-cr 水平在 AMI 组患者中明显高于 UA 组和对照组 (P<0.05), 后两者间比较无统计学差异 (P>0.05) AMI 组血清和肽素水平 [(16.17± 4.24)pmol/L] 明显高于 UA 组 [(11.57±2.77) pmol/l] 和对照组 [(9.60±2.73) pmol/l],ua 组明显高于对照组, 差异均有统计学意义 (P<0.05) 2) 胸痛发作在 3 小时内的 AMI 患者的血清 copeptin ctni 肌红蛋白水平均明显高于对照组(P<0.05), 而 3h 内 CK-MB 水平与对照组比较差异无显著性 (P>0.05) 3)3 支血管病变组和 2 支血管病变组患者的血清和肽素水平均明显高于单支病变组和对照组, 差异有统计学意义 (P<0.05), 而 3 支血管病变组和 2 支血管病变组比较和肽素水平无明显差异 (P>0.05) 各组间 ctni CK-MB 相比较差异均无显著性 (P>0.05) 4)Gensini 积分 >40 分组患者的血清和肽素水平明显高于积分 40 分组患者, 差异有统计学意义 (P <0.05), 两组间 hs-crp ctni CK-MB NT-proBNP 水平相比较, 差异均无显著性 Pearson 相关性分析显示 AMI 患者和肽素水平与 Gensini 积分呈正相关 (r=0.401,p<0.01) 5) 出现心梗后心力衰竭患者的血清和肽素 NT-proBNP 水平明显高于无心梗后心力衰竭患者, 差异有统计学意义 (P<0.05) 6) 死亡组患者血清和肽素 Gensini 积分均明显高于存活组患者, 差异有统计学意义 (P<0.05), 而两组间 ctni NT-proBNP CK-MB 水平无显著性差异 (P>0.05) 结论 :1) 和肽素在急性心肌梗死的早期即明显升高, 联合检测和肽素 III
和肌钙蛋白有利于急性心肌梗死的早期诊断 ;2) 血清和肽素在一定程度上可反映冠状动脉的病变程度, 且优于 hs-crp ctni CK-MB NT-proBNP 的评估价值 ;3) 和肽素对 AMI 后近期 MACE 的发生有一定的预测价值 关键词 : 急性心肌梗死, 和肽素, 肌钙蛋白 I,NT-proBNP, 高敏 C 反应蛋白, 肌酸激酶同工酶, 主要心脏不良事件 IV
Abstract The study of copeptin in early diagnosis, evaluation and prognosis of acute myocardial infarction Background:Coronary Heart Disease (Coronary heart disease, CHD) is a common and frequently encountered disease that threatens human health seriously and its incidence and mortality is still increasing year by year. Acute myocardial infarction is a severe form of coronary heart disease. In clinical, we found that about 25 percent of patients with myocardial infarction did't have typical clinical symptoms in the early stages, therefore to diagnose early and assess severity of these patients is important. Arginine vasopressin (AVP) is a sensitive indicator of the hypothalamic - pituitary - adrenal axis activation level.it has a circulating regulatory effect on contracting blood vessels, increasing blood pressure, antidiuretic and all that. It is also involved in the body's stress response. It is not only one of the neuroendocrine medium in the occurrence and development of cardiovascular disease, but also a significant marker that can reflect the severity and prognosis of critical illness. Copeptin is a part of the C-terminal of pre-provasopressin, which is relatively stable in the body and easy to determine. In the normal population and patients with a variety of cardiovascular diseases,there is significant correlation between copeptin and AVP. Copeptin is expected to be an early warning sign of V
many diseases.it has been found in recent studies that copeptin may have great value in the diagnosis and prognosis of cardiovascular disease. Objective: To discuss the relationship between human serum copeptin level and the early diagnosis,condition assessment and short-term prognosis of acute myocardial infarction. Methods:We selected 72 patients who visited Department of Cardiology, the Second Hospital of Ji lin University from october 2015 to december 2015 and were diagnosed as acute myocardial infarction by coronary angiography(cag) or related laboratory tests as AMI group, of which there are 53 males and 19 females aged 34 to 85 with an average age of 62.03 ± 11.27.Meanwhile,26 patients with unstable angina, aged 40 to 76,were selected in UA group and there are 16 males and 10 females, with a mean age of 60.12 ± 8.62. In the control group, there are 25 patients(14 males and 11 females, aged 40-79 years old, mean age 58.36 ± 11.93) who visited our hospital over the same period and underwent coronary CT or CAG prompting coronary artery stenosis <50%. The patients with AMI is diagnosed by the diagnostic criteria for myocardial infarction in 2007, recommended by the global uniform definition in acute myocardial infarction. All enrolled patients with insipidus, acute heart failure,severe infection, acute cerebral infarction, pulmonary hypertension, chronic pulmonary heart disease, severe liver and kidney dysfunction, cancer and so on were excluded. Except for 3 patients who VI
did not undergo coronary angiography,the 69 patients with AMI, according to the results of coronary angiography,were divided into single-vessel disease group (20 cases), 2 branch lesions group (21 cases), 3 branch lesions group (28 cases) ; on the basis of Gensini scoring system,the patients with AMI were divided into 40 group(18 cases) and> 40 group(51 cases). The 72 patients with AMI were followed up for one month and according to the presence or absence of major adverse cardiac events,they are divided into group with MACE and non- MACE group (Angina after myocardial infarction was 26 cases, no post-mi angina group was 46 patients; 24 cases of heart failure after myocardial infarction, 48 cases of myocardial infarction without heart failure; deaths group 7 cases, survival group 65 cases).patients' clinical data were collected, including blood pressure, blood lipid, myoglobin, troponin I, copeptin, NT-proBNP, high-sensitivity C-reactive protein (hs-crp), creatine kinase (CK-MB), major adverse cardiac events (MACE) within one month after AMI. Results: 1) There was no significant statistical difference between AMI group, UA group and the control group in age, sex, systolic blood pressure, diastolic blood pressure, triglyceride (TG), creatinine, history of diabetes and hypertension, etc(p> 0.05). The TC, LDL-C level in AMI group and UA group was significantly higher,and HDL-C level was lower than control group, which has statistically significance(p <0.05), and the VII
difference of TC, LDL-C and HDL-C between AMI group and UA group was not statistically significant (P> 0.05). The ctni, myoglobin, NT-proBNP, CK-MB and hs-crp levels in AMI patients were obviously higher than UA group and control group (P <0.05), and differences were no significant between the two latter(p > 0.05 ). The serum copeptin level in AMI group[(16.17±4.24)pmol/l] was distinctly higher than the UA group[(11.57±2.77) pmol/l] and control group [(9.60±2.73) pmol/l] and the UA group was also significantly higher than control group,of which both had statistically significant difference (P <0.05).2) During 3 hours after chest pain occurs, the serum copeptin, myoglobin and ctni level of AMI patients was significantly higher than control group (P <0.05),but CK-MB level had no significant difference compared with control group (P> 0.05). 3) Serum copeptin level in 2 branch lesions group and 3 branch lesions group was significantly higher than single-vessel disease group and control group (P <0.05),while 3 branch lesions group had no statistically significant difference with 2 branch lesions group (P> 0.05).The ctni, CK-MB level of each group had no significant difference (P> 0.05).4) Serum copeptin level in group with Gensini score> 40 was significantly higher than group with Gensini score 40 and the difference had statistically significance (P <0.05). Pearson correlation analysis showed that copeptin level was positively correlated with Gensini score (P <0.05). The hs-crp, ctni, CK-MB and NT-proBNP level between the VIII
two groups was not statistically significant. 5) Copeptin and NT-proBNP level in patients with heart failure after myocardial infarction was significantly higher than that without heart failure (P <0.05). 6) Serum copeptin level and Gensini score of death group were both significantly higher than survival group (P <0.05),while the ctni,ck-mb and NTproBNP between the two groups had no significant difference ( P> 0.05). Conclusion: 1) Copeptin is obviously higher in the early acute myocardial infarction and combined detection of copeptin and cardiac troponin is conducive to the early diagnosis of acute myocardial infarction. 2) To some extent, serum copeptin may reflect coronary artery disease degree, and better than hs-crp, ctni, CK-MB and NT-proBNP. 3) Copeptin has some predictive value on recent MACE after AMI. Keywords: acute myocardial infarction,copeptin,cardiac troponin I,N-terminal B-type natriuretic peptide,high-sensitivity C-reactive protein,creatine kinase,major adverse cardiac events IX
目录第 1 章引言... 1 第 2 章综述... 3 2.1 和肽素的特点... 3 2.2 和肽素与精氨酸加压素的关系... 4 2.3 和肽素与冠心病的关系... 4 2.4 和肽素与心力衰竭的关系... 6 第 3 章资料与方法... 8 3.1 一般资料... 8 3.2 研究方法... 10 3.3 统计学处理... 11 第 4 章结果... 12 4.1 AMI 组 UA 组 对照组患者一般资料比较... 12 4.2 AMI 患者 copeptin ctni CK-MB 肌红蛋白水平随时间变化... 13 4.3 血清 copeptin ctni CK-MB NT-proBNP hs-crp 水平与 AMI 患者冠状动脉狭窄程度的关系... 15 4.4 血清 copeptin ctni CK-MB NT-proBNP 水平及 Gensini 积分与 AMI 患者发病 1 个月内主要心脏不良事件的关系... 17 第 5 章讨论... 21 5.1 和肽素与急性心肌梗死的早期诊断... 22 5.2 和肽素与急性心肌梗死患者冠状动脉狭窄程度的关系... 23 X
5.3 和肽素与急性心肌梗死的预后... 25 第 6 章结论... 27 参考文献... 28 作者简介及发表的论文... 34 致谢... 35 XI
缩略词对照表 英文缩写 英文名称 中文名称 CHD Coronary heart disease 冠心病 UA Unstable angina 不稳定型心绞痛 AMI Acute myocardial infarction 急性心肌梗死 HF Heart failure 心力衰竭 SBP Systolic blood pressure 收缩压 DBP Diastolic blood pressure 舒张压 TG Triglycerides 甘油三酯 TC Total cholesterol 总胆固醇 HDL-C High-density lipoprotein 高密度脂蛋白胆固醇 cholesterol LDL-C Low-density lipoprotein 低密度脂蛋白胆固醇 cholesterol hs-crp High-sensitivity 高敏 C 反应蛋白 C-reactive protein CK-MB Isoenzymes of creatine 肌酸激酶同工酶 kinase Myo Myoglobin 肌红蛋白 ctni Cardiac troponin I 肌钙蛋白 I NT-proBNP N-terminal B-type N 末端 B 型脑钠肽 natriuretic peptide XII