【作者】 吕先光；

【导师】 刘朝中；

【作者基本信息】 第四军医大学 ， 内科学， 2008， 硕士

【摘要】 背景和目的力衰竭的病理生理机制主要包括血流力学的异常、心肌损害和心室重构、神经内分泌的激活。此三者互为因果,相互关联形成恶性循环加重心功能的恶化。心力衰竭的病理生理机制十分复杂,我们通过研究发现除了上述三种主要机制外,体内存在的多种活性物质可能与心力衰竭发生、发展密切相关。本课题通过与对照组的对比研究,观察血浆B型钠酸肽、C-反应蛋白、D-二聚体、纤维蛋白原和内皮素-1浓度在正常体检组、心脏病心功能正常组和慢性心力衰竭组中的变化,探讨慢性心衰患者心功能严重程度和近期心血管事件的发生与外周血B型钠酸肽、C-反应蛋白、D-二聚体、纤维蛋白原和内皮素-1浓度的变化与纽约心脏病协会心功能分级及超声心动图所测指标的关系和临床意义。方法按照Framingham关于慢性心力衰竭的诊断标准,入选2006年9月至2007年9月在我院住院的慢性心力衰竭患者75例,其中,男31例,年龄68.26±13.39岁;女44例,年龄70.75±9.89岁。根据临床症状、病史、心电图、X线胸片、彩色多普勒超声心动图及实验室检查确诊为心力衰竭的患者按纽约心脏病协会心功能分级标准进行分组,分为I级+II级组22例(男8例,女14例)、Ⅲ级组24例(男9例,女15例)、IV级组29例(男13例,女16例)。另外选取体检正常者20例(男11例,年龄55.00±16.06岁;女9例,年龄46.33±16.50岁)、有器质性心脏病但心功能正常的21例(男10例,年龄64.20±7.01岁;女11例,年龄69.91士10.19岁)为对照组,采用美国BIOSITE公司的Trige分析仪检测外周血B型钠酸肽的浓度、免疫浊度法测定C-反应蛋白浓度和D-二聚体的浓度、酶联免疫吸附法测定纤维蛋白原浓度、放射免疫法测定内皮素-1的浓度,研究正常对照组、心脏病心功能正常组、慢性心功能不全组这三组间B型钠酸肽、C-反应蛋白、D-二聚体、纤维蛋白原和内皮素-1浓度的浓度变化与纽约心脏病协会心功能分级和超声心动图所测指标的相关性,同时对慢性心衰患者随访半年,观察心血管病事件的发生情况。结果(1) B型钠酸肽值分别为:正常对照组18.59±12.09 pg/ml,心脏病心功能正常组80.88±59.99 pg/ml,I+II级组316.20±134.58pg/ml,III级组680.47±397.3pg/ml,IV级组1203.46±528.66pg/ml,慢性心衰组B型钠酸肽水平显著高于对照组,各不同纽约心脏病协会心功能分级组间B型钠酸肽水平有显著差异(P<0.05),B型钠酸肽水平与心功能分级呈正相关(Spearman相关系数r=0.843, P<0.05),与左室射血分数呈负相关(Spearman相关系数r=0.845,P <0.05)(2)与正常对照组、心脏病心功能正常组相比较,慢性心力衰竭组C-反应蛋白、D-二聚体、纤维蛋白原、内皮素-1浓度升高,各组间两两比较也有显著性差异(P<0.05)。随着纽约心脏病协会心功能分级的升高,C-反应蛋白、D-二聚体、纤维蛋白原、内皮素-1浓度也升高,其Spearman相关系数分别为r=0.832,0.756,0.620。(3)与正常对照组相比较,慢性心力衰竭组左心房内径、左心室舒张末内径均增大,左心室射血分数和左室短轴缩短率均减小,随着纽约心脏病协会心功能分级的升高,左心房内径和左心室舒张末内径均增加,左心室射血分数和左室短轴缩短率均降低,差异有统计学意义(P <0.05)。(4)以C-反应蛋白、D-二聚体、内皮素-1、纤维蛋白原、年龄、心率、红细胞计数、白细胞计数、血红蛋白含量、血糖、血尿素氮、血肌酐、血尿酸、总胆固醇、甘油三酯、高密度脂蛋白、低密度脂蛋白、体重指数为自变量,B型钠酸肽为因变量,运用Stepwise逐步回归分析的方法,最终只有C-反应蛋白、D-二聚体、纤维蛋白原进入回归方程,t值分别为5.780、5.369、4.519,P<0.05。(5)用受试者工作特征曲线分析显示:曲线下面积为0.741,其95%的可信区间为(0.647,0.835),P<0.05。当B型钠酸肽取截断点83.75pg/ml时,B型钠酸肽预测心血管事件的敏感性为86.1%,特异性为36.2%。结论(1)慢性心力衰竭患者外周B型钠酸肽浓度与心力衰竭严重程度密切相关,纽约心脏病协会心功能分级越高,B型钠酸肽的水平也越高。B型钠酸肽水平可以反映心功能状态辅助诊断慢性心力衰竭并可作为疗效和预后评估的观察指标。(2)慢性心力衰竭患者存在非特异炎症反应,C-反应蛋白浓度升高,且与心功能状况密切相关。(3)慢性心力衰竭患者存在凝血系统的紊乱,D-二聚体、纤维蛋白原水平升高且与心衰严重程度密切相关。(4)慢性心力衰竭患者存在内皮功能紊乱,内皮素-1浓度升高且与纽约心脏病协会心功能分级心功能分级密切相关。(5)B型钠酸肽、C-反应蛋白、D-二聚体、纤维蛋白原和内皮素-1相互作用,共同参与慢性心力衰竭的病理生理过程。更多还原

【Abstract】 Groundback and Objective The pathophysiology mechanisms in chronic heart failure mainly include haemodynamic abnormality, myocardial damage and left ventricular remodeling, neuroendocrine activation. The three reciprocal causation form vicious cycle and worsen heart function. Up to now, the pathophysiology mechanism of chronic heart failure is still complex and not fully defined. We found that, in addition to the three main mechanisms, maybe there exist intimate correlation to kinds of active material in human body with heart failure. According to compared with control group, we observed the change of plasma levels of B-type natriuretic peptide, C-reactive protein, D-dimer, endothelial-1, fibrinogen in patients with chronic heart failure and analyzed correlation between New York heart association class and the parameter measured by echocardiography.Methods 116 patients were enrolled in the study including 20 cases(males 11, 55.00±16.06 years; females 9,46.33±16.50 years) without any disease as control group(named Group 1), 21 cases (males 10,64.20±7.01 years;females 11, 69.91±10.19 years)with heart disease but non-dysfunction as heart disease group(named Group 2), 75 cases (males 31,68.26±13.39 years;females 44,70.75±9.89 years)with heart disease and dysfunction as chronic heart failure group(named Group 3,4,5 respectively). We measured B-type natriuretic peptide with Triage Analyzer produced by BIOSITE Co.ltd Americia, C-reactive protein with immunoturbidimetry assay, endothelin-1 with radioimmunoassay, D-dimer and fibrinogen with enzyme-linked immunoassay. This study is to do a comparison of B-type natriuretic peptide, C-reactive protein, D-dimer, endothelial-1 and fibrinogen concentration inter-groups containing Group 1 (n=20), Group 2(n=21) and Group 3, 4, 5(n=75) and echocardiograms were detected in all patients. Correlation between B-type natriuretic peptide, C-reactive protein, D-dimer, endothelial-1, fibrinogen concentration was also analyzed in every group. To observe cardiaovascular events incidence rate, chronic heart failure group was followed for six months.Results(1) Plasma B-type natriuretic peptide concentrations in Group1, Grup2, Group3, Group4, Group5 was 18.59±12.09 pg/ml , 80.88±59.99 pg/ml ,316.20±134.58pg/ml,680.47±397.3pg/ml,1203.46±528.66pg/ml respectively and increased in Group3, Group4, Group5 compared with Group1 and Grup2 significantly(P<0.05). B-type natriuretic peptide concentration had significantly differences between Group3, Group4, Group5 and was positively correlation with NYHA class(r=0.843, P<0.05) , negatively correlation with left ventricle ejection fraction (r= - 0.845,P<0.05) in whole 5 group.(2) Compared with group1 and group2, C-reactive protein, D-dimer, endothelial-1, fibrinogen concentrations increased and existed significantly difference between Group3, Group4 and Group5. The plasma level of C-reactive protein, D-dimer, endothelial-1, fibrinogen increased according to NYHA cardiac class and were significance correlated with New York heart association class. The spearman coefficient of correlation of C-reactive protein, D-dimer, endothelial-1, fibrinogen is 0.787, 0.770, 0.597, 0.644 respectively(P<0.05).(3) Left atrial diameter and left ventricle end-diastolic diameter increased in Group 3,4,5 compared with Group1 and Grup2(P<0.05)while left ventricle ejection fraction and fraction shortening were lower than in Group1 and Grup2 (P<0.05). The scale of left atrial diameter and left ventricle end-diastolic diameter is gradually increasing as New York heart association class upgraded while left ventricle ejection fraction and fraction shortening is gradually decreasing.(4) Stepwise multivariate regression analysis was used with 18 variables, included C-reactive protein, D-dimer, endothelin-1,fibrinogen,year, heart rate, red blood cell count, white blood cell count, haemoglobin, blood glucose, blood uric acid, total cholesterol, triglyceride, high density lipoprotein,low density lipoprotein, body mass index as independent variable and the B-type natriuretic peptide as dependent variable. We founded that only C-reactive protein, D-dimer and fibrinogen entered the regression equation (t=5.780, 5.369, 4.519, P<0.05, respectively).(5) By Receiver operating characteristic curve we founded that the area under the cure was 0.741, CI(0.647,0.835), and the sensitivity was 86.1%, speciality was 36.2% when the B-type natriuretic peptide cutoff was 83.75 predicting cardiovascular events. Conclusion(1) The level of B-type natriuretic peptide is increasing in patients with chronic heart failure and obviously related with New York heart association class. The more upgraded New York heart association class ,the more high the level of B-type natriuretic peptide. The level of B-type natriuretic peptide can reflex cardiac status diagnosing chronic heart failure and serve as an index to evaluate curative effect and prognosis on patients with chronic heart failure.(2) There is the non-special inflammatory lesion in patients with chronic heart failure. Increased level of the C-reactive protein suggests there is a non-special inflammatory lesion, which correlate with bad cardiac function closely.(3) Patients with chronic heart failure show evidence of hypercoagulability and fibrinolysis activation. The level of D-dimer and fibrinogen increased in patients with chronic heart failure are related with severe degree of heart failure intimately.(4) Chronic heart failure has an important impact on abnormality of endothelial cell function. The concentratin of ET-1 in patients with chronic heart failure is increased and related to New York heart association class.(5) B-type natriuretic peptide, C-reactive protein, D-dimer, endothelial-1, fibrinogen exist inter-restriction and interference and maybe participate in pathophysiological process of chronic heart failure.更多还原