肥厚型梗阻性心肌病血液学标志物研究

发布时间：2018-03-24 02:32

本文选题：肌钙蛋白1　切入点：肥厚型梗阻性心肌病　出处：《北京协和医学院》2016年博士论文

【摘要】：第一部分：肥厚型梗阻性心肌病患者血清肌钙蛋白Ⅰ的临床意义与决定因素目的：血清肌钙蛋白已被证实对肥厚型心肌病(hypertrophic cardiomyopathy, HCM)患者的病情严重程度及预后判断中具有重要意义。然而,其在肥厚型梗阻性心肌病(hypertrophic obstructive cardiomyopathy, HOCM)中的意义还不明确。本研究旨在明确HOCM患者中血清肌钙蛋白Ⅰ(cardiac troponin I, cTnI)的临床意义与影响因素。方法：本研究测定149名HOCM患者血清cTnI水平,对其与临床表现、超声心动图及心脏磁共振参数进行相关性分析,并评估了其影响因素。结果：149名患者中位血清cTnI浓度为0.019 ng/ml(四分位距0.009-0.044 ng/m1)。其中,42名(28%)患者cTnI水平升高(≥0.04ng/ml)。cTnI水平升高者最大室壁厚度更厚(P0.001)、左室心肌质量指数(left ventricular mass index, LVMI)更大(P0.001)、左房≥50mm者更多(P=0.020)、血浆N末端B型利钠肽原(N-terminal pro-B-type natriuretic peptide, NT-proBNP)水平更高(P0.001)、且合并高血压者更少(P=0.014)。血清cTnI水平与最大室壁厚度(r= 0.444, P0.001), LVMI (r= 0.556, P0.001)、NT-proBNP(r= 0.305, P0.001)、左室舒张末期容积指数(r=0.246,P=0.002)和左室收缩末期容积指数(r=0.272,P=0.001)呈正相关,而与左室射血分数呈负相关(r=-0.180,P=0.028)。多因素分析表明,LVMI与血清cTnI水平升高独立相关(OR=1.032,P=0.001),与血清cTnI水平本身呈独立正相关(β=0.556,P0.001)；此外,合并高血压与血清cTnI水平升高可能性降低独立相关(OR=0.307,P=0.029),且与血清cTnI水平本身呈独立负相关(p=-0.165,P=0.015)。结论：本研究发现部分HOCM患者血清cTnI水平升高。血清cTnI与多种反映疾病严重程度的参数相关,提示其在评估HOCM患者的心脏重塑中具有重要意义。此外,LVMI所反映的左室肥厚程度是血清cTnI水平的主要影响因素。第二部分：血浆N末端B型利钠肽原与血清肌钙蛋白Ⅰ对肥厚型梗阻性心肌病患者心肌纤维化的预测价值目的：研究表明检测高敏肌钙蛋白T与B型利钠肽对判别肥厚型非梗阻性心肌病患者心肌纤维化[由心脏磁共振(cardiac magnetic resonance, CMR)延迟强化(late gadolinium enhancement, LGE)来测定]有益。然而,这些标志物在肥厚型梗阻性心肌病(hypertrophic obstructive cardiomyopathy, HOCM)中预测心肌纤维化的作用仍不明确。本研究通过测定循环N末端B型利钠肽原(N-terminal pro-B-type natriuretic peptide, NT-proBNP)与肌钙蛋白I (cardiac troponin I, cTnI)水平,以明确它们预测HOCM患者LGE的价值。方法：163名HOCM患者(年龄47.2±10.8岁,38.7%为女性)采集外周静脉血测定NT-proBNP与cTnI的水平。应用增强CMR对心肌纤维化进行定性(LGE阳性或阴性)及定量分析。对NT-proBNP及cTnI与心肌纤维化进行相关性分析,评估它们对心肌纤维化的预测价值。结果：163名患者中,120名(73.6%)LGE阳性。LGE阳性者NT-proBNP和cTnI水平比LGE阴性者显著升高[1386.2 (904.6-2340.8) vs.866.6 (707.2-1875.2) pmol/L, P=0.003；0.024(0.010-0.049)vs.0.01 0(0.005-0.021)ng/ml,P0.001]。LGE定量与logcTnI(r=0.371,P0.001)和log NT-proBNP (r= 0.211, P= 0.007)呈显著正相关。多变量分析显示, log cTnI和最大室壁厚度是LGE阳性的独立预测因素(OR=3.193,P=0.033；OR=1.410,P0.001),而log NT-proBNP不是。受试者工作特征曲线分析表明,最大室壁厚度≥21 mm和/或cTnI≥0.025ng/ml对LGE阳性有着良好的预测价值,特异性为95%,敏感性为88%。结论：血清cTnI是心肌纤维化的独立预测因子,而血浆NT-proBNP仅在单因素分析中与心肌纤维化有关。联合检测血清cTnI与最大室壁厚度可进一步提高其在预测HOCM患者心肌纤维化中的价值。第三部分：肥厚型梗阻性心肌病患者血清尿酸与左室心肌质量指数相关性的性别差异目的：血清尿酸(Serum uric acid, SUA)在多个不同研究人群中与左心室肥厚相关。然而,这种相关性是否同样存在于肥厚型梗阻性心肌病(hypertrophic obstructive cardiomyopathy, HOCM)患者中尚不清楚；此外,性别是否会对这种相关性产生影响亦不明确。本研究旨在探讨HOCM患者SUA与LVMI的相关性,及其性别差异。方法：本研究共纳入161名HOCM患者,平均年龄47.2±10.8岁,其中男性99名(62%)。所有患者均接受全面的临床、实验室、心脏超声及磁共振检查。左室心肌质量指数(left ventricular mass index, LVMI)通过心脏磁共振测定。结果：161名HOCM患者SUA平均值为353.4 ± 87.5 μmol/L。男性SUA浓度(381.2± 86.4 vs.309.0 ± 69.3 μmol/L, p 0.001)与LVMI (96.2 ± 32.1 vs.84.4 ± 32.4 g/m2, p=0.025)均较女性明显增加。按男女两性各自的SUA三分位数分别分为三组,女性LVMI随着SUA浓度的升高而明显升高(P=0.030),但男性无明显变化(P=0.177)。在女性中,SUA与LVMI呈显著正相关(r=0.372,P=0.003),但在男性中无关(r=0.112,P=0.269)。多因素线性回归分析显示,女性中SUA与LVMI独立相关(p=0.375,P=0.002),而在男性中无关。结论：SUA浓度与LVMI在女性HOCM患者中显著独立相关,但在男性中无关。提示降尿酸治疗措施可能会对HOCM(尤其是女性)患者有着潜在的重要意义。
[Abstract]:The first part: objective clinical significance and determinants of hypertrophic obstructive cardiomyopathy patients with serum cardiac troponin I, serum troponin has been confirmed of hypertrophic cardiomyopathy (hypertrophic cardiomyopathy, HCM) in patients with disease severity and prognosis has important significance. However, in patients with hypertrophic obstructive cardiomyopathy (hypertrophic obstructive cardiomyopathy, HOCM) the significance is not clear. The purpose of this study is to clear the serum cardiac troponin I in patients with HOCM (cardiac troponin I, cTnI) the clinical significance and influence factors. Methods: 149 patients with HOCM serum level of cTnI in this study, the clinical manifestations, echocardiography and cardiac magnetic resonance parameters and correlation analysis. The evaluation of the influencing factors. Results: 149 patients in the serum cTnI concentration of 0.019 ng/ml (four 0.009-0.044 ng/ from M1). Among them, 42 Name (28%) increased the level of cTnI in patients with elevated levels of.CTnI (more than 0.04ng/ml) the biggest wall thickness (P0.001), left ventricular mass index (left ventricular mass index, LVMI) more (P0.001), left atrial (P=0.020) more than 50mm, plasma N terminal B type natriuretic peptide (N-terminal pro-B-type natriuretic peptide, NT-proBNP) higher level (P0.001), and less complicated with hypertension (P=0.014). The serum level of cTnI and the maximum wall thickness (r= 0.444, P0.001), LVMI (r= 0.556, P0.001), NT-proBNP (r= 0.305, P0.001), left ventricular end diastolic volume index (r=0.246. P=0.002) and left ventricular end systolic volume index (r=0.272, P=0.001) were positively correlated, and negatively correlated with left ventricular ejection fraction (r=-0.180, P=0.028). Multivariate analysis showed that LVMI increased and the level of serum cTnI (OR=1.032, P=0.001) independent, is independently correlated with the serum level of cTnI itself (beta =0. 556, P0.001); in addition, hypertension and elevated serum cTnI levels to reduce the possibility of independent correlation (OR=0.307, P=0.029), and the serum level of cTnI itself were negatively correlated (p=-0.165, P=0.015). Conclusion: This study found that elevated serum cTnI levels in patients with HOCM. Serum cTnI and various parameters reflecting the severity of the disease related and that has important significance in the evaluation of patients with HOCM in cardiac remodeling. In addition, degree of left ventricular hypertrophy reflected by LVMI are the main factors affecting the level of serum cTnI. The second part: plasma N terminal B type natriuretic peptide and serum troponin I of predictive value in patients with hypertrophic obstructive cardiomyopathy, myocardial fibrosis Objective: studies show that Gao Min detection of troponin T and B type natriuretic peptide to identify non obstructive HCM patients with myocardial fibrosis by cardiac magnetic resonance (cardiac magnetic resonance, CMR) Delayed enhancement (late gadolinium enhancement, LGE)] to determine the beneficial. However, these markers in patients with hypertrophic obstructive cardiomyopathy (hypertrophic obstructive, cardiomyopathy, HOCM) in predicting myocardial fibrosis is still unclear. In this study, through the determination of circulating N terminal B type natriuretic peptide (N-terminal pro-B-type natriuretic peptide, NT-proBNP) and cardiac troponin I (cardiac troponin I, cTnI) level, to clarify their prediction in patients with HOCM the value of LGE. Methods: 163 HOCM patients (age 47.2 + 10.8 years, 38.7% women) peripheral venous blood was collected for NT-proBNP and cTnI. The application of enhanced CMR qualitative on myocardial fibrosis (LGE positive or negative) and quantitative analysis. Correlation analysis of NT-proBNP and cTnI and myocardial fibrosis, evaluate their predictive value on myocardial fibrosis. Results: of the 163 patients, 120 (73.6%) LGE The positive.LGE positive NT-proBNP and cTnI levels increased significantly than LGE negative [1386.2 (904.6-2340.8) vs.866.6 (707.2-1875.2) pmol/L, P=0.003; 0.024 (0.010-0.049) vs.0.01 0 (0.005-0.021) ng/ml, P0.001].LGE logcTnI and quantitative (r=0.371, P0.001) and log NT-proBNP (r= 0.211, P= 0.007) showed a significant positive correlation. Multivariate analysis according to log cTnI, and the maximum wall thickness is independently predicted LGE positive factors (OR=3.193, P=0.033; OR=1.410, P0.001), and log NT-proBNP. The receiver operating characteristic curve analysis showed that the maximum wall thickness more than 21 mm and / or cTnI = 0.025ng/ml for LGE positive has a good predictive value, specific as of 95%, the sensitivity was 88%. conclusion: serum cTnI is an independent predictor of myocardial fibrosis, and plasma NT-proBNP only in univariate analysis and myocardial fibrosis. The combined detection of serum cTnI and the maximum wall The thickness can further improve the prediction of HOCM in patients with myocardial fibrosis in value. The third part: gender differences in patients with hypertrophic obstructive cardiomyopathy, serum uric acid and left ventricular mass index Objective: correlation between serum uric acid (Serum uric, acid, SUA) in a number of different study population with left ventricular hypertrophy. However, this correlation it also exists in patients with hypertrophic obstructive cardiomyopathy (hypertrophic obstructive, cardiomyopathy, HOCM) patients is not clear; in addition, the gender will influence on this relationship is not clear. The purpose of this study is to investigate the correlation between SUA and LVMI in patients with HOCM, and the gender difference. Methods: This study included 161 patients with HOCM, the average age 47.2 + 10.8 years, of which 99 men (62%). All patients underwent a comprehensive clinical, laboratory, echocardiography and magnetic resonance imaging of left ventricular mass. Volume index (left ventricular mass index, LVMI) by cardiac magnetic resonance measurement. Results: 161 patients with HOCM SUA with an average of 353.4 + 87.5 mol/L. male SUA concentration (381.2 + 86.4 vs.309.0 + 69.3 mol/L, P 0.001) and LVMI (96.2 + 32.1 vs.84.4 + 32.4 g/m2, p=0.025) were lower than females according to their gender. SUA three percentiles were divided into three groups, women and LVMI increased significantly with the increase of SUA concentration (P=0.030), but no significant change (P=0.177) in men. In women, a significant positive correlation between SUA and LVMI (r=0.372, P=0.003), but not in men (r=0.112, P=0.269). Multivariate linear regression analysis showed that female SUA were independently associated with LVMI (p=0.375, P=0.002), but not in men. Conclusion: the concentration of SUA and LVMI in female patients with HOCM were significant independent, but in men. That urate lowering therapy measures It will have a potential significance for patients with HOCM (especially women).

【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R542.2

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