本文選題：肌鈣蛋白1　切入點(diǎn)：肥厚型梗阻性心肌病　出處：《北京協(xié)和醫(yī)學(xué)院》2016年博士論文

【摘要】：第一部分：肥厚型梗阻性心肌病患者血清肌鈣蛋白Ⅰ的臨床意義與決定因素目的：血清肌鈣蛋白已被證實(shí)對(duì)肥厚型心肌病(hypertrophic cardiomyopathy, HCM)患者的病情嚴(yán)重程度及預(yù)后判斷中具有重要意義。然而,其在肥厚型梗阻性心肌病(hypertrophic obstructive cardiomyopathy, HOCM)中的意義還不明確。本研究旨在明確HOCM患者中血清肌鈣蛋白Ⅰ(cardiac troponin I, cTnI)的臨床意義與影響因素。方法：本研究測定149名HOCM患者血清cTnI水平,對(duì)其與臨床表現(xiàn)、超聲心動(dòng)圖及心臟磁共振參數(shù)進(jìn)行相關(guān)性分析,并評(píng)估了其影響因素。結(jié)果：149名患者中位血清cTnI濃度為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)、左室心肌質(zhì)量指數(shù)(left ventricular mass index, LVMI)更大(P0.001)、左房≥50mm者更多(P=0.020)、血漿N末端B型利鈉肽原(N-terminal pro-B-type natriuretic peptide, NT-proBNP)水平更高(P0.001)、且合并高血壓者更少(P=0.014)。血清cTnI水平與最大室壁厚度(r= 0.444, P0.001), LVMI (r= 0.556, P0.001)、NT-proBNP(r= 0.305, P0.001)、左室舒張末期容積指數(shù)(r=0.246,P=0.002)和左室收縮末期容積指數(shù)(r=0.272,P=0.001)呈正相關(guān),而與左室射血分?jǐn)?shù)呈負(fù)相關(guān)(r=-0.180,P=0.028)。多因素分析表明,LVMI與血清cTnI水平升高獨(dú)立相關(guān)(OR=1.032,P=0.001),與血清cTnI水平本身呈獨(dú)立正相關(guān)(β=0.556,P0.001)；此外,合并高血壓與血清cTnI水平升高可能性降低獨(dú)立相關(guān)(OR=0.307,P=0.029),且與血清cTnI水平本身呈獨(dú)立負(fù)相關(guān)(p=-0.165,P=0.015)。結(jié)論：本研究發(fā)現(xiàn)部分HOCM患者血清cTnI水平升高。血清cTnI與多種反映疾病嚴(yán)重程度的參數(shù)相關(guān),提示其在評(píng)估HOCM患者的心臟重塑中具有重要意義。此外,LVMI所反映的左室肥厚程度是血清cTnI水平的主要影響因素。第二部分：血漿N末端B型利鈉肽原與血清肌鈣蛋白Ⅰ對(duì)肥厚型梗阻性心肌病患者心肌纖維化的預(yù)測價(jià)值目的：研究表明檢測高敏肌鈣蛋白T與B型利鈉肽對(duì)判別肥厚型非梗阻性心肌病患者心肌纖維化[由心臟磁共振(cardiac magnetic resonance, CMR)延遲強(qiáng)化(late gadolinium enhancement, LGE)來測定]有益。然而,這些標(biāo)志物在肥厚型梗阻性心肌病(hypertrophic obstructive cardiomyopathy, HOCM)中預(yù)測心肌纖維化的作用仍不明確。本研究通過測定循環(huán)N末端B型利鈉肽原(N-terminal pro-B-type natriuretic peptide, NT-proBNP)與肌鈣蛋白I (cardiac troponin I, cTnI)水平,以明確它們預(yù)測HOCM患者LGE的價(jià)值。方法：163名HOCM患者(年齡47.2±10.8歲,38.7%為女性)采集外周靜脈血測定NT-proBNP與cTnI的水平。應(yīng)用增強(qiáng)CMR對(duì)心肌纖維化進(jìn)行定性(LGE陽性或陰性)及定量分析。對(duì)NT-proBNP及cTnI與心肌纖維化進(jìn)行相關(guān)性分析,評(píng)估它們對(duì)心肌纖維化的預(yù)測價(jià)值。結(jié)果：163名患者中,120名(73.6%)LGE陽性。LGE陽性者NT-proBNP和cTnI水平比LGE陰性者顯著升高[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定量與logcTnI(r=0.371,P0.001)和log NT-proBNP (r= 0.211, P= 0.007)呈顯著正相關(guān)。多變量分析顯示, log cTnI和最大室壁厚度是LGE陽性的獨(dú)立預(yù)測因素(OR=3.193,P=0.033；OR=1.410,P0.001),而log NT-proBNP不是。受試者工作特征曲線分析表明,最大室壁厚度≥21 mm和/或cTnI≥0.025ng/ml對(duì)LGE陽性有著良好的預(yù)測價(jià)值,特異性為95%,敏感性為88%。結(jié)論：血清cTnI是心肌纖維化的獨(dú)立預(yù)測因子,而血漿NT-proBNP僅在單因素分析中與心肌纖維化有關(guān)。聯(lián)合檢測血清cTnI與最大室壁厚度可進(jìn)一步提高其在預(yù)測HOCM患者心肌纖維化中的價(jià)值。第三部分：肥厚型梗阻性心肌病患者血清尿酸與左室心肌質(zhì)量指數(shù)相關(guān)性的性別差異目的：血清尿酸(Serum uric acid, SUA)在多個(gè)不同研究人群中與左心室肥厚相關(guān)。然而,這種相關(guān)性是否同樣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,性別是否會(huì)對(duì)這種相關(guān)性產(chǎn)生影響亦不明確。本研究旨在探討HOCM患者SUA與LVMI的相關(guān)性,及其性別差異。方法：本研究共納入161名HOCM患者,平均年齡47.2±10.8歲,其中男性99名(62%)。所有患者均接受全面的臨床、實(shí)驗(yàn)室、心臟超聲及磁共振檢查。左室心肌質(zhì)量指數(shù)(left ventricular mass index, LVMI)通過心臟磁共振測定。結(jié)果：161名HOCM患者SUA平均值為353.4 ± 87.5 μmol/L。男性SUA濃度(381.2± 86.4 vs.309.0 ± 69.3 μmol/L, p 0.001)與LVMI (96.2 ± 32.1 vs.84.4 ± 32.4 g/m2, p=0.025)均較女性明顯增加。按男女兩性各自的SUA三分位數(shù)分別分為三組,女性LVMI隨著SUA濃度的升高而明顯升高(P=0.030),但男性無明顯變化(P=0.177)。在女性中,SUA與LVMI呈顯著正相關(guān)(r=0.372,P=0.003),但在男性中無關(guān)(r=0.112,P=0.269)。多因素線性回歸分析顯示,女性中SUA與LVMI獨(dú)立相關(guān)(p=0.375,P=0.002),而在男性中無關(guān)。結(jié)論：SUA濃度與LVMI在女性HOCM患者中顯著獨(dú)立相關(guān),但在男性中無關(guān)。提示降尿酸治療措施可能會(huì)對(duì)HOCM(尤其是女性)患者有著潛在的重要意義。
[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).

【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R542.2

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