血清同型半胱氨酸、甲硫氨酸和半胱氨酸与慢性心力衰竭的相关性分析

Correlation analysis of the serum homocysteine, methionine and cysteine in patients with chronic heart failure

目的分析血清同型半胱氨酸(Hcy)、甲硫氨酸(Met)和半胱氨酸(Cys)与慢性心力衰竭(CHF)的相关性及诊断价值。方法连续纳入2018年10月至2019年9月大连大学附属中山医院178例CHF急性加重期患者(CHF组)和70例健康体检者(健康对照组)。CHF组中,射血分数降低的心力衰竭(HFrEF)53例,射血分数中间值的心力衰竭(HFmrEF)50例,射血分数保留的心力衰竭(HFpEF)75例。采用串联质谱法检测血清Hcy、Met和Cys;电化学发光免疫技术检测血清N末端脑钠肽前体(NT-proBNP);超声心动图检测左心室舒张末期内径(LVEDd)、左心室收缩末期内径(LVESd)和二尖瓣口舒张早期血流峰值速度与二尖瓣环舒张早期运动峰值速度比值(E/e′),计算左心室射血分数(LVEF)。相关性采用Pearson相关分析。绘制受试者工作特征(ROC)曲线,利用曲线下面积(AUC)评价血清Hcy、Met、Cys、NT-proBNP、LVEF诊断CHF的效能。结果CHF组Hcy、Met、Cys、NT-proBNP、LVEDd和E/e′明显高于健康对照组[(12.64±5.02)μmol/L比(8.71±3.47)μmol/L、(23.38±5.75)μmol/L比(20.52±4.18)μmol/L、(343.45±44.49)μmol/L比(290.53±48.38)μmol/L、(5759.43±3806.22)pg/L比(40.24±31.91)pg/L、(52.67±12.27)mm比(46.41±12.27)mm和(17.32±5.61)%比(9.54±2.64)%],LVEF明显低于健康对照组[(45.27±4.93)%比(62.37±5.41)%],差异有统计学意义(P<0.01或<0.05)。HFmrEF和HFrEF患者血清Hcy和Cys明显高于HFpEF患者[(16.29±8.18)和(18.68±8.99)μmol/L比(13.75±6.48)μmol/L、(346.64±51.85)和(361.40±52.34)μmol/L比(329.35±55.16)μmol/L],差异有统计学意义(P<0.05);HFmrEF患者与HFrEF患者比较差异无统计学意义(P>0.05)。HFrEF患者血清Met明显高于HFpEF和HFmrEF患者[(28.74±8.22)μmol/L比(24.76±7.60)和(25.15±6.96)μmol/L],差异有统计学意义(P<0.05);HFpEF患者与HFmrEF患者比较差异无统计学意义(P>0.05)。Pearson相关性分析结果显示,Hcy、Met、Cys与NT-proBNP呈正相关(r=0.632、0.206和0.455,P<0.01),与E/e′水平呈正相关(r=0.463、0.198和0.346,P<0.01),与LVEF呈负相关(r=-0.491、-0.152和-0.330,P<0.05或<0.01)。ROC曲线分析结果显示,根据最大约登指数(0.994)确定血清NT-proBNP诊断CHF的最佳临界值为120 pg/L,AUC为0.994,95%CI 0.997~1.000;根据最大约登指数(0.646)确定Hcy诊断CHF的最佳临界值为10.56μmol/L,AUC为0.899,95%CI 0.859~0.939;根据最大约登指数(0.218)确定Met诊断CHF的最佳临界值为25.58μmol/L,AUC为0.637,95%CI 0.563~0.711;根据最大约登指数(0.391)确定Cys诊断CHF的最佳临界值为298.05μmol/L,AUC为0.765,95%CI 0.700~0.830;LVEF的AUC<0.5。结论CHF患者血清Hcy、Met、Cys水平明显升高,与NT-proBNP及E/e′水平呈正相关,与LVEF水平呈负相关,血清Hcy水平对于CHF的诊断有一定应用价值。

Objective To analyze the correlation and diagnostic value of serum homocysteine(Hcy),methionine(Met)and cysteine(Cys)in patients with chronic heart failure(CHF).Methods One hundred and seventy-eight patients with acute decompensation CHF(CHF group)and 70 healthy persons(healthy control group)from October 2018 to September 2019 in Affiliated Zhongshan Hospital of Dalian University were continuously enrolled.In CHF group,heart failure with reduced ejection fraction(HFrEF)was in 53 cases,heart failure with mid-range ejection fraction(HFmrEF)was in 50 cases,and heart failure with preserved ejection fraction(HFpEF)was in 75 cases.Serum levels of Hcy,Met and Cys were detected by tandem mass spectrometry.Serum level of N-terminal brain natriuretic peptide precursor(NT-proBNP)was detected by electrochemical luminescence immunity.The left ventricular end-diastolic diameter(LVEDd),left ventricular end-systolic diameter(LVESd)and early diastolic peak blood flow velocity of mitral valve annulus/early diastolic peak velocity of mitral annulus(E/e′)were detected by echocardiography,then left ventricular eject fraction(LVEF)was calculated.Correlation was analyzed by Pearson correlation analysis.The receiver operator characteristic(ROC)curve was drawn,and the area under curve(AUC)was used to evaluate the efficacy of serum Hcy,Met,Cys,NT-proBNP and LVEF in the diagnosis of CHF.Results The Hcy,Met,Cys,NT-proBNP,LVEDd and E/e′in CHF group were significantly higher than those in healthy control group:(12.64±5.02)μmol/L vs.(8.71±3.47)μmol/L,(23.38±5.75)μmol/L vs.(20.52±4.18)μmol/L,(343.45±44.49)μmol/L vs.(290.53±48.38)μmol/L,(5759.43±3806.22)pg/L vs.(40.24±31.91)pg/L,(52.67±12.27)mm vs.(46.41±12.27)mm and(17.32±5.61)%vs.(9.54±2.64)%,the LVEF was significantly lower than that in healthy control group:(45.27±4.93)%vs.(62.37±5.41)%,and there were statistical differences(P<0.01 or<0.05).The Hcy and Cys in patients with HFmrEF and HFrEF were significantly higher than those in patients with HFpEF:(16.29±8.18)and(18.68±8.99)μmol/L vs.(13.75±6.48)μmol/L,(346.64±51.85)and(361.40±52.34)μmol/L vs.(329.35±55.16)μmol/L,and there were statistical differences(P<0.05);there were no statistical differences between patients with HFmrEF and patients with HFrEF(P>0.05).The serum Met in patients with HFrEF was significantly higher than that in patients with HFpEF and HFmrEF:(28.74±8.22)μmol/L vs.(24.76±7.60)and(25.15±6.96)μmol/L,and there was statistical difference(P<0.05);there was no statistical difference between patients with HFpEF and patients with HFmrEF(P>0.05).Pearson correlation analysis result showed that serum Hcy,Met and Cys were positively correlated with NT-proBNP(r=0.632,0.206 and 0.455;P<0.01),positively correlated with E/e′(r=0.463,0.198 and 0.346;P<0.01),and negatively correlated with LVEF(r=-0.491,-0.152 and-0.330;P<0.05 or<0.01).ROC curve analysis result showed that ROC the cut-off value for the diagnosis of CHF with serum NT-proBNP based on the maximum Youden index(0.994)was 120 pg/L,and AUC was 0.994(95%CI was 0.997 to 1.000);the cut-off value for the diagnosis of CHF with serum Hcy based on the maximum Youden index(0.646)was 10.56μmol/L,and AUC was 0.899(95%CI 0.859 to 0.939);the cut-off value for the diagnosis of CHF with serum Met based on the maximum Youden index(0.218)was 25.58μmol/L,and AUC was 0.637(95%CI 0.563 to 0.711);the cut-off value for the diagnosis of CHF with serum Cys based on the maximum Youden index(0.391)was 298.05μmol/L,and AUC was 0.765(95%CI 0.700 to 0.830);the AUC of LVEF less than 0.5.Conclusions Serum Hcy,Met and Cys levels in patient with CHF are significantly increased,which are positively correlated with NT-proBNP and E/e′,negatively correlated with LVEF.Moreover,serum Hcy has certain application value in the diagnosis of CHF.