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慢性心力衰竭是临床老年病人死亡的主要心脏病因之一, 其发病率和死亡率呈逐年增长趋势,并且病人的预后较差,对人们的生命健康造成严重威胁[1-2]。目前慢性心力衰竭病人的心力衰竭严重程度主要通过纽约心脏协会(New York Heart Association,NYHA)的心功能分级标准进行评估,但是该评判标准主要依赖于病人的自觉症状,诊断准确性较差[3]。近年来随着血清学检测技术的不断发展,通过血清学检测对慢性心力衰竭进行诊断和预后评估逐渐得到广泛关注。人附睾蛋白4(human epididymis protein 4,HE4)是卵巢癌的肿瘤标志物分子,参与调节肿瘤炎症反应,正常组织细胞中HE4表达水平较低,在病理条件下HE4水平明显升高[4]。胱抑素C(Cystatin C)主要分布于肝、肾和肌肉等组织中,是半胱氨酸蛋白酶抑制剂,能够抑制半胱氨酸蛋白酶的催化活性,在冠状动脉综合征和高血压病人中Cystatin C水平明显上调,在心脑血管疾病的诊断中具有一定临床价值[5-6]。脑钠肽(brain natriuretic peptide, BNP)主要由脑分泌产生,能够调节血压和血容量,在急性心肌梗死和心功能障碍等心脑血管疾病病人中BNP水平升高,并且与病人的病情严重程度密切相关[7-8]。目前对于慢性心力衰竭的血清学诊断仍然缺乏准确有效的生化指标,本研究通过检测血清HE4、Cystatin C及BNP水平,旨在探讨其在慢性心力衰竭病人中的水平及其与心力衰竭严重程度及预后的关系,现作报道。
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不同心功能分级慢性心力衰竭病人血清HE4、Cystatin C及BNP水平均明显高于对照组,且随着心功能分级的升高,血清HE4、Cystatin C及BNP水平逐渐升高,差异均有统计学意义(P<0.01)(见表 1)。
分组 n HE4/(ng/mL) Cystatin C/(ng/mL) BNP/(ng/mL) 对照组 75 50.18±8.23 0.69±0.11 65.04±10.66 心功能Ⅱ级 24 61.49±9.04** 1.16±0.17** 102.76±15.11** 心功能Ⅲ级 53 74.81±11.87**## 1.42±0.23**## 148.58±23.58**## 心功能Ⅳ级 43 95.69±14.72**##△△ 1.96±0.30**##△△ 209.43±32.22**##△△ F — 164.48 368.37 456.13 P — < 0.01 < 0.01 < 0.01 MS组内 — 122.088 0.042 451.175 q检验:与对照组比较**P<0.01;与心功能Ⅱ级比较##P<0.01;与心功能Ⅲ级比较△△P<0.01 表 1 不同心功能分级病人与对照组血清HE4、Cystatin C及BNP水平比较(x±s)
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死亡组与存活组的性别、年龄、BMI、吸烟史、总胆固醇、三酰甘油、HDL、LDL和空腹血糖比较,差异均无统计学意义(P>0.05)。死亡组的血清HE4、Cystatin C及BNP水平均明显高于存活组,而LVEF明显低于存活组,差异有统计学意义(P<0.01)(见表 2)。
临床资料 死亡组(n=31) 存活组(n=89) t P 性别 男
女18
1349
400.08* >0.05 年龄/岁 61.08±10.01 62.49±9.19 0.72 >0.05 BMI/(kg/m2) 23.59±1.22 24.08±1.19 1.96 >0.05 吸烟史 有
无18
1351
380.01* >0.05 总胆固醇/(mmol/L) 4.24±0.70 4.31±0.63 0.52 >0.05 三酰甘油/(mmol/L) 1.64±0.27 1.58±0.23 1.19 >0.05 HDL/(mmol/L) 1.32±0.22 1.37±0.20 1.17 >0.05 LDL/(mmol/L) 2.63±0.43 2.51±0.37 1.49 >0.05 空腹血糖/(mmol/L) 5.27±1.05 5.69±1.29 1.63 >0.05 HE4/(ng/mL) 85.71±14.05 76.66±11.27 3.60 < 0.01 Cystatin C/(ng/mL) 1.86±0.30 1.51±0.22 6.84 < 0.01 BNP/(ng/mL) 225.69±37.00 180.27±26.51 7.38 < 0.01 LVEF/% 40.39±6.62 54.70±8.04 8.90 < 0.01 *示χ2值 表 2 慢性心力衰竭病人死亡组与存活组相关临床资料比较(x±s)
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以病人是否死亡作为因变量,表 2中有统计学意义的变量为自变量进行多因素逐步logistic回归分析(α入=0.05,α出=0.10),结果显示,血清HE4、Cystatin C及BNP是慢性心力衰竭病人预后的主要危险因素(OR=1.999、2.333、1.809,P<0.01),LVEF是慢性心力衰竭病人预后的保护因素(OR=0.734,P<0.01)(见表 3)。
变量 B SE Waldχ2 P OR 95%CI HE4 0.695 0.109 12.32 < 0.01 1.999 1.241~3.189 Cystatin C 0.851 0.138 13.46 < 0.01 2.333 1.584~3.191 BNP 0.739 0.089 10.33 < 0.01 1.809 1.233~3.197 LVEF -0.806 0.076 10.05 < 0.01 0.734 0.418~0.931 表 3 慢性心力衰竭病人死亡的多因素logistic回归分析
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采用ROC曲线评估血清HE4、Cystatin C和BNP以及LVEF对病人预后的预测价值,结果显示,血清HE4、Cystatin C及BNP联合LVEF预测病人不良预后的价值高于各指标单独预测价值(见图 1、见表 4)。
变量 曲线下面积 P 95%CI 敏感性/% 特异性/% 最佳截断值 HE4 0.663 < 0.01 0.660~0.676 78.1 76.9 60.46 ng/mL Cystatin C 0.752 < 0.01 0.701~0.761 81.1 80.6 1.58 ng/mL BNP 0.825 < 0.01 0.803~0.861 86.1 85.7 186.74 ng/mL LVEF 0.783 < 0.01 0.742~0.809 84.2 82.5 57.24% 联合 0.962 < 0.01 0.901~0.992 92.2 90.7 - 表 4 血清HE4、Cystatin C和BNP及LVEF对病人预后的预测价值
血清HE4、Cystatin C及BNP与慢性心力衰竭病人心力衰竭严重程度及预后的相关性分析
Correlation analysis of serum HE4, Cystatin C and BNP with the severity and prognosis of heart failure in patients with chronic heart failure
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摘要:
目的探讨血清人附睾蛋白4(HE4)、胱抑素C(Cystatin C)和脑钠肽(BNP)与慢性心力衰竭病人的心力衰竭严重程度及预后的相关性。 方法收集120例慢性心力衰竭病人为研究对象。根据纽约心脏协会(NYHA)的心功能分级标准分为心功能Ⅱ级24例、Ⅲ级53例、Ⅳ级43例。根据病人是否死亡将病人进一步分为31例死亡组和89例存活组,并于同期随机选取75名健康体检者为对照组。采用酶联免疫吸附法检测各组血清HE4、Cystatin C及BNP水平,比较死亡组与存活组的各项临床指标。 结果心功能Ⅳ级病人血清HE4、Cystatin C及BNP水平最高,其次为心功能Ⅲ级和心功能Ⅱ级,对照组最低(P<0.01)。与存活组相比,死亡组血清HE4、Cystatin C及BNP水平明显升高,左心室射血分数(LVEF)明显明显下降(P<0.01)。血清HE4、Cystatin C及BNP是病人预后的主要危险因素(OR=1.999、2.333、1.809, P<0.01),而LVEF是保护因素(OR=0.734,P<0.01)。血清HE4、Cystatin C及BNP联合LVEF检测对病人预后的预测价值高于各指标单独检测。 结论血清HE4、Cystatin C及BNP水平升高与慢性心力衰竭病人的病情严重程度及预后密切相关,三项指标联合LVEF检测有助于预测不良预后发生风险,在慢性心力衰竭病人的诊治中具有一定临床价值。 Abstract:ObjectiveTo investigate the correlation of serum human epididymal protein 4 (HE4), Cystatin C and brain natriuretic peptide (BNP) with the severity and prognosis of heart failure in patients with chronic heart failure. MethodsA total of 120 patients with chronic heart failure were collected as subjects.According to the NYHA classification standard, patients were divided into 24 cases of class Ⅱ, 53 cases of class Ⅲ and 43 cases of class Ⅳ.The patients were further divided into death group(n=31) and survival group(n=89) according to the death.Seventy-five healthy patients were randomly selected as the control group at the same time.Serum levels of HE4, Cystatin C and BNP in each group were determined by enzyme-linked immunosorbent assay. ResultsSerum HE4, Cystatin C and BNP level in class Ⅳ patients were the highest, followed by class Ⅲ and Ⅱ, control group was the lowest (P<0.01).Compared with the control group, serum HE4, Cystatin C and BNP levels in the control group were significantly increased, and LVEF was significantly decreased (P<0.01).Serum HE4, Cystatin C and BNP were the major risk factors for poor prognosis (OR=1.999, 2.333, 1.809, P<0.01), while LVEF was the protective factor (OR=0.734, P<0.01).The predictive value of serum HE4, Cystatin C and BNP combined with LVEF was higher than those of each individual test. ConclusionsElevated serum HE4, Cystatin C and BNP levels are closely related to the severity and prognosis of patients with chronic heart failure.The combination of three indicators and LVEF test is helpful to predict the risk of poor prognosis, which has certain clinical value in the diagnosis and treatment of chronic heart failure. -
表 1 不同心功能分级病人与对照组血清HE4、Cystatin C及BNP水平比较(x±s)
分组 n HE4/(ng/mL) Cystatin C/(ng/mL) BNP/(ng/mL) 对照组 75 50.18±8.23 0.69±0.11 65.04±10.66 心功能Ⅱ级 24 61.49±9.04** 1.16±0.17** 102.76±15.11** 心功能Ⅲ级 53 74.81±11.87**## 1.42±0.23**## 148.58±23.58**## 心功能Ⅳ级 43 95.69±14.72**##△△ 1.96±0.30**##△△ 209.43±32.22**##△△ F — 164.48 368.37 456.13 P — < 0.01 < 0.01 < 0.01 MS组内 — 122.088 0.042 451.175 q检验:与对照组比较**P<0.01;与心功能Ⅱ级比较##P<0.01;与心功能Ⅲ级比较△△P<0.01 表 2 慢性心力衰竭病人死亡组与存活组相关临床资料比较(x±s)
临床资料 死亡组(n=31) 存活组(n=89) t P 性别 男
女18
1349
400.08* >0.05 年龄/岁 61.08±10.01 62.49±9.19 0.72 >0.05 BMI/(kg/m2) 23.59±1.22 24.08±1.19 1.96 >0.05 吸烟史 有
无18
1351
380.01* >0.05 总胆固醇/(mmol/L) 4.24±0.70 4.31±0.63 0.52 >0.05 三酰甘油/(mmol/L) 1.64±0.27 1.58±0.23 1.19 >0.05 HDL/(mmol/L) 1.32±0.22 1.37±0.20 1.17 >0.05 LDL/(mmol/L) 2.63±0.43 2.51±0.37 1.49 >0.05 空腹血糖/(mmol/L) 5.27±1.05 5.69±1.29 1.63 >0.05 HE4/(ng/mL) 85.71±14.05 76.66±11.27 3.60 < 0.01 Cystatin C/(ng/mL) 1.86±0.30 1.51±0.22 6.84 < 0.01 BNP/(ng/mL) 225.69±37.00 180.27±26.51 7.38 < 0.01 LVEF/% 40.39±6.62 54.70±8.04 8.90 < 0.01 *示χ2值 表 3 慢性心力衰竭病人死亡的多因素logistic回归分析
变量 B SE Waldχ2 P OR 95%CI HE4 0.695 0.109 12.32 < 0.01 1.999 1.241~3.189 Cystatin C 0.851 0.138 13.46 < 0.01 2.333 1.584~3.191 BNP 0.739 0.089 10.33 < 0.01 1.809 1.233~3.197 LVEF -0.806 0.076 10.05 < 0.01 0.734 0.418~0.931 表 4 血清HE4、Cystatin C和BNP及LVEF对病人预后的预测价值
变量 曲线下面积 P 95%CI 敏感性/% 特异性/% 最佳截断值 HE4 0.663 < 0.01 0.660~0.676 78.1 76.9 60.46 ng/mL Cystatin C 0.752 < 0.01 0.701~0.761 81.1 80.6 1.58 ng/mL BNP 0.825 < 0.01 0.803~0.861 86.1 85.7 186.74 ng/mL LVEF 0.783 < 0.01 0.742~0.809 84.2 82.5 57.24% 联合 0.962 < 0.01 0.901~0.992 92.2 90.7 - -
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