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原发性肝癌干预前并发心肌损伤的危险因素及列线图模型构建

邓玲芬,  向劲宇,  常丽仙,  王颖玲,  姬文静,  刘春云,  刘立

引用本文:
Citation:

原发性肝癌干预前并发心肌损伤的危险因素及列线图模型构建

DOI: 10.12449/JCH260919
基金项目: 

昆明市科技计划项目 (2024-1-NS-0035)

伦理学声明:本研究方案于2026年1月5日经由昆明市第三人民医院伦理委员会审批通过,伦理批号:KSYXLL202601-006。
利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:邓玲芬、向劲宇负责收集分析资料,撰写论文;常丽仙、王颖玲和姬文静负责收集数据;刘春云、刘立负责指导写作思路并最后定稿。
详细信息
    通信作者:

    刘立, liuli197210@163.com (ORCID: 0000-0001-7712-4931)

Risk factors for concurrent myocardial injury before intervention in patients with primary hepatic carcinoma and construction of a nomogram prediction model

Research funding: 

Project of the Science and Technology Plan of Kunming City (2024-1-NS-0035)

More Information
  • 摘要:   目的  探讨原发性肝癌(PHC)患者干预前并发心肌损伤的独立危险因素,构建并验证可早期识别此类患者的列线图,为临床早期防治提供依据。  方法  回顾性收集2019年1月—2025年6月两所医疗机构1 822例PHC患者的临床资料,其中来自昆明市第三人民医院的1 518例作为训练集,用于构建模型;来自保山市第二人民医院的304例作为验证集。根据PHC患者干预前高灵敏度心肌肌钙蛋白T检测结果,将患者分为心肌损伤组和非心肌损伤组。采用单因素、LASSO回归及多因素Logistic回归分析PHC患者干预前并发心肌损伤的危险因素,并据此构建预测模型。通过304例验证集患者的独立数据进行外部验证,使用受试者操作特征曲线下面积(AUC)、Hosmer-Lemeshow拟合优度检验、校准曲线、临床决策曲线及临床影响曲线评价模型性能。  结果  训练集中,心肌损伤组346例,非心肌损伤组1 172例,并发心肌损伤患病率22.79%。年龄(56.44±9.45)岁、男性占81.49%、饮酒者占49.34%、吸烟者占57.44%、慢性乙型肝炎患者占61.73%、慢性丙型肝炎患者占32.48%、高血压者占22.66%、糖尿病者占17.19%、蔡尔德-皮尤分级A级者占50.53%、巴塞罗那肝癌临床分期B期者占33.86%、心电图异常者占62.12%。单因素、LASSO回归及多因素Logistic回归分析结果显示,年龄[比值比(OR)=1.051,95%置信区间(CI):1.036~1.067,P<0.001]、糖尿病史(OR=1.862,95%CI:1.346~2.574,P<0.001)、心电图(OR=1.446,95%CI:1.077~1.940,P=0.014)、血红蛋白(HGB)(OR=0.993,95%CI:0.988~0.998,P=0.003)、白蛋白(Alb)(OR=0.951,95%CI:0.930~0.972,P<0.001)、肌酐(Cr)(OR=1.021,95%CI:1.016~1.026,P<0.001)是PHC患者发生心肌损伤的独立影响因素,据此建立回归方程:Logit(Y)=-3.406+0.050×年龄+0.621×糖尿病史+0.369×心电图-0.007×HGB-0.051×Alb+0.021×Cr,以此建立列线图。模型验证结果显示:Bootstrap内部验证AUC为0.743(95%CI:0.707~0.778),训练集AUC为0.766(95%CI:0.738~0.794),验证集AUC为0.730(95%CI:0.688~0.793)。Hosmer-Lemeshow拟合优度检验结果显示,训练集的P值为0.716,验证集P值为0.408,提示模型拟合良好。训练集和验证集的校准曲线、临床决策曲线及临床影响曲线均表明,该模型具有良好的临床应用价值。  结论  年龄、糖尿病史、心电图、HGB、Alb和Cr是预测PHC患者并发心肌损伤的6个独立影响因素,基于上述指标构建的列线图具有良好的区分度、准确性和临床实用性。

     

  • 注: a,LASSO回归系数路径图;b,10倍交叉验证曲线。

    图  1  基于LASSO回归的变量筛选

    Figure  1.  Variable selection based on LASSO regression

    注: HGB,血红蛋白;Alb,白蛋白;Cr,肌酐;PHC,原发性肝癌。

    图  2  预测PHC干预前并发心肌损伤风险的列线图

    Figure  2.  Nomogram for predicting the risk of myocardial injury prior to intervention in patients with PHC

    注: a,训练集;b,验证集。PHC,原发性肝癌;ROC曲线,受试者操作特征曲线;AUC,曲线下面积;CI,置信区间。

    图  3  训练集与验证集PHC患者并发心肌损伤预测模型的ROC曲线

    Figure  3.  ROC curves of the prediction model for myocardial injury in PHC patients in the training set and validation set

    注: a,训练集;b,验证集。PHC,原发性肝癌。

    图  4  训练集与验证集PHC患者并发心肌损伤预测模型的校准曲线

    Figure  4.  Calibration curves of the prediction model for myocardial injury in PHC patients in the training set and validation set

    注: a,训练集;b,验证集。PHC,原发性肝癌。

    图  5  训练集与验证集PHC患者并发心肌损伤预测模型的临床决策曲线

    Figure  5.  Clinical decision curve analysis of the prediction model for myocardial injury in patients with PHC in the training set and validation set

    注: a,训练集;b,验证集。PHC,原发性肝癌。

    图  6  训练集与验证集PHC患者并发心肌损伤预测模型的临床影响曲线

    Figure  6.  Clinical impact curve of the prediction model for myocardial injury in patients with PHC in the training set and validation set

    表  1  训练集心肌损伤组与非心肌损伤组基线资料比较

    Table  1.   Comparison of baseline characteristics between the myocardial injury group and the non-myocardial injury group in training set

    项目 非心肌损伤组(n=1 172) 心肌损伤组(n=346) 统计值 P值
    年龄(岁) 55.44±9.15 59.82±9.69 t=-7.730 <0.001
    性别[例(%)] χ2=0.094 0.759
    男 957(81.66) 280(80.92)
    女 215(18.34) 66(19.08)
    饮酒史[例(%)] χ2=0.794 0.373
    无 601(51.28) 168(48.55)
    有 571(48.72) 178(51.45)
    吸烟史[例(%)] χ2=0.047 0.828
    无 497(42.41) 149(43.06)
    有 675(57.59) 197(56.94)
    CHB[例(%)] χ2=2.919 0.088
    无 435(37.12) 146(42.20)
    有 737(62.88) 200(57.80)
    CHC[例(%)] χ2=2.207 0.137
    无 780(66.55) 245(70.81)
    有 392(33.45) 101(29.19)
    高血压史[例(%)] χ2=12.917 <0.001
    无 931(79.44) 243(70.23)
    有 241(20.56) 103(29.77)
    糖尿病史[例(%)] χ2=15.795 <0.001
    无 995(84.90) 262(75.72)
    有 177(15.10) 84(24.28)
    Child-Pugh分级[例(%)] χ2=56.310 <0.001
    A级 651(55.55) 116(33.53)
    B级 357(30.46) 141(40.75)
    C级 164(13.99) 89(25.72)
    BCLC分期[例(%)] χ2=48.945 <0.001
    0期 215(18.34) 33(9.54)
    A期 194(16.55) 31(8.96)
    B期 396(33.79) 118(34.10)
    C期 202(17.24) 73(21.10)
    D期 165(14.08) 91(26.30)
    心电图[例(%)] χ2=24.272 <0.001
    正常 483(41.21) 92(26.59)
    异常 689(58.79) 254(73.41)

    注:CHB,慢性乙型肝炎;CHC,慢性丙型肝炎;Child-Pugh分级,蔡尔德-皮尤分级;BCLC分期,巴塞罗那肝癌临床分期。

    下载: 导出CSV

    表  2  训练集心肌损伤组与非心肌损伤组实验室指标比较

    Table  2.   Comparison of laboratory parameters between the myocardial injury group and the non-myocardial injury group

    项目 非心肌损伤组(n=1 172) 心肌损伤组(n=346) 统计值 P值
    WBC(×109/L) 4.41(3.32~6.08) 5.07(3.70~7.20) Z=-4.405 <0.001
    NEUT(×109/L) 2.34(1.54~3.64) 2.88(1.59~4.92) Z=-3.925 <0.001
    LYM(×109/L) 1.17(0.77~1.72) 0.98(0.64~1.59) Z=-3.240 0.001
    HGB(g/L) 132.05±32.39 116.58±33.22 t=7.760 <0.001
    PLT(×109/L) 108.00(72.00~163.00) 107.00(70.75~182.25) Z=-0.821 0.412
    PCT(ng/mL) 0.10(0.05~0.26) 0.21(0.09~0.66) Z=-8.140 <0.001
    hs-CRP(mg/mL) 4.56(1.14~17.69) 11.32(2.84~36.42) Z=-6.892 <0.001
    PT(s) 15.10(14.10~16.50) 15.90(14.40~18.00) Z=-4.971 <0.001
    FIB(g/L) 2.67(2.11~3.42) 2.61(1.87~3.55) Z=-0.782 0.434
    AFP(ng/mL) 16.24(3.97~665.97) 36.68(4.14~2 050.25) Z=-2.351 0.019
    CEA(ng/mL) 2.98(1.96~4.55) 3.56(2.35~5.08) Z=-4.069 <0.001
    TBil(μmol/L) 22.40(14.90~38.98) 27.90(16.78~59.40) Z=-4.400 <0.001
    AST(U/L) 45.00(31.00~82.00) 58.50(36.00~115.00) Z=-4.616 <0.001
    ALT(U/L) 34.00(22.00~54.00) 37.00(21.00~64.00) Z=-1.937 0.053
    Alb(g/L) 35.00(29.40~40.10) 30.30(25.50~35.60) Z=-9.003 <0.001
    GGT(U/L) 84.00(42.00~186.00) 114.25(57.75~232.50) Z=-4.192 <0.001
    ALP(U/L) 140.50(101.00~207.00) 162.00(116.75~251.25) Z=-4.835 <0.001
    ChE(U/L) 4 352.50(2 825.00~6 313.75) 3 133.50(1 923.00~4 836.50) Z=-7.350 <0.001
    TBA(μmol/L) 15.60(5.50~42.25) 23.25(7.58~63.83) Z=-3.841 <0.001
    TG(mmol/L) 0.89(0.66~1.29) 0.93(0.66~1.32) Z=-0.338 0.735
    TC(mmol/L) 3.73(3.10~4.42) 3.49(2.79~4.40) Z=-2.978 0.003
    LDL(mmol/L) 2.26(1.75~2.89) 2.15(1.52~2.94) Z=-1.625 0.104
    Cr(μmol/L) 60.00(49.00~72.00) 71.00(56.00~95.00) Z=-8.581 <0.001
    BA(μmol/L) 31.85(21.00~45.13) 36.60(22.75~53.40) Z=-3.740 <0.001
    CD4+(个/μL) 397.17(269.58~583.03) 367.96(245.93~544.07) Z=-2.246 0.025
    CD8+(个/μL) 242.58(139.59~395.35) 222.04(122.34~362.47) Z=-2.014 0.044
    CD4+/CD8+ 1.69(1.16~2.33) 1.74(1.21~2.50) Z=-1.304 0.192
    IL-6(pg/mL) 11.93(4.91~29.80) 22.66(7.90~62.27) Z=-6.524 <0.001
    TNF-α(pg/mL) 2.45(1.48~5.87) 2.96(1.71~7.42) Z=-2.371 0.018

    注:WBC,白细胞计数;NEUT,中性粒细胞计数;LYM,淋巴细胞计数;PLT,血小板;HGB,血红蛋白;PCT,降钙素原;hs-CRP,超敏C反应蛋白;PT,凝血酶原时间;FIB,纤维蛋白原;AFP,甲胎蛋白;CEA,癌胚抗原;TBil,总胆红素;AST,天冬氨酸氨基转移酶;ALT,丙氨酸氨基转移酶;Alb,白蛋白;GGT,γ-谷氨酰转移酶;ALP,碱性磷酸酶;ChE,胆碱酯酶;TBA,总胆汁酸;TG,甘油三酯;TC,总胆固醇;LDL,低密度脂蛋白;Cr,肌酐;BA,血氨;CD4+,CD4 T细胞计数;CD8+,CD8 T细胞计数;IL-6,白细胞介素6;TNF-α,肿瘤坏死因子α。

    下载: 导出CSV

    表  3  PHC患者并发心肌损伤的多因素Logistic回归分析

    Table  3.   Multivariate Logistic regression analysis of myocardial injury in patients with PHC

    参数 β值 SE Wald χ2 P值 OR(95%CI)
    年龄 0.050 0.007 46.500 <0.001 1.051(1.036~1.067)
    糖尿病史 0.621 0.165 14.134 <0.001 1.862(1.346~2.574)
    心电图 0.369 0.150 6.036 0.014 1.446(1.077~1.940)
    HGB -0.007 0.002 8.897 0.003 0.993(0.988~0.998)
    Alb -0.051 0.011 20.400 <0.001 0.951(0.930~0.972)
    Cr 0.021 0.003 63.270 <0.001 1.021(1.016~1.026)

    注:PHC,原发性肝癌;HGB,血红蛋白;Alb,白蛋白;Cr,肌酐;OR,比值比;CI,置信区间;SE,标准误。

    下载: 导出CSV
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