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
Risk factors for concurrent myocardial injury before intervention in patients with primary hepatic carcinoma and construction of a nomogram prediction model
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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。 Abstract:Objective To investigate the independent risk factors for concurrent myocardial injury before intervention in patients with primary hepatic carcinoma (PHC), to construct and validate a nomogram prediction model for the early identification of such patients, and to provide a basis for early clinical prevention and management. Methods A retrospective analysis was performed for the clinical data of 1 822 patients with PHC in two medical institutions from January 2019 to June 2025, among whom the 1 518 patients from The Third People’s Hospital of Kunming were used as the training set to construct the nomogram prediction model, and the 304 patients from The Second People’s Hospital of Baoshan were used as the validation set. According to the result of high-sensitivity cardiac troponin T measurement before intervention, the patients with PHC were divided into myocardial injury group and non-myocardial injury group. The univariate analysis, the LASSO regression analysis, and the multivariate Logistic regression analysis were used to identify the risk factors of concurrent myocardial injury in PHC patients before intervention, and then a nomogram prediction model was constructed based on these findings. The independent data of the 304 patients in the validation set were used for external validation, and the area under the receiver operating characteristic curve (AUC), the Hosmer-Lemeshow test, the calibration curve, decision curve analysis, and clinical impact curve were used to assess model performance. Results In the training set, there were 346 patients in the myocardial injury group and 1 172 patients in the non-myocardial injury group, and the prevalence rate of concurrent myocardial injury was 22.79%. The mean age was 56.44±9.45 years, and the male patients accounted for 81.49%. The patients with drinking, smoking, chronic hepatitis B, chronic hepatitis C, hypertension, diabetes, Child-Pugh class A liver disease, BCLC stage B liver disease, or abnormal electrocardiographic findings accounted for 49.34%, 57.44%, 61.73%, 32.48%, 22.66%, 17.19%, 50.53%, 33.86%, and 62.12%, respectively. The univariate analysis, the LASSO regression analysis, and the multivariate Logistic regression analysis showed that age (odds ratio [OR]=1.051, 95% confidence interval [CI]: 1.036 — 1.067, P<0.001), history of diabetes (OR=1.862, 95%CI: 1.346 — 2.574, P<0.001), electrocardiographic findings (OR=1.446, 95%CI: 1.077 — 1.940, P=0.014), hemoglobin (HGB) (OR=0.993, 95%CI: 0.988 — 0.998, P=0.003), albumin (Alb) (OR=0.951, 95%CI: 0.930 — 0.972, P<0.001), and creatinine (Cr) (OR=1.021, 95%CI: 1.016 — 1.026, P<0.001) were independent influencing factors for myocardial injury in PHC patients. A regression equation was established as Logit(Y)=-3.406+0.050×age+0.621×history of diabetes+0.369×electrocardiogram-0.007×HGB-0.051×Alb+0.021×Cr, and a nomogram prediction model was constructed based on these factors. The Bootstrap internal validation of the model yielded an AUC of 0.743 (95%CI: 0.707 — 0.778), and the model had an AUC of 0.766 (95%CI: 0.738 — 0.794) in the training set and 0.730 (95%CI: 0.688 — 0.793) in the validation set. The Hosmer-Lemeshow goodness-of-fit test yielded a P value of 0.716 for the training set and 0.408 for the validation set, suggesting that the model had a good degree of fitting. Calibration curves, decision curve analysis, and clinical impact curves in both the training set and the validation set showed that the model had a good clinical application value. Conclusion Age, history of diabetes, electrocardiographic findings, HGB, Alb, and Cr are independent influencing factors for myocardial injury in patients with PHC, and the nomogram prediction model constructed based on these factors has good discriminatory ability, accuracy, and clinical practicability. -
Key words:
- Liver Neoplasms /
- Myocardial Injury /
- Risk Factors /
- Nomogram
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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。
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。
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。
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