急性冠状动脉综合征患者主要不良心血管事件的预测模型构建及验证

Construction and validation of predictive models for major adverse cardiovascular events in patients with acute coronary syndrome

  • 摘要:
    目的 基于心率变异性(HRV)建立列线图模型,并评估急性冠状动脉综合征(ACS)患者主要不良心血管事件(MACEs)的发生风险。
    方法 回顾性纳入确诊ACS患者322例作为建模集,另选择164例ACS患者作为验证集,中位随访时间为23.5个月。将建模集分为MACEs组30例和无MACEs组292例,分别采用单因素分析与多因素Cox回归分析筛选危险因素,并建立列线图模型。采用受试者工作特征(ROC)曲线、校准曲线与决策曲线验证模型,以及采用Kaplan-Meier生存曲线进行风险分层。
    结果 建模集与验证集的性别、年龄、ACS类型、靶血管直径狭窄率、支架置入、MACEs发生率等一般资料比较,差异有统计学意义(P < 0.05)。单因素分析发现, MACEs组年龄大于无MACEs组, ST段抬高型心肌梗死(STEMI)和既往心肌梗死病史例数占比及入院肌酸激酶同工酶(CK-MB)、肌钙蛋白I(cTnI)、B型利钠肽(BNP)和靶血管直径狭窄率、标准化高频(HF)值高于无MACEs组, HRV指标中标准化低频(LF)值、标准化LF/HF低于无MACEs组,差异有统计学意义(P < 0.05)。多因素Cox回归分析显示,年龄≥65岁(HR=1.425, 95%CI: 1.124~1.758, P=0.001)、既往心肌梗死病史(HR=1.326, 95%CI: 1.102~1.659, P=0.003)和标准化LF/HF < 1.32(HR=2.203, 95%CI: 1.568~2.659, P < 0.001)是ACS患者随访2年MACEs的独立危险因素。R软件建立列线图模型,总分200分。ROC曲线显示,列线图模型预测建模集1年与2年MACEs的曲线下面积(AUC)分别为0.845和0.902, 预测验证集1年与2年MACEs的AUC分别为0.802和0.856。校准曲线与决策曲线均显示,模型有较好的吻合度和净获益比。Kaplan-Meier生存曲线显示,建模集与验证集1年和2年高风险(>80分)累积MACEs发生率大于中风险(60~80分)、低风险(< 60分),其中低风险最低(P < 0.05)。
    结论 ACS患者入院早期检测HRV有利于准确评估介入干预后中长期随访MACEs的发生风险。ACS患者年龄、既往心肌梗死病史联合标准化LF/HF建立的列线图模型在评估预后风险分层中具有重要应用潜力。

     

    Abstract:
    Objective To establish a nomograph model based on heart rate variability (HRV) and evaluate the risk of major adverse cardiovascular events (MACEs) in patients with acute coronary syndrome (ACS).
    Methods A total of 322 patients with confirmed ACS were retrospectively included as the modeling set, and 164 patients with ACS were selected as the validation set. The median follow-up time was 23.5 months. The modeling set was divided into MACEs group(n=30) and non-MACEs group(n=292). The risk factors were screened by single-factor comparison and multi-factor Cox regression analysis respectively, and the nomogram model was established. Receiver operator characteristic (ROC) curve, calibration curve and decision curve were used to verify the model, and Kaplan-Meier survival curve was used for risk stratification.
    Results There were statistically significant differences in gender, age, ACS type, target vessel diameter stenosis rate, stent placement and incidence of MACEs between the modeling set and the validation set (P < 0.05). Univariate comparison showed that the age of the MACEs group was significantly higher, the proportion of ST-segment elevation myocardial infarction (STEMI) and history of myocardial infarction, admission creatine kinase isoenzyme (CK-MB), troponin I (cTnI) and B-type natriuretic peptide (BNP), target vessel diameter stenosis rate and standardized high frequency (HF) value were significantly higher, the standardized low frequency (LF) value in HRV index and the standardized LF/HF were significantly lower than those in the non-MACEs group (P < 0.05). Multivariate Cox regression analysis showed that age ≥65 years (HR=1.425; 95%CI, 1.124 to 1.758; P=0.001) and previous history of myocardial infarction (HR=1.326; 95%CI, 1.102 to 1.659; P=0.003) and standardized LF/HF < 1.32 (HR=2.203; 95%CI, 1.568 to 2.659; P < 0.001) were independent risk factors for MACEs in ACS patients followed up for two years. R software was used to establish a nomogram model, with a total score of 200 points. ROC showed that the area under the curve (AUC) of the 1-year and 2-year MACEs predicted by the nomogram model was 0.845 and 0.902, respectively, and the AUC of 1-year and 2-year MACEs for the prediction validation set was 0.802 and 0.856, respectively. Both the calibration curve and the decision curve showed that the model had good consistency and net benefit ratio. Kaplan-Meier survival curve showed that the cumulative incidence of MACEs at 1-year and 2-year high-risk (≥80 points) in modeling set and validation set was higher than that at medium-risk (60 to 80 points) and low-risk (< 60 points), and low-risk was the lowest (P < 0.05).
    Conclusion Early detection of HRV in ACS patients is beneficial to accurately assess the risk of MACEs in the medium- and long-term follow-up after intervention. The age of ACS patients, past history of MI combined with standardized LF/HF map model has important application potential in assessing prognostic risk stratification.

     

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