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预测ST段抬高型心肌梗死患者院内结局的临床参数和代谢组学生物标志物

Clinical Parameters and Metabolomic Biomarkers That Predict Inhospital Outcomes in Patients With ST-Segment Elevated Myocardial Infarctions.

作者信息

Liu Jie, Huang Lei, Shi Xinrong, Gu Chungang, Xu Hongmin, Liu Shuye

机构信息

Clinical Laboratory Department, The Third Central Hospital of Tianjin, Tianjin, China.

Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China.

出版信息

Front Physiol. 2022 Feb 8;12:820240. doi: 10.3389/fphys.2021.820240. eCollection 2021.

Abstract

BACKGROUND

Postoperative risk stratification is challenging in patients with ST-segment elevation myocardial infarction (STEMI) who undergo percutaneous coronary intervention. This study aimed to characterize the metabolic fingerprints of patients with STEMI with different inhospital outcomes in the early stage of morbidity and to integrate the clinical baseline characteristics to develop a prognostic prediction model.

METHODS

Plasma samples were collected retrospectively from two propensity score-matched STEMI cohorts from May 6, 2020 to April 20, 2021. Cohort 1 consisted of 48 survivors and 48 non-survivors. Cohort 2 included 48 patients with unstable angina pectoris, 48 patients with STEMI, and 48 age- and sex-matched healthy controls. Metabolic profiling was generated based on ultra-performance liquid chromatography and a mass spectrometry platform. The comprehensive metabolomic data analysis was performed using MetaboAnalyst version 5.0. The hub metabolite biomarkers integrated into the model were tested using multivariate linear support vector machine (SVM) algorithms and a generalized estimating equation (GEE) model. Their predictive capabilities were evaluated using areas under the curve (AUCs) of receiver operating characteristic curves.

RESULTS

Metabonomic analysis from the two cohorts showed that patients with STEMI with different outcomes had significantly different clusters. Seven differentially expressed metabolites were identified as potential candidates for predicting inhospital outcomes based on the two cohorts, and their joint discriminative capabilities were robust using SVM (AUC = 0.998, 95% CI 0.983-1) and the univariate GEE model (AUC = 0.981, 95% CI 0.969-0.994). After integrating another six clinical variants, the predictive performance of the updated model improved further (AUC = 0.99, 95% CI 0.981-0.998).

CONCLUSION

A survival prediction model integrating seven metabolites from non-targeted metabonomics and six clinical indicators may generate a powerful early survival prediction model for patients with STEMI. The validation of internal and external cohorts is required.

摘要

背景

对于接受经皮冠状动脉介入治疗的ST段抬高型心肌梗死(STEMI)患者,术后风险分层具有挑战性。本研究旨在描绘发病早期不同院内结局的STEMI患者的代谢指纹图谱,并整合临床基线特征以建立预后预测模型。

方法

回顾性收集2020年5月6日至2021年4月20日两个倾向评分匹配的STEMI队列的血浆样本。队列1由48名幸存者和48名非幸存者组成。队列2包括48例不稳定型心绞痛患者、48例STEMI患者以及48名年龄和性别匹配的健康对照。基于超高效液相色谱和质谱平台进行代谢谱分析。使用MetaboAnalyst 5.0版本进行综合代谢组数据分析。使用多变量线性支持向量机(SVM)算法和广义估计方程(GEE)模型对纳入模型的核心代谢物生物标志物进行测试。使用受试者工作特征曲线的曲线下面积(AUC)评估其预测能力。

结果

两个队列的代谢组学分析表明,不同结局的STEMI患者具有明显不同的聚类。基于这两个队列,七种差异表达的代谢物被确定为预测院内结局的潜在候选物,使用SVM(AUC = 0.998,95% CI 0.983 - 1)和单变量GEE模型(AUC = 0.981,95% CI 0.969 - 0.994)时,它们的联合判别能力很强。纳入另外六个临床变量后,更新模型的预测性能进一步提高(AUC = 0.99,95% CI 0.981 - 0.998)。

结论

整合来自非靶向代谢组学的七种代谢物和六个临床指标的生存预测模型可能为STEMI患者生成一个强大的早期生存预测模型。需要对内部和外部队列进行验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4822/8862746/87cebb28bda8/fphys-12-820240-g001.jpg

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