[Risk prediction of metabolic syndrome and coronary artery disease in overweight and obese populations based on serum metabolomics].

Objective: By identifying different metabolites in the serum and clarifying the potential metabolic disorder pathways in metabolic syndrome (MS) and stable coronary artery disease patients, to evaluate the predictive value of specific metabolites based on serum metabolomics for the occurrence of MS and coronary heart disease in overweight or obese populations. Methods: This is a retrospective cross-sectional study. Patients with Metabolic Syndrome (MS group), patients with stable coronary heart disease (coronary heart disease group), and overweight or obese individuals (control group) recruited from the Central District of the First Affiliated Hospital of Zhengzhou University from 2017 to 2019 were assigned to the training set, meanwhile, the corresponding three groups of people recruited from the East District of the hospital during the same period were assigned to the validation test. The serum metabolomics profiles were determined by ultra-performance liquid chromatography-quadrupole/orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). Clinical characteristics (age, gender, body mass index (BMI), blood pressure, fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), alanine aminotransferase (ALT), aspartate transaminase (AST), total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), glomerular filtration rate (eGFR), creatinine (CR)) were also collected. Based on the orthogonal partial least-squares discrimination analysis (OPLS-DA) model, the significantly changed metabolites for MS and coronary artery disease patients were screened according to variable important in projection (VIP), and the receiver operating characteristic (ROC) analysis was evaluated for the risk prediction values of changed metabolites. Results: A total of 488 subjects were recruited in this study, the training set included 40 MS, 249 coronary artery disease patients and 148 controls, the validation set included 16 MS, 18 coronary artery disease patients and 17 controls. We made comparisons of the serum metabolites of coronary artery disease vs. controls, MS vs. controls, and coronary artery disease vs. MS, and a total of 22 different metabolites were identified. The disturbed metabolic pathways involved were phospholipid metabolism, amino acid metabolism, purine metabolism and other pathways. Through cross-comparisons, we identified 2 specific metabolites for MS (phosphatidylcholine (18∶1(9Z)e/20) and pipecolic acid), 4 specific metabolites for coronary artery disease (lysophosphatidylcholine (17∶0), PC(16∶0/16∶0), hypoxanthine and histidine), and 4 common metabolites both for MS and coronary artery disease (isoleucine, phenylalanine, glutathione and LysoPC(14∶0)). Based on the cut-off values from ROC curve, the predictive value of the above metabolites for the occurrence of MS in overweight or obese populations is 100%, the predictive value for the occurrence of coronary heart disease is 87.5%, and the risk predictive value for coronary heart disease in MS patients is 82.1%. Conclusions: The altered serum metabolites suggest that MS and coronary heart disease may involve multiple metabolic pathway disorders. Specific metabolites based on serum metabolomics have good predictive value for the occurrence of MS and coronary heart disease in overweight or obese populations.目的： 鉴定受试者血清中的不同代谢物，以明确代谢综合征（MS）和稳定型冠心病患者的潜在代谢紊乱途径，评估基于血清代谢组学的特异性代谢物群对超重或肥胖人群发生MS和冠心病的预测价值。 方法： 本研究为回顾性横断面研究。以2017—2019年郑州大学第一附属医院河医院区招募的MS患者（MS组）、稳定型冠心病患者（冠心病组）和超重或肥胖者（对照组）作为训练集，以同时期该医院郑东院区招募的对应3组人群作为验证集。采用超高效液相色谱-四级杆/静电场轨道阱高分辨率质谱分析受试者的血清代谢组学特征，收集相关的临床资料，包括年龄、性别、体重、身高、血压、空腹血糖（FPG）、糖化血红蛋白（HbA1c）、谷丙转氨酶（ALT）、谷草转氨酶（AST）、血脂、估算的肾小球滤过率（eGFR）、肌酐清除率（CR）等。在正交偏最小二乘判别分析模型（OPLS-DA）基础上，根据变量权重（VIP）筛选MS和冠心病患者显著改变的代谢物。绘制受试者工作特征曲线（ROC）并做风险预测。 结果： 本研究共纳入488例研究对象，其中训练集MS组40例、冠心病组249例、对照组148例；验证集MS组16例、冠心病组18例、对照组17例。分别比较冠心病组和对照组、MS组和对照组、冠心病组和MS组的血清样本代谢物，共鉴定出22种差异代谢物。改变的代谢途径有磷脂代谢、氨基酸代谢、嘌呤代谢等途径。通过交叉比较，得到2种MS的特异性代谢物［磷脂酰胆碱（18∶1（9Z）e/2∶0）和哌唑酸］、4种冠心病特异性代谢物［溶血磷脂酰胆碱（17∶0）、PC（16∶0/16∶0）、次黄嘌呤和组氨酸］和4种MS和冠心病共有代谢物［异亮氨酸、苯丙氨酸、谷胱甘肽和溶血磷脂酰胆碱（14∶0）］。受试者工作特征曲线结果显示，血清代谢物对超重或肥胖人群发生MS的预测值为100%，发生冠心病的预测值为87.5%，对MS患者发生冠心病的风险预测值为82.1%。 结论： 血清代谢物的变化提示MS和冠心病可能涉及多种代谢途径紊乱。基于血清代谢组学的特异性代谢物群对超重或肥胖人群发生MS和冠心病具有良好的预测价值。.