Pei J Y, Zhang D D, He H, Zheng L L, Du S Z, Jing Z W
Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Department of Traditional Chinese Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Zhonghua Xin Xue Guan Bing Za Zhi. 2023 Dec 24;51(12):1247-1255. doi: 10.3760/cma.j.cn112148-20231008-00254.
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. 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 (), and the receiver operating characteristic (ROC) analysis was evaluated for the risk prediction values of changed metabolites. 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%. 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.
通过鉴定血清中的不同代谢物,阐明代谢综合征(MS)和稳定型冠状动脉疾病患者潜在的代谢紊乱途径,以评估基于血清代谢组学的特定代谢物对超重或肥胖人群中MS和冠心病发生的预测价值。这是一项回顾性横断面研究。2017年至2019年从郑州大学第一附属医院中心院区招募的代谢综合征患者(MS组)、稳定型冠心病患者(冠心病组)和超重或肥胖个体(对照组)被纳入训练集,同时,将同期从该医院东区招募的相应三组人群纳入验证测试。血清代谢组学谱通过超高效液相色谱-四极杆/轨道阱高分辨率质谱(UHPLC-Q-Orbitrap HRMS)测定。还收集了临床特征(年龄、性别、体重指数(BMI)、血压、空腹血糖(FPG)、糖化血红蛋白(HbA1c)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、肾小球滤过率(eGFR)、肌酐(CR))。基于正交偏最小二乘判别分析(OPLS-DA)模型,根据投影变量重要性(VIP)筛选出MS和冠心病患者中显著变化的代谢物,并对变化代谢物的风险预测值进行受试者工作特征(ROC)分析。本研究共招募了488名受试者,训练集包括40名MS患者、249名冠心病患者和148名对照,验证集包括16名MS患者、18名冠心病患者和17名对照。我们对冠心病与对照、MS与对照以及冠心病与MS的血清代谢物进行了比较,共鉴定出22种不同的代谢物。涉及的紊乱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,我们鉴定出2种MS特异性代谢物(磷脂酰胆碱(18∶1(9Z)e/20)和哌啶酸)、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)以及4种MS和冠心病共有的代谢物(异亮氨酸、苯丙氨酸、谷胱甘肽和溶血磷脂酰胆碱(14∶0))。基于ROC曲线的截断值,上述代谢物对超重或肥胖人群中MS发生的预测价值为100%,对冠心病发生的预测价值为87.5%,对MS患者中冠心病的风险预测价值为82.1%。血清代谢物的改变表明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定代谢物对超重或肥胖人群中MS和冠心病的发生具有良好的预测价值。