Zhong Zhixiong, Liu Jing, Zhang Qifeng, Zhong Wei, Li Bin, Li Cunren, Liu Zhidong, Yang Min, Zhao Pingsen
Center for Cardiovascular Diseases, Meizhou People's Hospital (Huangtang Hospital), Meizhou Academy of Medical Sciences, Meizhou Hospital Affiliated to Sun Yat-sen University.
Guangdong Provincial Engineering and Technology Research Center for Molecular Diagnostics of Cardiovascular Diseases.
Medicine (Baltimore). 2019 Feb;98(7):e14309. doi: 10.1097/MD.0000000000014309.
Coronary heart disease (CHD), one of the leading causes of death in the world, is a complex metabolic disorder due to genetic and environmental interactions. The potential mechanisms and diagnostic biomarkers for different types of coronary heart disease remain unclear. Metabolomics is increasingly considered to be a promising technology with the potential to identify metabolomic features in an attempt to distinguish the different stages of CHD.We aimed to investigate serum metabolite profiling between CHD patients and normal coronary artery (NCA) subjects and identify metabolic biomarkers associated with CHD progression in an ethnic Hakka population in southern China.Using a novel targeted metabolomics approach, we explored the metabolic characteristics of CHD patients. Blood samples from 302 patients with CHD and 59 NCA subjects were collected that analyses using targeted liquid-chromatography coupled with tandem mass spectrometry (LC-MS).A total of 361 blood samples were determined using targeted LC-MS. Plasma concentrations for trimetlylamine oxide (TMAO), choline, creatinine, and carnitine were significantly higher in patients with CHD compared to the NCA cohort. Further, we observed that the concentration of the 4 metabolites were higher than that of the NCA group in any group of CHD, which including acute myocardial infarction (AMI), unstable angina (UA), and stable angina (SA). In addition, the diagnostic model was constructed based on the metabolites identified and the ROC curve of the NCA subjects and CHD patients were performed. For choline and creatinine, the AUCs ranged from 0.720 to 0.733. For TMAO and carnitine, the AUCs ranged from 0.568 to 0.600.In conclusion, the current study illustrates the distribution of 4 metabolites between CHD patients and NCA subjects. Metabolomics analysis may yield novel predictive biomarkers that will potentially provide value for clinical diagnosis of CHD.
冠心病（CHD）是全球主要死因之一，是一种由遗传和环境相互作用导致的复杂代谢紊乱疾病。不同类型冠心病的潜在机制和诊断生物标志物仍不明确。代谢组学越来越被认为是一项有前景的技术，有潜力识别代谢组特征以区分冠心病的不同阶段。我们旨在研究中国南方客家人群中冠心病患者与正常冠状动脉（NCA）受试者之间的血清代谢物谱，并识别与冠心病进展相关的代谢生物标志物。使用一种新型靶向代谢组学方法，我们探索了冠心病患者的代谢特征。收集了302例冠心病患者和59例NCA受试者的血样，采用靶向液相色谱-串联质谱（LC-MS）进行分析。共对361份血样进行了靶向LC-MS测定。与NCA队列相比，冠心病患者的氧化三甲胺（TMAO）、胆碱、肌酐和肉碱的血浆浓度显著更高。此外，我们观察到在任何一组冠心病中，这4种代谢物的浓度均高于NCA组，其中包括急性心肌梗死（AMI）、不稳定型心绞痛（UA）和稳定型心绞痛（SA）。此外，基于所鉴定的代谢物构建了诊断模型，并对NCA受试者和冠心病患者进行了ROC曲线分析。对于胆碱和肌酐，AUC范围为0.720至0.733。对于TMAO和肉碱，AUC范围为0.568至0.600。总之，本研究阐明了冠心病患者与NCA受试者之间4种代谢物的分布情况。代谢组学分析可能会产生新的预测生物标志物，这可能为冠心病的临床诊断提供价值。
