title: Metabolomic profile for the early detection of coronary artery disease by using UPLC-QTOF/MS.
abstract: Traditional risk factors cannot promote prediction capacity for the patients with coronary artery disease (CAD), who usually do not show apparent symptoms until they develop acute myocardial infarction (AMI). As such, novel predictive diagnostic strategies are essential to accurately define patients at risk of acute coronary syndrome. In this study, non-targeted metabolomic profiling using ultra-performance liquid chromatography coupled to time of flight mass spectrometry (UPLC-QTOF/MS) was performed in combination with multivariate statistical model to analyze the serum samples of patients with stable angina (n=38), acute myocardial infarction (AMI) (n=34) and healthy age- and gender-matched controls (n=71). Results showed a clear distinction in metabolomic profiles between stable angina and AMI when using OPLS-DA with both positive and negative models. Internal cross-validation methods were used to confirm model validity with an area under the curve (AUROC)=0.983. We identified various classes of altered metabolites including phospholipids, fatty acids, sphingolipids, glycerolipids and steroids. We then demonstrated the differential roles of these metabolites using multivariate statistical model. Phospholipids previously associated with CAD were shown to have lower predictive capacity to discriminate AMI patients from stable angina patients. Interestingly, ceramides, bile acid and steroids hormone such as Cer(t18:0/16:0), Cer(d18:0/12:0), dehydroepiandrosterone sulfate (VIP scores of 1.99, 1.97, 1.64, respectively), were found to be associated with the progression of CAD. These results suggest that metabolomic approaches may facilitate the development of more stringent and predictive patient criteria in the diagnosis and treatment of CAD.
authors.affiliation: College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou 310027, China.
authors.forename: Xiaobao
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Hangzhou First People's Hospital, Hangzhou 310006, China; Affiliated Hangzhou Hospital, Nanjing Medical University, Hangzhou 310006, China.
authors.forename: Beibei
authors.initials: B
authors.lastname: Gao
authors.affiliation: College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou 310027, China.
authors.forename: Qijie
authors.initials: Q
authors.lastname: Guan
authors.affiliation: College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou 310027, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Hangzhou First People's Hospital, Hangzhou 310006, China; Affiliated Hangzhou Hospital, Nanjing Medical University, Hangzhou 310006, China.
authors.forename: Xianhua
authors.initials: X
authors.lastname: Ye
authors.affiliation: Department of Cardiology, Hangzhou First People's Hospital, Hangzhou 310006, China; Affiliated Hangzhou Hospital, Nanjing Medical University, Hangzhou 310006, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, Hangzhou First People's Hospital, Hangzhou 310006, China; Affiliated Hangzhou Hospital, Nanjing Medical University, Hangzhou 310006, China.
authors.forename: Guoxin
authors.initials: G
authors.lastname: Tong
authors.affiliation: Department of Cardiology, Hangzhou First People's Hospital, Hangzhou 310006, China; Affiliated Hangzhou Hospital, Nanjing Medical University, Hangzhou 310006, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou 310027, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou 310027, China. Electronic address: tjk@zju.edu.cn.
authors.forename: Jingkui
authors.initials: J
authors.lastname: Tian
authors.affiliation: Department of Cardiology, Hangzhou First People's Hospital, Hangzhou 310006, China; Affiliated Hangzhou Hospital, Nanjing Medical University, Hangzhou 310006, China. Electronic address: jinyuhuang0911@163.com.
authors.forename: Jinyu
authors.initials: J
authors.lastname: Huang
mesh_terms: D000368:Aged; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000175:diagnosis* / Q000378:metabolism*; D042241:Early Diagnosis; D006801:Humans; D008297:Male; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D053719:Tandem Mass Spectrometry / Q000379:methods*
keywords: Acute myocardial infarction; Coronary artery disease; Human serum; Metabolomics; Stable angina; UPLC-QTOF/MS