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Coronary heart disease (CHD) is associated with complex metabolic disorders, but its molecular aetiology remains unclear. Using a novel nontargeted metabolomics approach, we explored the global metabolic perturbation profile for CHD. Blood samples from 150 patients with severe obstructive CHD and 150 angiographically normal controls were collected. Metabolic fingerprinting was performed by ultra-high performance liquid chromatography coupled to quadruple time-of-flight mass spectrometry (UHPLC-QTOF/MS) technique. After adjusting for CHD traditional risk factors and metabolic batch, a comprehensive list of 105 metabolites was found to be significantly altered in CHD patients. Among the metabolites identified, six metabolites were discovered to have the strongest correlation with CHD after adjusting for multiple testing: palmitic acid (β = 0.205; p < 0.0001), linoleic acid (β = 0.133; p < 0.0001), 4-pyridoxic acid (β = 0.142; p < 0.0001), phosphatidylglycerol (20:3/2:0) (β = 0.287; p < 0.0001), carnitine (14:1) (β = 0.332; p < 0.0001) and lithocholic acid (β = 0.224; p < 0.0001); of these, 4-pyridoxic acid, lithocholic acid and phosphatidylglycerol (20:3/2:0) were, to the best of our knowledge, first reported in this study. A logistic regression model further quantified their positive independent correlations with CHD. In conclusion, this study surveyed a broad panel of nontargeted metabolites in Chinese CHD populations and identified novel metabolites that are potentially involved in CHD pathogenesis.

Background: The potential impact of quantitative flow ratio (QFR) based functional Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) score (FSS QFR ) on prognostication and revascularization strategy choice has not been fully investigated, and the discriminant ability of FSS QFR needs further validation. Methods: QFR was retrospectively analyzed in left main or patients with multivessel coronary artery disease from the PANDA III trial. A total of 607 patients with analyzable QFR in all vessels were included. FSS QFR was counted by summing the individual scores only in ischemia-producing lesions (vessel QFR ≤0.8). Patients were stratified according to tertiles of SYNTAX score (SS), and 3 groups of FSS were divided by the same cutoff score. The primary end point was 2-year major adverse cardiac events (a composite of cardiac death, any myocardial infarction, or ischemia-driven revascularization). Results: After calculating the FSS QFR , 16% (96/607) of study patients moved from higher-risk group by SS to lower-risk group. In the low, intermediate, and high FSS QFR group, the cumulative incidence of 2-year major adverse cardiac events was 9.1%, 13.5%, and 22.3% ( P =0.0004), and the rate of a composite of cardiac death or myocardial infarction (3.8%, 7.3%, and 13.7%, P= 0.0006) was also increased. Compared with SS, FSS QFR significantly improved risk classification and prognostication (area under the curve of the receiver-operating characteristics 0.65 versus 0.62, P= 0.0009). Moreover, 6% (38/607) of patients, for whom coronary artery bypass grafting would be recommended according to SS, converted to favor percutaneous coronary intervention after FSS QFR calculation. After multivariate adjustment, FSS QFR was an independent predictor of 2-year major adverse cardiac events (adjusted hazard ratio, 1.05 [95% CI, 1.02–1.07]; P =0.0001). Conclusions: Among patients with left main or multivessel coronary artery disease, FSS QFR showed applicability in prognostication and revascularization strategy choice. An improved scoring system combining anatomy and physiology (FSS QFR ) discriminated the risk of adverse events modestly better than anatomic assessment (SS) alone. REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02017275.