Myocardial ischemia is a leading cause of cardiovascular morbidity and mortality; however, early and noninvasive diagnosis remains challenging. Conventional diagnostic methods, including electrocardiography, coronary angiography, and myocardial perfusion imaging have limitations in detecting early-stage ischemia. This study aimed to identify plasma metabolite biomarkers associated with early myocardial ischemia using liquid chromatography–quadrupole time-of-flight mass spectrometry (LC–QTOF/MS) based metabolomics. Eighty-nine patients with suspected myocardial ischemia hospitalized at Kyungpook National University Hospital were screened. After applying exclusion criteria, 43 patients were enrolled and divided into 2 groups: control (n = 24, no angiographic stenosis) and case (n = 19, >70% stenosis in vessels with a diameter of ≥2.5 mm). All participants underwent an exercise stress test based on the Bruce protocol. Plasma samples were collected before and 10 minutes after exercise. Untargeted LC–QTOF/MS profiling was performed, and multivariate analyses (principal component analysis and orthogonal partial least squares-discriminant analysis) were used to identify differential metabolites. Receiver operating characteristic analysis was conducted to evaluate diagnostic performance. Multivariate modeling revealed distinct metabolic differences between the groups. Thirteen metabolites were significantly altered in both groups, while 9 changed exclusively in the ischemia group following exercise. Notably, several phosphatidylcholine (PC) species – PC (O-18:5/2:0), PC (O-16:0/22:4), PC (O-18:4/18:2), and PC (20:4/20:4) – as well as 13Z-docosenamide, differed significantly between groups. Receiver operating characteristic analysis identified 3 key metabolites – 13Z-docosenamide, PC (16:0/22:5), and PC (18:1/20:4) – with excellent discriminative performance (area under the curve = 0.941; 95% confidence interval: 0.865–1.000; sensitivity, 92%; specificity, 93%). Pathway analysis indicated that exercise-induced ischemia was associated with alterations in phospholipid, sphingolipid, and fatty acid metabolism, reflecting hypoxia-mediated energy shifts and oxidative stress. LC–MS-based metabolomic profiling identified distinct lipid metabolic signatures associated with early myocardial ischemia. The metabolites 13Z-docosenamide, PC (16:0/22:5), and PC (18:1/20:4) demonstrated strong diagnostic potential and may serve as early biomarkers for the noninvasive detection of myocardial ischemia. Further validation in independent cohorts might be required to confirm their clinical applicability.
Han et al. (Fri,) studied this question.