Prognostic circulatory signature metabolites of stable versus unstable angina: an application of NMR spectroscopy.

Abstract

In spite of the ongoing efforts to probe the metabolic signatures of stable (SA) from unstable (UA) angina, it is concerning that to date there are no clinically validated circulatory biochemical signatures against the intrinsic anatomical changes that are screened by invasive coronary angiography. Hence, the aim of this study is to generate precise biochemical fingerprints using filtered serum-based metabolomics and high-throughput nuclear magnetic resonance (NMR) spectroscopy to accurately distinguish the metabolic signatures of patients suffering with SA or UA angina. The study includes 118 filtered serum samples from patients suffering from UA (n = 50) and SA (n = 68). High-resolution NMR spectroscopy was used to assess the metabolic remodeling in these cohorts. Subsequently, principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA), and artificial neural network (ANN) analysis were adapted to engender a precise prediction model. Analysis of the receiver operating characteristic (ROC) curve was conducted to determine the clinical usefulness of metabolic markers. The outcome revealed that the metabolic profile for the underlying disease is characterized by altered metabolite levels in UA relative to SA. Creatinine, 3-OH butyrate, and aspartate level could differentiate 100% of UA from SA with 100% sensitivity and specificity. To monitor and determine UA from patients with SA, ¹H NMR-based filtered serum metabolic profiling seems to be a promising, less invasive, and faster investigative approach.NEW & NOTEWORTHY There are no metabolic signatures present to identify unstable from stable angina. Coronary angiography identifies anatomical changes after the event of unstable angina, but NMR-based metabolomics identifies unstable from stable angina within 4 h. Creatinine, 3-OH butyrate, and aspartate were able to segregate unstable from stable angina.