Plasma Metabolic Profiling Analysis of Heart Failure with Preserved Ejection Fraction Patients Based on UHPLC-MS/MS

Background Heart failure with preserved ejection fraction (HFpEF) is a complex disease characterized by metabolic disturbances that can have various pathophysiological implications. Methods Data were collected from a prospective cohort consisting of 30 HFpEF participants and 30 healthy controls, matched by gender and age. untargeted metabolomic profiling UHPLC-MS/MS was performed on Venous blood. The analyses aimed to reveal the differences in plasma metabolic characteristics between HFpEF participants and healthy controls using untargeted metabolomics. Initial steps included Principal Components Analysis (PCA), Partial Least Squares-Discriminant Analysis (PLS-DA), and hierarchical clustering analysis to detect differing compounds groups. Subsequently, Receiver Operating Characteristic (ROC) curve analysis and pathway analysis of the different metabolites. Finally, we performed pathway enrichment analysis to identify significantly dysregulated processes. Results A total of 124 significantly different compounds were selected based on criteria of Variable Importance in Projection (VIP) > 1.0, Fold Change (FC) > 1.2 or FC < 0.833, and P-value < 0.05. Compared to healthy control group, the most altered metabolites in HFpEF were lipids and lipid-like molecules. KEGG enrichment and pathway impact analysis highlight the enrichment of these differentially expressed metabolites primarily in tryptophan metabolism. Hierarchical clustering results, showed varying compound levels between the two groups. ROC curve results, revealed Cytosine and 1,2-dihydroxyheptadec-16-yn-4-yl having higher AUC values. Conclusions Significant differences were observed in plasma metabolic profiles between HFpEF patients and healthy subjects using UHPLC-MS/MS. Cytosine appeared a potential biomarker. Tryptophan metabolism may be a novel metabolic pathway of HFpEF.