EV-derived pyruvate and lactic dehydrogenase B levels were significantly elevated in sudden cardiac death patients compared to controls, enhancing SCD risk prediction (AUC 0.9).
Do plasma extracellular vesicle-derived pyruvate and LDHB levels predict sudden cardiac death risk in patients with acute coronary syndrome?
Plasma extracellular vesicle-derived pyruvate and LDHB are promising novel biomarkers that, especially when combined with traditional markers like creatine kinase isoenzyme, significantly enhance the prediction of sudden cardiac death risk in patients with acute coronary syndrome.
Absolute Event Rate: 0% vs 0%
Objectives: The identification of early warning biomarkers and associated molecular mechanisms of sudden cardiac death (SCD) caused by acute coronary syndrome (ACS) through the analysis of peripheral blood plasma extracellular vehicles (EVs) remains a significant gap in current knowledge. We aimed to screen for novel EV metabolic markers and validate their prediction ability thereby providing novel early diagnostic biomarkers for the risk of sudden death due to ACS; based on the premise that EVs mirror cellular metabolic stress, we hypothesized that specific EV metabolic signatures can predict SCD risk in ACS patients.. Methods: In this nested case-control study, plasma EVs from 18 non-ST-segment elevation ACS (NSTE-ACS), 21 ST-segment elevation myocardial infarction, 16 ACS-related SCD patients and 41 matched controls were isolated and characterized in accordance with the Minimal Information for Studies of Extracellular Vesicles 2018 guidelines. We performed a combined liquid chromatography-tandem mass spectrometry-based metabolomic and proteomic analysis of plasma EVs, conducted multi-omics integration for pathway and network analysis, and validated candidate biomarkers by enzyme-linked immunosorbent assay. ROC curve analysis and multivariate/univariate statistical methods were applied to evaluate the SCD risk predictive value of the identified markers. Results: We identified 27 differential metabolites associated with the progression of SCD in plasma EVs of ACS patients. The combined analysis suggested that glycolysis and the tricarboxylic acid cycle might be key metabolic pathways in SCD. Notably, EV-derived pyruvate and lactic dehydrogenase B (LDHB) levels were significantly elevated in SCD patients compared to controls ( P <0.05), despite no differences in plasma concentrations, suggesting EV-derived pyruvate and LDHB as early biomarker to predict SCD in ACS patients. Integration of EV-derived pyruvate and LDHB with traditional biomarkers (creatine kinase isoenzyme, myoglobin MYO) improved SCD risk prediction (area under the curve AUC 0.786 for pyruvate + LDHB; AUC 0.9 when combined with creatine kinase isoenzyme), underscoring their potential for enhancing risk stratification. Conclusion: In this nested case-control study of ACS patients, multi-omics profiling of plasma EVs revealed altered distinct metabolic signatures in SCD cases, particularly the LDHB-pyruvate-spermine-spermidine network involoved in glycolysis and the tricarboxylic acid cycle. LDHB and pyruvate emerged as co-diagnostic biomarkers, enhancing predictive accuracy for cardiovascular events when combined with clinical indicators.
Wan et al. (Tue,) reported a other. EV-derived pyruvate and lactic dehydrogenase B levels were significantly elevated in sudden cardiac death patients compared to controls, enhancing SCD risk prediction (AUC 0.9).