Glycolysis Metabolites and Risk of Atrial Fibrillation and Heart Failure in the PREDIMED Trial.

Cristina Razquín ,Pablo Hernández‐Alonso ,Fernando Arós,Kerry A Pierce ,Jun Li,Jordi Salas‐Salvadó ,Miguel Ruiz‐Canela ,Mònica Bulló,Marta Guasch‐Ferré ,Lluís Serra‐Majem ,Clary B Clish,Liming Liang,Ramón Estruch ,Estefanía Toledo,Nerea Becerra‐Tomás ,Emilio Ros,Dolores Corella,Montserrat Fitó ,Enrique Gómez‐Gracia ,Chih‐Hao Lee ,Frank B Hu

doi:10.3390/metabo11050306

Abstract

The increased prevalence of atrial fibrillation (AF) and heart failure (HF) highlights the need to better understand the mechanisms underlying these cardiovascular diseases (CVDs). In the present study, we aimed to evaluate the association between glycolysis-related metabolites and the risk of AF and HF in a Mediterranean population at high risk of CVD. We used two case–control studies nested within the PREDIMED trial. A total of 512 incident AF cases matched to 734 controls, and 334 incident HF cases matched to 508 controls, were included. Plasma metabolites were quantified by using hydrophilic interaction liquid chromatography coupled with high-resolution negative ion mode MS detection. Conditional logistic regression analyses were performed. The results showed no association between baseline plasma glycolysis intermediates and other related metabolites with AF. Only phosphoglycerate was associated with a higher risk of HF (OR for 1 SD increase: 1.28; 95% CI: 1.06, 1.53). The present findings do not support a role of the glycolysis pathway in the pathogenesis of AF. However, the increased risk of HF associated with phosphoglycerate requires further studies.

Highlights

Heart failure (HF) and atrial fibrillation (AF)—the most common type of arrhythmia—have emerged as major cardiac public health problems
The results of the present analysis, which included two case–control studies nested within the PREDIMED trial, showed no association between plasma glycolysis and related metabolites and AF risk
Previous studies have reported glucose oxidation impairment and increased glycolysis activity in patients with heart failure (HF), which is reflected by higher levels of pyruvate and/or lactate compared to healthy controls [8,12,13,14]

Summary

Introduction

Heart failure (HF) and atrial fibrillation (AF)—the most common type of arrhythmia—have emerged as major cardiac public health problems. The traditional risk factors do not completely explain all AF and HF cases, and a deeper knowledge of the pathophysiology of HF and AF is needed [4,5]. In this sense, metabolomics could enhance our understanding of their pathogenic pathways, and help develop preventive strategies through the identification of novel risk biomarkers for these complex diseases. In patients with AF and HF, perturbations of the glycolysis metabolism have been detected [6,7] It is still debated whether altered glycolysis metabolism happens and is implicated before the development of AF and HF, or whether it is a consequence of these diseases [8]

Objectives

Methods

Conclusion