Glycolysis metabolites and risk of atrial fibrillation and heart failure in the PREDIMED trial

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.This research was funded by The National Institutes of Health (R01HL118264), the Spanish Ministry of Health (Instituto de Salud Carlos III), and the Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional (Projects CNIC-06/2007, RTIC G03/140, CIBER 06/03, PI06-1326, PI07-0954, PI11/02505, SAF2016-80532, SAF2009-12304 and AGL2010-22319-C03-03), and by the Generalitat Valenciana (PROMETEO 17/2017, ACOMP2010-181, AP111/10, AP-042/11, ACOM2011/145, ACOMP/2012/190, ACOMP/2013/159 and ACOMP/213/165), and CIBER Obesidad y Nutrición, Madrid, Spain, Fondo de Investigación Sanitaria, Madrid, Spain. THEMATIC NETWORK “PREDIMED”, RD 06/0045, coordinated by MAM-G, funded by ISCIII 2006-2013. N. Becerra-Tomás, a postdoctoral fellowship (Juan de la Cierva Formación, FJC2018-036016-I); P. Hernández-Alonso, a postdoctoral fellowship (Juan de la Cierva Formación, FJCI-2017-32205); M. Guasch-Ferré, American Diabetes Association grant #1-18-PMF-029; E. Ros, grants for research through his institution from the California Walnut Commission (CWC); J. Salas-Salvadó (senior author of this work), partially supported by ICREA under the ICREA Academia programme, grants/research support from the American Pistachio Growers and International Nut and Dried Fruit Foundation through his Institution