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oai:repisalud.isciii.es:20.500.12105/236142024-11-28T17:49:18Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16961col_20.500.12105_16967col_20.500.12105_16968col_20.500.12105_16983

00925njm 22002777a 4500 dc Santos, José L author Ruiz-Canela, Miguel author Razquin, Cristina author Clish, Clary B author Guasch-Ferré, Marta author Babio, Nancy author Corella, Dolores author Gómez-Gracia, Enrique author Fiol Sala, Miquel author Estruch, Ramon author Lapetra, José author Fito, Montserrat author Aros, Fernando author Serra-Majem, Lluis author Liang, Liming author Martínez, María Ángeles author Toledo, Estefanía author Salas-Salvado, Jordi author Hu, Frank B author Martínez-González, Miguel A author 2023-04 Background and aim: Plasma citric acid cycle (CAC) metabolites might be likely related to cardiovascular disease (CVD). However, studies assessing the longitudinal associations between circulating CAC-related metabolites and CVD risk are lacking. The aim of this study was to evaluate the association of baseline and 1-year levels of plasma CAC-related metabolites with CVD incidence (a composite of myocardial infarction, stroke or cardiovascular death), and their interaction with Mediterranean diet interventions. Methods and results: Case-cohort study from the PREDIMED trial involving participants aged 55-80 years at high cardiovascular risk, allocated to MedDiets or control diet. A subcohort of 791 participants was selected at baseline, and a total of 231 cases were identified after a median follow-up of 4.8 years. Nine plasma CAC-related metabolites (pyruvate, lactate, citrate, aconitate, isocitrate, 2-hydroxyglutarate, fumarate, malate and succinate) were measured using liquid chromatography-tandem mass spectrometry. Weighted Cox multiple regression was used to calculate hazard ratios (HRs). Baseline fasting plasma levels of 3 metabolites were associated with higher CVD risk, with HRs (for each standard deviation, 1-SD) of 1.46 (95%CI:1.20-1.78) for 2-hydroxyglutarate, 1.33 (95%CI:1.12-1.58) for fumarate and 1.47 (95%CI:1.21-1.78) for malate (p of linear trend <0.001 for all). A higher risk of CVD was also found for a 1-SD increment of a combined score of these 3 metabolites (HR = 1.60; 95%CI: 1.32-1.94, p trend <0.001). This result was replicated using plasma measurements after one-year. No interactions were detected with the nutritional intervention. Conclusion: Plasma 2-hydroxyglutarate, fumarate and malate levels were prospectively associated with increased cardiovascular risk. Clinical trial number: ISRCTN35739639. Santos JL, Ruiz-Canela M, Razquin C, Clish CB, Guasch-Ferré M, Babio N, et al. Circulating citric acid cycle metabolites and risk of cardiovascular disease in the PREDIMED study. Nutr Metab Cardiovasc Dis. 2023 Jan. 10.1016/j.numecd.2023.01.002 1590-3729 Nutrition, metabolism, and cardiovascular diseases : NMCD https://hdl.handle.net/20.500.13003/18861 36739229 L2022549540 2-s2.0-85148740184 https://hdl.handle.net/20.500.12105/23614 Circulating citric acid cycle metabolites and risk of cardiovascular disease in the PREDIMED study