TCA cycle metabolites associated with adverse outcomes after acute coronary syndrome: mediating effect of renal function.

Autor:	Sanchez-Gimenez R; Department of Cardiology, Joan XXIII University Hospital, Tarragona, Spain.; Institute of Health Pere Virgili (IISPV), Tarragona-Reus, Spain.; Department of Medicine and Surgery, Rovira I Virgili University, Tarragona, Spain., Peiró ÓM; Department of Cardiology, Joan XXIII University Hospital, Tarragona, Spain.; Institute of Health Pere Virgili (IISPV), Tarragona-Reus, Spain.; Department of Medicine and Surgery, Rovira I Virgili University, Tarragona, Spain., Bonet G; Department of Cardiology, Joan XXIII University Hospital, Tarragona, Spain.; Institute of Health Pere Virgili (IISPV), Tarragona-Reus, Spain.; Department of Medicine and Surgery, Rovira I Virgili University, Tarragona, Spain., Carrasquer A; Department of Cardiology, Joan XXIII University Hospital, Tarragona, Spain.; Institute of Health Pere Virgili (IISPV), Tarragona-Reus, Spain.; Department of Medicine and Surgery, Rovira I Virgili University, Tarragona, Spain., Fragkiadakis GA; Department of Nutrition and Dietetics Sciences, School of Health Sciences, Hellenic Mediterranean University, Siteia, Greece., Bulló M; Institute of Health Pere Virgili (IISPV), Tarragona-Reus, Spain.; Nutrition and Metabolic Health Research Group, Department of Biochemistry and Biotechnology, Rovira I Virgili University, Reus, Spain.; Center of Environmental, Food and Toxicological Technology - TecnATox, Rovira i Virgili University, Reus, Spain.; CIBER Physiology of Obesity and Nutrition (CIBEROBN), Carlos III Health Institute, Madrid, Spain., Papandreou C; Institute of Health Pere Virgili (IISPV), Tarragona-Reus, Spain.; Department of Nutrition and Dietetics Sciences, School of Health Sciences, Hellenic Mediterranean University, Siteia, Greece.; Nutrition and Metabolic Health Research Group, Department of Biochemistry and Biotechnology, Rovira I Virgili University, Reus, Spain.; Center of Environmental, Food and Toxicological Technology - TecnATox, Rovira i Virgili University, Reus, Spain., Bardaji A; Department of Cardiology, Joan XXIII University Hospital, Tarragona, Spain.; Institute of Health Pere Virgili (IISPV), Tarragona-Reus, Spain.; Department of Medicine and Surgery, Rovira I Virgili University, Tarragona, Spain.
Jazyk:	angličtina
Zdroj:	Frontiers in cardiovascular medicine [Front Cardiovasc Med] 2023 Jun 27; Vol. 10, pp. 1157325. Date of Electronic Publication: 2023 Jun 27 (Print Publication: 2023).
DOI:	10.3389/fcvm.2023.1157325
Abstrakt:	Aims: To examine relationships of tricarboxylic acid (TCA) cycle metabolites with risk of cardiovascular events and mortality after acute coronary syndrome (ACS), and evaluate the mediating role of renal function in these associations. Methods: This is a prospective study performed among 309 ACS patients who were followed for a mean of 6.7 years. During this period 131 patients developed major adverse cardiovascular events (MACE), defined as the composite of myocardial infarction, hospitalization for heart failure, and all-cause mortality, and 90 deaths were recorded. Plasma concentrations of citrate, aconitate, isocitrate, succinate, malate, fumarate, α-ketoglutarate and d/l-2-hydroxyglutarate were quantified using LC-tandem MS. Multivariable Cox regression models were used to estimate hazard ratios, and a counterfactual-based mediation analysis was performed to test the mediating role of estimated glomerular filtration rate (eGFR). Results: After adjustment for traditional cardiovascular risk factors and medications, positive associations were found between isocitrate and MACE (HR per 1 SD, 1.25; 95% CI: 1.03, 1.50), and between aconitate, isocitrate, d/l-2-hydroxyglutarate and all-cause mortality (HR per 1 SD, 1.41; 95% CI: 1.07, 1.84; 1.58; 95% CI: 1.23, 2.02; 1.38; 95% CI: 1.14, 1.68). However, these associations were no longer significant after additional adjustment for eGFR. Mediation analyses demonstrated that eGFR is a strong mediator of these associations. Conclusion: These findings underscore the importance of TCA metabolites and renal function as conjunctive targets in the prevention of ACS complications. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (© 2023 Sanchez-Gimenez, Peiró, Bonet, Carrasquer, Fragkiadakis, Bulló, Papandreou and Bardaji.)
Databáze:	MEDLINE
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