Circulating beta-hydroxybutyrate levels in advanced heart failure with reduced ejection fraction: Determinants and prognostic impact.

Autor: Monzo L; Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic.; Université de Lorraine, Centre d'Investigations Cliniques Plurithématique 1433 and Inserm U1116, CHRU Nancy, FCRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France., Kovar J; Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic., Borlaug BA; Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA., Benes J; Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic., Kotrc M; Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic., Kroupova K; Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic., Jabor A; Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic., Franekova J; Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic., Melenovsky V; Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic.
Jazyk: angličtina
Zdroj: European journal of heart failure [Eur J Heart Fail] 2024 Sep; Vol. 26 (9), pp. 1931-1940. Date of Electronic Publication: 2024 Jun 10.
DOI: 10.1002/ejhf.3324
Abstrakt: Aims: Patients with heart failure (HF) display metabolic alterations, including heightened ketogenesis, resulting in increased beta-hydroxybutyrate (β-OHB) formation. We aimed to investigate the determinants and prognostic impact of circulating β-OHB levels in patients with advanced HF and reduced ejection fraction (HFrEF).
Methods and Results: A total of 867 patients with advanced HFrEF (age 57 ± 11 years, 83% male, 45% diabetic, 60% New York Heart Association class III), underwent clinical and echocardiographic examination, circulating metabolite assessment, and right heart catheterization (n = 383). The median β-OHB level was 64 (interquartile range [IQR] 33-161) μmol/L (normal 0-74 μmol/L). β-OHB levels correlated with increased markers of lipolysis (free fatty acids [FFA]), higher natriuretic peptides, worse pulmonary haemodynamics, and lower humoral regulators of ketogenesis (insulin/glucagon ratio). During a median follow-up of 1126 (IQR 410-1781) days, there were 512 composite events, including 324 deaths, 81 left ventricular assist device implantations and 107 urgent cardiac transplantations. In univariable Cox regression, increased β-OHB levels (T3 vs. T1: hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.13-1.72, p = 0.002) and elevated FFA levels (T3 vs. T1: HR 1.39, 95% CI 1.09-1.79, p = 0.008) were both predictors of a worse prognosis. In multivariable Cox analysis evaluating the simultaneous associations of FFA and β-OHB levels with outcomes, only FFA levels remained significantly associated with adverse outcomes.
Conclusions: In patients with advanced HFrEF, increased plasma β-OHB correlate with FFA levels, worse right ventricular function, greater neurohormonal activation and other markers of HF severity. The association between plasma β-OHB and adverse outcomes is eliminated after accounting for FFA levels, suggesting that increased β-OHB is a consequence reflecting heightened lipolytic state, rather than a cause of worsening HF.
(© 2024 European Society of Cardiology.)
Databáze: MEDLINE
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