Association of beta-hydroxybutyrate with development of heart failure: Sex differences in a Dutch population cohort

Jose L. Flores-Guerrero*, Berend Daan Westenbrink, Margery A. Connelly, James D. Otvos, Dion Groothof, Irina Shalaurova, Erwin Garcia, Gerjan Navis, Rudolf A. de Boer, Stephan J. L. Bakker, Robin P. F. Dullaart

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

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Background In the failing heart, energy metabolism is shifted towards increased ketone body oxidation. Nevertheless, the association of beta-hydroxybutyrate (beta-OHB) with development of heart failure (HF) remains unclear. We investigated the association between plasma beta-OHB and the risk of HF in a prospective population-based cohort.

Design Plasma beta-OHB concentrations were measured in 6134 participants of the PREVEND study. Risk of incident HF with reduced (HFrEF) or preserved (HFpEF) ejection fraction was estimated using multivariable-adjusted Cox regression models.

Results During median follow-up for 8.2 years, 227 subjects were diagnosed with HF (137 with HFrEF; 90 with HFpEF). Cox regression analyses revealed a significant association of higher beta-OHB concentrations with incident HF (HR per 1 standard deviation increase, 1.40 (95% CI: 1.21-1.63; P <.001), which was largely attributable to HFrEF. In women, the hazard ratio (HR) for HFrEF per 1 standard deviation increase in beta-OHB was 1.73 (95% confidence interval (CI): 1.17-2.56, P = .005) in age, BMI, type 2 diabetes, hypertension, myocardial infarction, smoking, alcohol consumption, total cholesterol, HDL-C, triglycerides, glucose, eGFR and UAE adjusted analysis. In men, in the same fully adjusted analysis, the HR was 1.14 (CI: 0.86-1.53, P = .36) (P <.01 for sex interaction). In N-terminal pro-brain natriuretic peptide (NT-proBNP)-stratified analysis, the age-adjusted association with HF was significant in women with higher NT-proBNP levels (P = .008).

Conclusions This prospective study suggests that high plasma concentrations of beta-OHB are associated with an increased risk of HFrEF, particularly in women. The mechanisms responsible for the sex differences of this association warrant further study.

Originele taal-2English
Pagina's (van-tot)1-11
Aantal pagina's11
TijdschriftEuropean Journal of Clinical Investigation
StatusPublished - 18-dec-2020

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