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- Title
Association of beta-hydroxybutyrate with development of heart failure: Sex differences in a Dutch population cohort.
- Authors
Flores-Guerrero, Jose L.; Westenbrink, Berend Daan; Connelly, Margery A.; Otvos, James D.; Groothof, Dion; Shalaurova, Irina; Garcia, Erwin; Navis, Gerjan; de Boer, Rudolf A.; Bakker, Stephan J. L.; Dullaart, Robin P. F.
- Abstract
Background: In the failing heart, energy metabolism is shifted towards increased ketone body oxidation. Nevertheless, the association of beta-hydroxybutyrate (β- OHB) with development of heart failure (HF) remains unclear. We investigated the association between plasma β-OHB and the risk of HF in a prospective populationbased cohort. Design: Plasma β-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 β-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 β-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 β-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.
- Subjects
HEART failure; BRAIN natriuretic factor; 3-Hydroxybutyric acid; ALCOHOL drinking; TYPE 2 diabetes; HDL cholesterol; EPIDERMAL growth factor receptors
- Publication
European Journal of Clinical Investigation, 2021, Vol 51, Issue 5, p1
- ISSN
0014-2972
- Publication type
Article
- DOI
10.1111/eci.13468