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Association of beta-hydroxybutyrate with development of heart failure: Sex differences in a Dutch population cohort.
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.
Affiliation
  • Flores-Guerrero JL; Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Westenbrink BD; Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Connelly MA; Laboratory Corporation of America Holdings (LabCorp), Morrisville, NC, USA.
  • Otvos JD; Laboratory Corporation of America Holdings (LabCorp), Morrisville, NC, USA.
  • Groothof D; Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Shalaurova I; Laboratory Corporation of America Holdings (LabCorp), Morrisville, NC, USA.
  • Garcia E; Laboratory Corporation of America Holdings (LabCorp), Morrisville, NC, USA.
  • Navis G; Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • de Boer RA; Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Bakker SJL; Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Dullaart RPF; Department of Internal Medicine, Division of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Eur J Clin Invest ; 51(5): e13468, 2021 May.
Article in En | MEDLINE | ID: mdl-33616911
BACKGROUND: In the failing heart, energy metabolism is shifted towards increased ketone body oxidation. Nevertheless, the association of beta-hydroxybutyrate (ß-OHB) with development of heart failure (HF) remains unclear. We investigated the association between plasma ß-OHB and the risk of HF in a prospective population-based cohort. DESIGN: Plasma ß-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 ß-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 ß-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 ß-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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: 3-Hydroxybutyric Acid / Heart Failure Type of study: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Adult / Aged / Female / Humans / Male / Middle aged Country/Region as subject: Europa Language: En Journal: Eur J Clin Invest Year: 2021 Type: Article Affiliation country: Netherlands

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: 3-Hydroxybutyric Acid / Heart Failure Type of study: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Adult / Aged / Female / Humans / Male / Middle aged Country/Region as subject: Europa Language: En Journal: Eur J Clin Invest Year: 2021 Type: Article Affiliation country: Netherlands