Heart failure & cardiomyopathiesCohort study

Inflammatory and catabolic activity mediate the association of plasma β-hydroxybutyrate and mortality in heart failure

ESC Heart FailPublished

  • cohort

Authors' conclusion

Elevated β-hydroxybutyrate levels predict mortality in chronic HF, independent of established risk factors. Proteomic analysis links elevated β-hydroxybutyrate to heightened inflammation and catabolism, and these pathways largely mediated the association between β-hydroxybutyrate and mortality. These findings suggest that elevated ketone bodies may reflect underlying metabolic stress in patients at risk of adverse outcome.

Study context

Population
Patients with heart failure (HF) from the BIOSTAT-CHF cohortpatients with HF with plasma β-hydroxybutyrate measured
Participants
478 patients
Exposure
Association of plasma β-hydroxybutyrate with mortality and HF hospitalization

Main finding

As reported in the abstract

Cohort characteristics

Male patients

64.2%

Observational data: associations, not effects.

Further findings

OutcomeEstimate
Mortality per doubling of β-hydroxybutyrate — every doubling of β-hydroxybutyrate · 36.4% increase in mortalityunadjusted hazard ratio 1.364 (95% CI 1.089–1.707)
Mortality per doubling of β-hydroxybutyrate — every doubling of β-hydroxybutyrate · after accounting for known risk factorsadjusted hazard ratio 1.389 (95% CI 1.150–1.677)

Correlates of elevated β-hydroxybutyrate

Independently associated with higher heart rate, lower iron levels, and lower body mass index

Differential expression and ingenuity pathway analyses

Higher β-hydroxybutyrate associated with upregulation of pathways associated with acute inflammation and cachexia; lipogenic and anabolic pathways down-regulated

Multiple mediation analysis

Share of association between β-hydroxybutyrate and mortality explained by these pathways
76%

Original publication

Inflammatory and catabolic activity mediate the association of plasma β-hydroxybutyrate and mortality in heart failure. ESC Heart Fail. Published 21 September 2026. doi:10.1093/eschf/xvag193

Summarised from the published abstract; every number is checked against it