Key result
Elevated ketone body ratio linked to ~60% greater incident HF risk in older men.
Why the study?
Ketone bodies are an important alternative energy source for the heart implicated in cardiovascular disease, but their relationship with incident HF in older men required determination.
Does an elevated ketone body ratio predict incident heart failure in older men without prior MI or HF?
Cohort (n=3,459)
Does an elevated ketone body ratio predict incident heart failure in older men without prior MI or HF?
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An elevated ketone body ratio (acetoacetate to β-hydroxybutyrate) is an independent biomarker for incident heart failure in older men, particularly when NT-proBNP is also elevated.
Aims Ketone bodies (KB), acetoacetate and β-hydroxybutyrate, are an important fat-derived alternative energy source for the heart and have been implicated in the pathogenesis of cardiovascular disease. The study aimed to determine the relationship between total KB (acetoacetate + β-hydroxybutyrate) and KB ratio (acetoacetate: β-hydroxybutyrate) with incident HF in older men. Methods 3459 men without prevalent myocardial infarction or HF from the prospective cohort British Regional Heart Study were included in the analysis. KB levels were measured by nuclear magnetic resonance spectroscopy. Participants were followed up for a median 15.9 years. Results 375 men developed HF. Total KB was not significantly associated with incident HF (age-adjusted standardised hazards ratio (HR) (95%CI) 0.94 [0.84–1.04], p=0.231 for trend). However, KB ratio was significantly associated with incident HF (age-adjusted standardised HR (95%CI) 1.12 [1.01–1.24], p=0.023 for trend). Risk tended to increase with increasing levels of KB ratio from 0.35 with risk significantly raised when the KB ratio was above 0.55 (top decile) even after adjustment for traditional cardiovascular risk factors, inflammatory markers, and NT-proBNP [HR (95%CI) for KB ratio >0.55 vs <0.18 (bottom quartile) =1.60 (1.13–2.27), p=0.008]. The increased risk associated with elevated KB ratio was more evident in the younger men (age < 70 years). When examined by levels of NT-proBNP, elevated KB ratio was significantly associated with increased HF risk only in the presence of elevated NT-proBNP (>83pg/ml; above the median) [age-adjusted HR=1.87 (1.25-2.81)]. Weaker associations were seen in those without raised NT-proBNP [HR=1.23 (0.66-2.27)]. Conclusion Elevated KB ratio is associated with a significantly increased risk of HF incidence independent of established cardiovascular risk factors and inflammatory markers. Elevated KB ratio may serve as a biomarker of HF incidence particularly when NT-proBNP is also elevated.
Saadeh et al. (2026) conducted a cohort in Heart failure (n=3,459). Ketone body ratio (acetoacetate: β-hydroxybutyrate) vs. Lower ketone body ratio was evaluated on Incident heart failure (HR 1.12, 95% CI 1.01-1.24, p=0.023). An elevated ketone body ratio was significantly associated with an increased risk of incident heart failure in older men (HR 1.12; 95% CI 1.01-1.24; p=0.023 for trend).
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