Circulating ketone bodies and mortality in heart failure: a community cohort study

Abstract

BackgroundThe relationship between ketone bodies (KB) and mortality in patients with heart failure (HF) syndrome has not been well established.ObjectivesThe aim of this study is to assess the distribution of KB in HF, identify clinical correlates, and examine the associations between plasma KB and all-cause mortality in a population-based HF cohort.MethodsThe plasma KB levels were measured by nuclear magnetic resonance spectroscopy. Multivariable linear regression was used to examine associations between clinical correlates and KB levels. Proportional hazard regression was employed to examine associations between KB (represented as both continuous and categorical variables) and mortality, with adjustment for several clinical covariates.ResultsAmong the 1,382 HF patients with KB measurements, the median (IQR) age was 78 (68, 84) and 52% were men. The median (IQR) KB was found to be 180 (134, 308) μM. Higher KB levels were associated with advanced HF (NYHA class III–IV) and higher NT-proBNP levels (both P < 0.001). The median follow-up was 13.9 years, and the 5-year mortality rate was 51.8% [95% confidence interval (CI): 49.1%–54.4%]. The risk of death increased when KB levels were higher (HRhigh vs. low group 1.23; 95% CI: 1.05–1.44), independently of a validated clinical risk score. The association between higher KB and mortality differed by ejection fraction (EF) and was noticeably stronger among patients with preserved EF.ConclusionsMost patients with HF exhibited KB levels that were consistent with those found in healthy adults. Elevated levels of KB were observed in patients with advanced HF. Higher KB levels were found to be associated with an increased risk of death, particularly in patients with preserved EF.