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Circulating Ketone Bodies and Incident Cardiovascular Outcomes and Mortality: Insights From the UK Biobank

Parag Anilkumar Chevli1, Saeid Mirzai1, Richard Kazibwe2

  • 1Department of Cardiovascular Medicine Wake Forest University School of Medicine Winston-Salem NC USA.

Journal of the American Heart Association
|February 20, 2026
PubMed

Insights

Higher ketone bodies (KB) are linked to increased risk of cardiovascular events and mortality. This study in a large population found elevated KB levels correlated with higher rates of atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and death.

Area of Science:

  • Cardiovascular Medicine
  • Metabolic Health
  • Biochemistry

Background:

  • Ketone bodies (KB) are vital endogenous energy sources produced by the liver during metabolic stress.
  • The precise impact of KB on atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and mortality remains unclear.
  • This research investigates the relationship between KB levels and new cardiovascular outcomes in a general population without pre-existing ASCVD or HF.

Purpose of the Study:

  • To determine the association between endogenous ketone body levels and the incidence of cardiovascular disease (CVD) and mortality.
  • To analyze the risk of specific cardiovascular events, including ASCVD, HF, myocardial infarction, and stroke, in relation to KB levels.
  • To evaluate the association of KB with all-cause mortality and cardiovascular death.

Main Methods:

  • Utilized data from 90,987 participants in the UK Biobank, all free from prevalent ASCVD or HF.
  • Measured total ketone bodies (KB) using nuclear magnetic resonance spectroscopy.
  • Employed multivariable-adjusted Cox proportional hazards models to assess the association between KB and primary outcomes (ASCVD, HF, all-cause death) and secondary outcomes over a median follow-up of 13.4 years.

Main Results:

  • Higher ketone body (KB) levels were significantly associated with an increased risk of incident atherosclerotic cardiovascular disease (ASCVD) (HR, 1.31), heart failure (HF) (HR, 1.44), and all-cause mortality (HR, 1.51) per 10-fold increase.
  • A notable increase in the risk of stroke (37%) and cardiovascular disease (CVD) death (69%) was observed with higher KB levels.
  • No significant association was found between KB levels and the incidence of myocardial infarction.

Conclusions:

  • Elevated endogenous ketone bodies (KB) in individuals without baseline cardiovascular disease (CVD) are linked to a higher risk of developing ASCVD, HF, and stroke.
  • Higher KB levels are associated with an increased risk of all-cause mortality and CVD death.
  • The findings highlight a potential role for KB in cardiovascular risk stratification and management.
Abstract

Keywords:
atherosclerotic cardiovascular diseaseheart failureketone bodiesmortality

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