Elevated plasma levels of ketone bodies are associated with all-cause mortality and incidence of heart failure in older adults: The CHS

Authors

Sebastian Niezen, Department of Medicine University of Pittsburgh Medical Center, University of Pittsburgh Pittsburgh PA.
Margery A. Connelly, Laboratory Corporation of America Holdings Morrisville NC.
Calvin Hirsch, Department of General Internal Medicine University of California Davis Health Sacramento CA.
Jorge R. Kizer, Cardiac Section, San Francisco Veterans Affairs Health Care System, Departments of Medicine, and Epidemiology and Biostatistics University of California San Francisco San Francisco CA.
Maria E. Benitez, Advocate Aurora HealthFollow
Scott Minchenberg, Department of Medicine, Beth Israel Deaconess Medical Center Harvard Medical School Boston MA.
Maria Camila Perez-Matos, Department of Molecular Metabolism Harvard T.H. Chan School of Public Health Boston MA.
Zhenghui Gordon Jiang, Department of Medicine, Beth Israel Deaconess Medical Center Harvard Medical School Boston MA.
Kenneth J. Mukamal, Department of Medicine, Beth Israel Deaconess Medical Center Harvard Medical School Boston MA.

Recommended Citation

Niezen S, Connelly MA, Hirsch C, et al. Elevated Plasma Levels of Ketone Bodies Are Associated With All-Cause Mortality and Incidence of Heart Failure in Older Adults: The CHS. J Am Heart Assoc. 2023;12(17):e029960. doi:10.1161/JAHA.123.029960

Affiliations

Advocate Illinois Masonic Medical Center

Abstract

Background Chronic disease, such as heart failure, influences cellular metabolism and shapes circulating metabolites. The relationships between key energy metabolites and chronic diseases in aging are not well understood. This study aims to determine the relationship between main components of energy metabolism with all-cause mortality and incident heart failure. Methods and Results We analyzed the association between plasma metabolite levels with all-cause mortality and incident heart failure among US older adults in the CHS (Cardiovascular Health Study). We followed 1758 participants without heart failure at baseline with hazard ratios (HRs) of analyte levels and metabolic profiles characterized by high levels of ketone bodies for all-cause mortality and incident heart failure. Multivariable Cox analyses revealed a dose-response relationship of 50% increase in all-cause mortality between lowest and highest quintiles of ketone body concentrations (HR, 1.5 [95% CI, 1.0-1.9]; P=0.007). Ketone body levels remained associated with incident heart failure after adjusting for cardiovascular disease confounders (HR, 1.2 [95% CI, 1.0-1.3]; P=0.02). Using K-means cluster analysis, we identified a cluster with higher levels of ketone bodies, citrate, interleukin-6, and B-type natriuretic peptide but lower levels of pyruvate, body mass index, and estimated glomerular filtration rate. The cluster with elevated ketone body levels was associated with higher all-cause mortality (HR, 1.7 [95% CI, 1.1-2.7]; P=0.01). Conclusions Higher concentrations of ketone bodies predict incident heart failure and all-cause mortality in an older US population, independent of metabolic and cardiovascular confounders. This association suggests a potentially important relationship between ketone body metabolism and aging.

Type

Article

PubMed ID

37609928