Elevated Plasma Levels of Ketone Bodies Are Associated With All‐Cause Mortality and Incidence of Heart Failure in Older Adults: The CHS
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 energ...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-09-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.123.029960 |
| _version_ | 1797689831457816576 |
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| author | Sebastian Niezen Margery A. Connelly Calvin Hirsch Jorge R. Kizer Maria E. Benitez Scott Minchenberg Maria Camila Perez‐Matos Zhenghui Gordon Jiang Kenneth J. Mukamal |
| author_facet | Sebastian Niezen Margery A. Connelly Calvin Hirsch Jorge R. Kizer Maria E. Benitez Scott Minchenberg Maria Camila Perez‐Matos Zhenghui Gordon Jiang Kenneth J. Mukamal |
| author_sort | Sebastian Niezen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T01:51:22Z |
| format | Article |
| id | doaj.art-880462c4e1c548aa8425718fa4f19ea2 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-03-12T01:51:22Z |
| publishDate | 2023-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-880462c4e1c548aa8425718fa4f19ea22023-09-08T12:39:35ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802023-09-01121710.1161/JAHA.123.029960Elevated Plasma Levels of Ketone Bodies Are Associated With All‐Cause Mortality and Incidence of Heart Failure in Older Adults: The CHSSebastian Niezen0Margery A. Connelly1Calvin Hirsch2Jorge R. Kizer3Maria E. Benitez4Scott Minchenberg5Maria Camila Perez‐Matos6Zhenghui Gordon Jiang7Kenneth J. Mukamal8Department of Medicine University of Pittsburgh Medical Center, University of Pittsburgh Pittsburgh PALaboratory Corporation of America Holdings Morrisville NCDepartment of General Internal Medicine University of California Davis Health Sacramento CACardiac Section, San Francisco Veterans Affairs Health Care System, Departments of Medicine, and Epidemiology and Biostatistics University of California San Francisco San Francisco CADepartment of Internal Medicine Advocate Illinois Masonic Medical Center Chicago ILDepartment of Medicine, Beth Israel Deaconess Medical Center Harvard Medical School Boston MADepartment of Molecular Metabolism Harvard T.H. Chan School of Public Health Boston MADepartment of Medicine, Beth Israel Deaconess Medical Center Harvard Medical School Boston MADepartment of Medicine, Beth Israel Deaconess Medical Center Harvard Medical School Boston MABackground 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.https://www.ahajournals.org/doi/10.1161/JAHA.123.029960agingheart failureketone bodiesmetabolismmortality |
| spellingShingle | Sebastian Niezen Margery A. Connelly Calvin Hirsch Jorge R. Kizer Maria E. Benitez Scott Minchenberg Maria Camila Perez‐Matos Zhenghui Gordon Jiang Kenneth J. Mukamal Elevated Plasma Levels of Ketone Bodies Are Associated With All‐Cause Mortality and Incidence of Heart Failure in Older Adults: The CHS Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease aging heart failure ketone bodies metabolism mortality |
| title | Elevated Plasma Levels of Ketone Bodies Are Associated With All‐Cause Mortality and Incidence of Heart Failure in Older Adults: The CHS |
| title_full | Elevated Plasma Levels of Ketone Bodies Are Associated With All‐Cause Mortality and Incidence of Heart Failure in Older Adults: The CHS |
| title_fullStr | Elevated Plasma Levels of Ketone Bodies Are Associated With All‐Cause Mortality and Incidence of Heart Failure in Older Adults: The CHS |
| title_full_unstemmed | Elevated Plasma Levels of Ketone Bodies Are Associated With All‐Cause Mortality and Incidence of Heart Failure in Older Adults: The CHS |
| title_short | Elevated Plasma Levels of Ketone Bodies Are Associated With All‐Cause Mortality and Incidence of Heart Failure in Older Adults: The CHS |
| title_sort | elevated plasma levels of ketone bodies are associated with all cause mortality and incidence of heart failure in older adults the chs |
| topic | aging heart failure ketone bodies metabolism mortality |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.123.029960 |
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