02812nas a2200325   4500008004100000022001400041245014100055210006900196260001600265300001200281490000700293520182800300653000902128653001002137653002802147653001802175653001102193653001402204653001802218100002202236700002502258700001902283700002002302700002202322700002302344700003102367700002802398700002402426856003602450       2023                        eng d  a2047-998000aElevated Plasma Levels of Ketone Bodies Are Associated With All-Cause Mortality and Incidence of Heart Failure in Older Adults: The CHS.0 aElevated Plasma Levels of Ketone Bodies Are Associated With AllC  c2023 Sep 05  ae0299600 v123 a<p>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]; =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]; =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]; =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.</p>10aAged10aAging10aCardiovascular Diseases10aHeart Failure10aHumans10aIncidence10aKetone Bodies1 aNiezen, Sebastian1 aConnelly, Margery, A1 aHirsch, Calvin1 aKizer, Jorge, R1 aBenitez, Maria, E1 aMinchenberg, Scott1 aPerez-Matos, Maria, Camila1 aJiang, Zhenghui, Gordon1 aMukamal, Kenneth, J  uhttps://chs-nhlbi.org/node/9485