Department of Medicine University of Pittsburgh Medical Center, University of Pittsburgh Pittsburgh PA.
Laboratory Corporation of America Holdings Morrisville NC.
J Am Heart Assoc. 2023 Sep 5;12(17):e029960. doi: 10.1161/JAHA.123.029960. Epub 2023 Aug 23.
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.
慢性疾病（如心力衰竭）会影响细胞代谢并塑造循环代谢物。关键能量代谢物与衰老相关慢性疾病之间的关系尚未得到很好的理解。本研究旨在确定能量代谢主要成分与全因死亡率和心力衰竭事件之间的关系。
我们分析了美国老年人 CHS（心血管健康研究）中血浆代谢物水平与全因死亡率和心力衰竭事件之间的关系。我们对基线时无心力衰竭的 1758 名参与者进行了随访，分析了分析物水平与代谢谱之间的关系，代谢谱特征为酮体水平升高与全因死亡率和心力衰竭事件有关。多变量 Cox 分析显示，酮体浓度最低和最高五分位数之间全因死亡率呈 50%的剂量反应关系（HR，1.5 [95%CI，1.0-1.9]；=0.007）。在调整心血管疾病混杂因素后，酮体水平仍与心力衰竭事件相关（HR，1.2 [95%CI，1.0-1.3]；=0.02）。使用 K-均值聚类分析，我们确定了一个具有较高酮体、柠檬酸、白细胞介素-6 和 B 型利钠肽水平但较低丙酮酸、体重指数和估计肾小球滤过率水平的聚类。酮体水平升高的聚类与全因死亡率较高相关（HR，1.7 [95%CI，1.1-2.7]；=0.01）。
在一个美国老年人群中，较高的酮体浓度可预测心力衰竭和全因死亡率，独立于代谢和心血管混杂因素。这种相关性表明酮体代谢与衰老之间存在潜在的重要关系。
