Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Eur J Clin Invest. 2021 May;51(5):e13468. doi: 10.1111/eci.13468. Epub 2020 Dec 18.
In the failing heart, energy metabolism is shifted towards increased ketone body oxidation. Nevertheless, the association of beta-hydroxybutyrate (β-OHB) with development of heart failure (HF) remains unclear. We investigated the association between plasma β-OHB and the risk of HF in a prospective population-based cohort.
Plasma β-OHB concentrations were measured in 6134 participants of the PREVEND study. Risk of incident HF with reduced (HFrEF) or preserved (HFpEF) ejection fraction was estimated using multivariable-adjusted Cox regression models.
During median follow-up for 8.2 years, 227 subjects were diagnosed with HF (137 with HFrEF; 90 with HFpEF). Cox regression analyses revealed a significant association of higher β-OHB concentrations with incident HF (HR per 1 standard deviation increase, 1.40 (95% CI: 1.21-1.63; P < .001), which was largely attributable to HFrEF. In women, the hazard ratio (HR) for HFrEF per 1 standard deviation increase in β-OHB was 1.73 (95% confidence interval (CI): 1.17-2.56, P = .005) in age, BMI, type 2 diabetes, hypertension, myocardial infarction, smoking, alcohol consumption, total cholesterol, HDL-C, triglycerides, glucose, eGFR and UAE adjusted analysis. In men, in the same fully adjusted analysis, the HR was 1.14 (CI: 0.86-1.53, P = .36) (P < .01 for sex interaction). In N-terminal pro-brain natriuretic peptide (NT-proBNP)-stratified analysis, the age-adjusted association with HF was significant in women with higher NT-proBNP levels (P = .008).
This prospective study suggests that high plasma concentrations of β-OHB are associated with an increased risk of HFrEF, particularly in women. The mechanisms responsible for the sex differences of this association warrant further study.
在衰竭的心脏中，能量代谢会转向增加酮体的氧化。然而，β-羟丁酸（β-OHB）与心力衰竭（HF）的发展之间的关联仍不清楚。我们在一项前瞻性的基于人群的队列研究中调查了血浆β-OHB 与 HF 风险之间的关系。
在 PREVEND 研究的 6134 名参与者中测量了血浆β-OHB 浓度。使用多变量调整的 Cox 回归模型估计了射血分数降低（HFrEF）或保留（HFpEF）的HF 的发病风险。
在中位 8.2 年的随访期间，227 名受试者被诊断为 HF（137 例为 HFrEF；90 例为 HFpEF）。Cox 回归分析显示，较高的β-OHB 浓度与 HF 的发生显著相关（每增加 1 个标准差的 HR，1.40（95%CI：1.21-1.63；P<0.001），这主要归因于 HFrEF。在女性中，β-OHB 每增加 1 个标准差，HFrEF 的危险比（HR）为 1.73（95%置信区间（CI）：1.17-2.56，P=0.005），在年龄、BMI、2 型糖尿病、高血压、心肌梗死、吸烟、饮酒、总胆固醇、HDL-C、甘油三酯、血糖、eGFR 和 UAE 调整分析中。在男性中，在相同的完全调整分析中，HR 为 1.14（CI：0.86-1.53，P=0.36）（性别交互作用 P<0.01）。在 N 末端脑钠肽前体（NT-proBNP）分层分析中，在较高 NT-proBNP 水平的女性中，HF 的年龄调整相关性具有统计学意义（P=0.008）。
这项前瞻性研究表明，高血浆β-OHB 浓度与 HFrEF 风险增加相关，尤其是在女性中。这种关联的性别差异的机制需要进一步研究。
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