Zhang Nan, Liu Daiqi, Zhao Jinhua, Tse Gary, Zhou Jiandong, Zhang Qingpeng, Lip Gregory Y H, Liu Tong
Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China.
Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China; School of Nursing and Health Studies, Hong Kong Metropolitan University, Hong Kong, China; Cardiovascular Analytics Group, PowerHealth Research Institute, Hong Kong, China.
Heart Rhythm. 2025 Sep;22(9):2245-2256. doi: 10.1016/j.hrthm.2024.10.028. Epub 2024 Oct 19.
Ketone bodies (KBs) are an important cardiac metabolic energy source. Metabolic remodeling has recently been found to play an important role in the pathological process of atrial fibrillation (AF).
The purpose of this study was to evaluate the associations of circulating KB levels with incident AF risk in the general population.
We studied 237,163 participants [mean age, 56.5 years; 129,472 women (55%)] from the UK Biobank who were free of AF at baseline and had data on circulating β-hydroxybutyrate (β-OHB), acetoacetate, and acetone. The associations of KBs with new-onset AF were evaluated using Cox regression in the general population and across the 3 genetic risk groups: low, moderate, and high polygenic risk score of AF.
During a median follow-up of 14.8 (13.8, 15.5) years, 16,638 participants (7.0%) developed AF. There was a U-shaped association of total KBs and β-OHB with incident AF, with nadirs at 60.6 and 40.8 μmol/L, respectively (P < .05), whereas there was a positive association of acetoacetate and acetone with AF (P < .001; P > .05). Consistently, there was a U-shaped association of total KBs and β-OHB with left atrial (LA) volume parameters, including LA maximum volume, LA minimum volume, and their body surface area-indexed counterparts, and there was an inverted U-shaped association of total KBs and β-OHB with LA ejection fraction (P < .05 for all). The associations of KBs with AF were stronger in individuals with low genetic risk (P < .05), while the highest AF risk was in those with high genetic risk with high KB levels. Significant mediation effects of inflammatory markers on the associations between KBs and AF were identified.
There was a U-shaped association of circulating total KBs and β-OHB with incident AF as well as a positive association of acetoacetate and acetone levels with AF risk in the general population.
酮体（KBs）是心脏重要的代谢能量来源。最近发现代谢重塑在心房颤动（AF）的病理过程中起重要作用。
本研究旨在评估普通人群中循环KB水平与AF发病风险之间的关联。
我们研究了英国生物银行的237,163名参与者[平均年龄56.5岁；129,472名女性（55%）]，这些参与者在基线时无AF，并拥有循环β-羟基丁酸（β-OHB）、乙酰乙酸和丙酮的数据。在普通人群以及3个遗传风险组（AF低、中、高多基因风险评分）中，使用Cox回归评估KBs与新发AF的关联。
在中位随访14.8（13.8，15.5）年期间，16,638名参与者（7.0%）发生了AF。总KBs和β-OHB与新发AF呈U形关联，最低点分别为60.6和40.8μmol/L（P <.05），而乙酰乙酸和丙酮与AF呈正相关（P <.001；P>.05）。同样，总KBs和β-OHB与左心房（LA）容积参数呈U形关联，包括LA最大容积、LA最小容积及其体表面积指数对应值，总KBs和β-OHB与LA射血分数呈倒U形关联（所有P <.05）。KBs与AF的关联在低遗传风险个体中更强（P <.05），而AF风险最高的是高遗传风险且KB水平高的个体。炎症标志物对KBs与AF之间的关联具有显著的中介作用。
在普通人群中，循环总KBs和β-OHB与新发AF呈U形关联，乙酰乙酸和丙酮水平与AF风险呈正相关。
