Circulating ketone bodies, genetic susceptibility, with left atrial remodeling and atrial fibrillation: A prospective study from the UK Biobank

IF 5.7 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Heart rhythm Pub Date : 2025-09-01 Epub Date: 2024-10-19 DOI:10.1016/j.hrthm.2024.10.028

Nan Zhang BS , Daiqi Liu BS , Jinhua Zhao BS , Gary Tse MD, PhD , Jiandong Zhou PhD , Qingpeng Zhang PhD , Gregory Y.H. Lip MD , Tong Liu MD, PhD

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Abstract

Background

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).

Objective

The purpose of this study was to evaluate the associations of circulating KB levels with incident AF risk in the general population.

Methods

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.

Results

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_nonlinear < .05), whereas there was a positive association of acetoacetate and acetone with AF (P_overall < .001; P_nonlinear > .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_nonlinear < .05 for all). The associations of KBs with AF were stronger in individuals with low genetic risk (P_interaction < .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.

Conclusion

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.

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循环酮体、遗传易感性、左心房结构、功能和心房颤动：英国生物数据库前瞻性研究。

背景：酮体（KB）是重要的心脏代谢能量来源。最近有研究指出，代谢重塑在心房颤动（AF）的病理过程中起着重要作用：评估普通人群中循环 KB 水平与房颤发病风险之间的关系：我们研究了英国生物库中的 237,163 名参与者（平均年龄 56.5 岁；55% 为女性），这些人基线时没有房颤，并掌握了循环中的β-羟丁酸（β-OHB）、乙酰乙酸和丙酮数据。在普通人群和三个遗传风险组（房颤的低度、中度和高度多基因风险评分）中，通过 Cox 回归评估了 KB 与新发房颤之间的关联：在中位 14.8 年的随访期间，16638 人（7.0%）患上了房颤。总 KB 和 β-OHB 与心房颤动的发生呈 U 型关系，最低点分别为 60.6 和 40.8 μmol/L（P 非线性 0.05）。同样，在总 KB 和 β-OHB 与左心房（LA）容积参数（包括 LA 最大容积（LAVmax）、LA 最小容积（LAVmin）及其体表面积指数对应值）之间观察到 U 型关联，在 LA 射血分数方面观察到倒 U 型关联（所有 P 均为非线性交互作用结论）：在普通人群中，循环总KB和β-OHB与房颤发病率呈U形关系，乙酰乙酸和丙酮水平与房颤风险呈正相关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Heart rhythm 医学-心血管系统

CiteScore

10.50

自引率

5.50%

发文量

1465

审稿时长

24 days

期刊介绍： HeartRhythm, the official Journal of the Heart Rhythm Society and the Cardiac Electrophysiology Society, is a unique journal for fundamental discovery and clinical applicability. HeartRhythm integrates the entire cardiac electrophysiology (EP) community from basic and clinical academic researchers, private practitioners, engineers, allied professionals, industry, and trainees, all of whom are vital and interdependent members of our EP community. The Heart Rhythm Society is the international leader in science, education, and advocacy for cardiac arrhythmia professionals and patients, and the primary information resource on heart rhythm disorders. Its mission is to improve the care of patients by promoting research, education, and optimal health care policies and standards.