Nan Zhang, Daiqi Liu, Jinhua Zhao, Gary Tse, Jiandong Zhou, Qingpeng Zhang, Gregory Y H Lip, Tong Liu
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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.</p><p><strong>Results: </strong>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<sub>nonlinear</sub> < .05), whereas there was a positive association of acetoacetate and acetone with AF (P<sub>overall</sub> < .001; P<sub>nonlinear</sub> > .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<sub>nonlinear</sub> < .05 for all). The associations of KBs with AF were stronger in individuals with low genetic risk (P<sub>interaction</sub> < .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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":5,"journal":{"name":"ACS Applied Materials & Interfaces","volume":null,"pages":null},"PeriodicalIF":8.3000,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Circulating ketone bodies, genetic susceptibility, with left atrial remodeling and atrial fibrillation: A prospective study from the UK Biobank.\",\"authors\":\"Nan Zhang, Daiqi Liu, Jinhua Zhao, Gary Tse, Jiandong Zhou, Qingpeng Zhang, Gregory Y H Lip, Tong Liu\",\"doi\":\"10.1016/j.hrthm.2024.10.028\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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).</p><p><strong>Objective: </strong>The purpose of this study was to evaluate the associations of circulating KB levels with incident AF risk in the general population.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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<sub>nonlinear</sub> < .05), whereas there was a positive association of acetoacetate and acetone with AF (P<sub>overall</sub> < .001; P<sub>nonlinear</sub> > .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<sub>nonlinear</sub> < .05 for all). The associations of KBs with AF were stronger in individuals with low genetic risk (P<sub>interaction</sub> < .05), while the highest AF risk was in those with high genetic risk with high KB levels. 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引用次数: 0
摘要
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。
Circulating ketone bodies, genetic susceptibility, with left atrial remodeling and atrial fibrillation: A prospective study from the UK Biobank.
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 (Pnonlinear < .05), whereas there was a positive association of acetoacetate and acetone with AF (Poverall < .001; Pnonlinear > .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 (Pnonlinear < .05 for all). The associations of KBs with AF were stronger in individuals with low genetic risk (Pinteraction < .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.
期刊介绍：
ACS Applied Materials & Interfaces is a leading interdisciplinary journal that brings together chemists, engineers, physicists, and biologists to explore the development and utilization of newly-discovered materials and interfacial processes for specific applications. Our journal has experienced remarkable growth since its establishment in 2009, both in terms of the number of articles published and the impact of the research showcased. We are proud to foster a truly global community, with the majority of published articles originating from outside the United States, reflecting the rapid growth of applied research worldwide.
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