Clonal haematopoiesis of indeterminate potential predicts incident cardiac arrhythmias
Clonal haematopoiesis of indeterminate potential predicts incident cardiac arrhythmias
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DOI：
10.1093/eurheartj/ehad670
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发表时间：
2023-11-11
影响因子：
39.3
通讯作者：
Honigberg, Michael C.
中科院分区：
文献类型：
--
作者：
Schuermans, Art;Vlasschaert, Caitlyn;Honigberg, Michael C.
背景和目的不确定潜能的克隆性造血（CHIP），即具有白血病前突变的血细胞的年龄相关性扩增，与动脉粥样硬化性心血管疾病和心力衰竭相关。本研究旨在测试CHIP与新发arrhythmia.Methods英国生物样本库参与者没有普遍的心律失常的关联。共同主要研究结局为室上性心律失常、缓慢性心律失常和室性心律失常。次要结局为心脏骤停、房颤和任何心律失常。使用多变量校正的考克斯回归分析评估任何CHIP [变异等位基因分数（VAF）>= 2%]、大CHIP（VAF >= 10%）和基因特异性CHIP亚型与心律失常事件的相关性。CHIP与心肌间质纤维化的相关性[T1用心脏磁共振（CMR）测量]也被测试。结果本研究包括410702名参与者[CHIP：n = 13892（3.4%）;大CHIP：n = 9191（2.2%）]。任何和大CHIP与多变量校正的风险比相关，分别为1.11 [95%置信区间（CI）1.04-1.18; P = .001]和1.13（95% CI 1.05-1.22; P = .001）室上性心律失常，1.09（95% CI 1.01-1.19; P = .031）和1.13（95% CI 1.03-1.25; P = .011），室性心律失常分别为1.16（95% CI，1.00-1.34; P = .049）和1.22（95% CI 1.03-1.45; P = .021）。相关性独立于冠状动脉疾病和心力衰竭。心律失常亚型之间的相关性也是异质性的，心脏骤停的相关性最强。基因特异性分析显示，除DNMT 3A外，其他驱动基因的心律失常风险增加。大CHIP与1.31倍的几率相关（95% CI 1.07-1.59; P = .009）的心脏心肌纤维化的前五分之一CMR.结论CHIP可能代表了一个新的危险因素的事件心律失常，表明对心律失常的预防和治疗调制的潜在目标.结构化图形摘要在410 702中年成人从英国生物银行，不确定潜能的克隆性造血（CHIP）与心律失常事件相关，与其他心血管疾病如冠状动脉疾病和心力衰竭无关，与心脏骤停观察到的最强相关性。基因分层分析显示，除DNMT 3A外，其他驱动基因的心律失常风险增加。CI，置信区间; HR，风险比。
Background and Aims Clonal haematopoiesis of indeterminate potential (CHIP), the age-related expansion of blood cells with preleukemic mutations, is associated with atherosclerotic cardiovascular disease and heart failure. This study aimed to test the association of CHIP with new-onset arrhythmias.Methods UK Biobank participants without prevalent arrhythmias were included. Co-primary study outcomes were supraventricular arrhythmias, bradyarrhythmias, and ventricular arrhythmias. Secondary outcomes were cardiac arrest, atrial fibrillation, and any arrhythmia. Associations of any CHIP [variant allele fraction (VAF) >= 2%], large CHIP (VAF >= 10%), and gene-specific CHIP subtypes with incident arrhythmias were evaluated using multivariable-adjusted Cox regression. Associations of CHIP with myocardial interstitial fibrosis [T1 measured using cardiac magnetic resonance (CMR)] were also tested.Results This study included 410 702 participants [CHIP: n = 13 892 (3.4%); large CHIP: n = 9191 (2.2%)]. Any and large CHIP were associated with multi-variable-adjusted hazard ratios of 1.11 [95% confidence interval (CI) 1.04-1.18; P = .001] and 1.13 (95% CI 1.05-1.22; P = .001) for supraventricular arrhythmias, 1.09 (95% CI 1.01-1.19; P = .031) and 1.13 (95% CI 1.03-1.25; P = .011) for bradyarrhythmias, and 1.16 (95% CI, 1.00-1.34; P = .049) and 1.22 (95% CI 1.03-1.45; P = .021) for ventricular arrhythmias, respectively. Associations were independent of coronary artery disease and heart failure. Associations were also heterogeneous across arrhythmia subtypes and strongest for cardiac arrest. Gene-specific analyses revealed an increased risk of arrhythmias across driver genes other than DNMT3A. Large CHIP was associated with 1.31-fold odds (95% CI 1.07-1.59; P = .009) of being in the top quintile of myocardial fibrosis by CMR.Conclusions CHIP may represent a novel risk factor for incident arrhythmias, indicating a potential target for modulation towards arrhythmia prevention and treatment.Structured Graphical Abstract In 410 702 middle-aged adults from the UK Biobank, clonal haematopoiesis of indeterminate potential (CHIP) was associated with incident arrhythmias independent of other cardiovascular diseases such as coronary artery disease and heart failure, with the strongest associations observed for cardiac arrest. Gene-stratified analyses revealed an increased risk of arrhythmias across driver genes other than DNMT3A. CI, confidence interval; HR, hazard ratio.