Jiang Zaixin, Li Yi, Yan Chenghui, Zhang Xiaolin, Zhang Quanyu, Li Jing, Tian Xiaoxiang, Qiu Miaohan, Liang Zhenyang, Ma Sichong, Na Kun, Li Ziqi, Chen Sanbao, Zhao Yu, Qi Zizhao, Liu Xiying, Han Yaling
The Department of Cardiology, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang, 110016, Liaoning Province, China.
The Department of Cardiology, Naval Medical University Changhai Hospital, Shanghai, China.
Clin Res Cardiol. 2023 Apr;112(4):506-517. doi: 10.1007/s00392-022-02039-6. Epub 2022 Jun 15.
To investigate the frequency of clonal hematopoiesis of indeterminate potential (CHIP) and evaluate its impacts on outcomes in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) in the absence of traditional cardiovascular risk factors (CVRFs).
Whole-exome sequencing was performed to detect the presence of CHIP in 183 patients underwent PCI for the treatment of ACS. The association between CHIP-related mutations and major adverse cardiac or cerebral events (MACCEs, a composite of all-cause mortality, coronary revascularization, myocardial infarction, or stroke) was analyzed in such cohort.
Of 179 patients [median age, 65 years; 84 female (46.9%)] included in this analysis, CHIP-related mutations were detected in 36 (20.1%) patients. The somatic mutations most frequently occurred in the genes DNMT3A (17 mutations), TET2 (6 mutations), and ASXL1 (4 mutations). Clinical outcomes at median 635 follow-up days showed that DNMT3A/TET2/ASXL1-CHIP mutations were associated with significantly higher risk of MACCEs, compared with non-CHIP carriers in the CVRFs-absent ACS cohort (26.1% vs. 4.2%, log-rank P = 0.001). Multivariable regression showed that DNMT3A/TET2/ASXL1-CHIP driver mutations (HR 4.015; 95% CI 1.236-13.046; P = 0.021) were independent predictors of adverse clinical outcomes.
The most frequent CHIP-related mutations, DNMT3A, TET2, and ASXL1 are significantly associated with increased risk of recurrent cardiovascular events. Our study may be valuable target to reduce residual risk in patients with ACS carrying specific mutations.
研究不确定潜能克隆性造血（CHIP）的频率，并评估其对无传统心血管危险因素（CVRF）的急性冠状动脉综合征（ACS）患者接受经皮冠状动脉介入治疗（PCI）后预后的影响。
对183例因ACS接受PCI治疗的患者进行全外显子组测序，以检测CHIP的存在。在该队列中分析CHIP相关突变与主要不良心脑血管事件（MACCE，全因死亡、冠状动脉血运重建、心肌梗死或中风的综合指标）之间的关联。
本分析纳入的179例患者[中位年龄65岁；84例女性（46.9%）]中，36例（20.1%）患者检测到CHIP相关突变。体细胞突变最常发生在DNMT3A基因（17个突变）、TET2基因（6个突变）和ASXL1基因（4个突变）。中位随访635天的临床结果显示，在无CVRF的ACS队列中，与非CHIP携带者相比，DNMT3A/TET2/ASXL1-CHIP突变与MACCE风险显著升高相关（26.1%对4.2%，对数秩检验P = 0.001）。多变量回归显示，DNMT3A/TET2/ASXL1-CHIP驱动突变（HR 4.015；95%CI 1.236 - 13.046；P = 0.021）是不良临床结局的独立预测因素。
最常见的CHIP相关突变DNMT3A、TET2和ASXL1与复发性心血管事件风险增加显著相关。我们的研究可能是降低携带特定突变的ACS患者残余风险的有价值靶点。
