Li Jiannan, Chen Runzhen, Zhou Jinying, Li Nan, Zhou Peng, Liu Chen, Song Li, Zhao Xiaoxiao, Chen Yi, Yan Shaodi, Yan Hongbing, Tan Yu, Zhao Hanjun
Department of Cardiology, Peking Union Medical College &, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Beijing, China.
Department of Cardiology, Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.
Genome Med. 2025 Aug 25;17(1):94. doi: 10.1186/s13073-025-01531-8.
Clonal hematopoiesis of indeterminate potential (CHIP) is related to cardiovascular disorders and poor prognosis. However, the relationship between CHIP and clinical outcome as well as pathological phenotype of patients with acute myocardial infarction was unknown. Herein, we aimed to investigate the associations between CHIP mutation stratified by variant allele frequency (VAF) from 0.5% to 2% and the incidence of major adverse cardiovascular events (MACE) as well as the characteristics of culprit lesions in patients with ST-segment elevation myocardial infarction (STEMI).
Targeted deep sequencing with a unique molecular identifier (UMI) was used to examine CHIP with VAFs greater than 0.5%, 1%, and 2% in prospective cohort including a total of 1403 patients with STEMI, and MACE including all-cause death, myocardial infarction, stroke, and unplanned revascularization during follow-up was recorded. In addition, the morphology of culprit plaques detected by optical coherence tomography (OCT) in 355 patients with de novo lesions were evaluated via image analysis.
The CHIP mutation frequency in each VAF stratification increased with increasing age. Patients with either TET2 or ASXL1 CHIP mutations presented significantly greater mortality than those without for VAF > 2%, 1%, and 0.5% (17.1% vs. 10.1%, p = 0.0001; 17.0% vs. 10.3%, p = 0.0464; and 17.8% vs. 9.8%, p = 0.0025 for VAF > 2%, 1%, and 0.5%, respectively). For other MACE including myocardial infarction, stroke and unplanned revascularization, no significant difference was observed. Simultaneous assessment of CHIP and systemic inflammation revealed combined effects on all-cause mortality, depicted by significant higher risk for patients with high-sensitivity C-reactive protein level > 5.8 mg/L and concomitant CHIP. Moreover, subgroup analysis revealed that patients with CHIP mutations got greater clinical benefit of ticagrelor and statin than those without CHIP. Additionally, patients with TET2/ASXL1 VAFs of > 0.5% and 1% were significantly prone to exhibit a greater prevalence of ruptured fibrous cap in culprit lesions than those without (33 [70.2%] vs. 145 [47.1%], p = 0.0031; 16 [72.7%] vs. 162 [48.6%], p = 0.0287).
TET2/ASXL1 CHIP mutations with VAF > 2% combined with high inflammatory status were indicative of high mortality in patients with STEMI. Additionally, TET2/ASXL1 mutation with a VAF > 0.5% favored the recognition of vulnerable plaque features in patients with STEMI.
不确定潜能克隆造血（CHIP）与心血管疾病及不良预后相关。然而，CHIP与急性心肌梗死患者的临床结局及病理表型之间的关系尚不清楚。在此，我们旨在研究按变异等位基因频率（VAF）从0.5%至2%分层的CHIP突变与ST段抬高型心肌梗死（STEMI）患者主要不良心血管事件（MACE）发生率以及罪犯病变特征之间的关联。
在包括总共1403例STEMI患者的前瞻性队列中，使用带有独特分子标识符（UMI）的靶向深度测序来检测VAF大于0.5%、1%和2%的CHIP，并记录随访期间包括全因死亡、心肌梗死、中风和非计划血管重建在内的MACE。此外，通过图像分析评估了355例新发病变患者经光学相干断层扫描（OCT）检测的罪犯斑块形态。
每个VAF分层中的CHIP突变频率随年龄增长而增加。对于VAF > 2%、1%和0.5%，TET2或ASXL1 CHIP突变患者的死亡率显著高于无突变患者（VAF > 2%时为17.1%对10.1%，p = 0.0001；VAF > 1%时为17.0%对10.3%，p = 0.0464；VAF > 0.5%时为17.8%对9.8%，p = 0.0025）。对于包括心肌梗死、中风和非计划血管重建在内的其他MACE，未观察到显著差异。CHIP与全身炎症的同时评估显示对全因死亡率有联合影响，高敏C反应蛋白水平> 5.8 mg/L且伴有CHIP的患者风险显著更高。此外，亚组分析显示，有CHIP突变的患者比无CHIP突变的患者从替格瑞洛和他汀类药物中获得更大的临床益处。另外，TET2/ASXL1 VAF > 0.5%和1%的患者比无突变患者的罪犯病变中纤维帽破裂的患病率显著更高（分别为33 [70.2%]对145 [47.1%]，p = 0.0031；16 [72.7%]对162 [48.6%]，p = 0.0287）。
VAF > 2%的TET2/ASXL1 CHIP突变与高炎症状态相结合表明STEMI患者死亡率高。此外，VAF > 0.5%的TET2/ASXL1突变有利于识别STEMI患者的易损斑块特征。
