Liu Qianwei, Smedby Karin Ekström, Xue Huiwen, Wästerlid Tove, Li Jiong, Fang Fang, Liu Xinyuan
Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Clinical Medical Research Center of Hematology Diseases of Guangdong Province, Guangzhou, China.
EClinicalMedicine. 2024 Jul 26;74:102753. doi: 10.1016/j.eclinm.2024.102753. eCollection 2024 Aug.
Pulmonary embolism causes a substantial burden of morbidity and mortality. Although there are several well-established risk factors for pulmonary embolism, a substantial proportion of cases cannot be attributed to provoked or known risk factors. Accumulating evidence has suggested an association of clonal hematopoiesis of indeterminate potential (CHIP) with the risk of arterial thromboembolism. However, the association between CHIP and the risk of pulmonary embolism remains unknown.
We performed a community-based cohort study (between 2006 and 2022) including 464,417 individuals with available whole exome sequencing (WES) data in the UK biobank (UKB) to examine the association between CHIP and pulmonary embolism. CHIP was ascertained by analyzing WES data. We used Cox regression models to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) to assess the association between CHIP and pulmonary embolism. In addition, we performed analyses for several types of CHIP mutations, including , , , , , and .
The study included 14,418 individuals with CHIP and 449,999 individuals without CHIP. The median age at cohort entry was 58 and 63 years among individuals without and with CHIP, respectively. We observed an increased risk of pulmonary embolism (HR 1.17, 95% CI, 1.05-1.31) among individuals with CHIP. The increased risk was mainly noted for CHIP with (HR 1.42, 95% CI 1.16-1.74) or (HR 4.17, 95% CI 2.09-8.35) mutation, but not for mutation (HR 1.01, 95% CI 0.86-1.19), mutation (HR 1.15, 95% CI 0.83-1.60), mutation (HR 1.22, 95% CI 0.66-2.27), or mutation (HR 0.62, 95% CI 0.20-1.93).
Our results highlight the association of pulmonary embolism in individuals with CHIP, especially the -mutant or mutant CHIP. If further studies will identify a causal relationship between clonal hematopoiesis and pulmonary embolism, prioritizing early screening for pulmonary embolism in individuals with CHIP could be significantly beneficial.
Initial Founding for High Level Talented Scholars in Nanfang Hospital, Southern Medical University (No. 2023G001) and the Outstanding Youths Development Scheme of Nanfang Hospital, Southern Medical University (Grant No. 2023J009).
肺栓塞会导致相当大的发病和死亡负担。尽管有几种公认的肺栓塞危险因素，但相当一部分病例无法归因于诱发因素或已知危险因素。越来越多的证据表明，具有不确定潜能的克隆性造血（CHIP）与动脉血栓栓塞风险相关。然而，CHIP与肺栓塞风险之间的关联尚不清楚。
我们进行了一项基于社区的队列研究（2006年至2022年），纳入了英国生物银行（UKB）中464417名有全外显子测序（WES）数据的个体，以研究CHIP与肺栓塞之间的关联。通过分析WES数据确定CHIP。我们使用Cox回归模型计算风险比（HRs）及95%置信区间（CIs），以评估CHIP与肺栓塞之间的关联。此外，我们对几种类型的CHIP突变进行了分析，包括 、 、 、 、 、和 。
该研究纳入了14418名有CHIP的个体和449999名无CHIP的个体。队列入组时，无CHIP个体的中位年龄为58岁，有CHIP个体的中位年龄为63岁。我们观察到有CHIP的个体发生肺栓塞的风险增加（HR 1.17，95% CI，1.05 - 1.31）。风险增加主要见于具有 （HR 1.42，95% CI 1.16 - 1.74）或 （HR 4.17，95% CI 2.09 - 8.35）突变的CHIP，但 突变（HR 1.01，95% CI 0.86 - 1.19）、 突变（HR 1.15，95% CI 0.83 - 1.60）、 突变（HR 1.22，95% CI 0.66 - 2.27）或 突变（HR 0.62，95% CI 0.20 - 1.93）的CHIP个体未出现风险增加。
我们的结果突出了CHIP个体中肺栓塞的关联，特别是 - 突变或 突变的CHIP。如果进一步的研究能够确定克隆性造血与肺栓塞之间的因果关系，对CHIP个体优先进行肺栓塞早期筛查可能会带来显著益处。
南方医科大学南方医院高层次人才学者初始基金（编号2023G001）和南方医科大学南方医院优秀青年发展计划（资助编号2023J009）。
