EClinicalMedicine (Aug 2024)
Clonal hematopoiesis of indeterminate potential and the risk of pulmonary embolism: an observational studyResearch in context
Abstract
Summary: Background: 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. Methods: 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 DNMT3A, TET2, ASXL1, PPM1D, SRSF2, and JAK2. Findings: 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 TET2 (HR 1.42, 95% CI 1.16–1.74) or JAK2 (HR 4.17, 95% CI 2.09–8.35) mutation, but not for DNMT3A mutation (HR 1.01, 95% CI 0.86–1.19), ASXL1 mutation (HR 1.15, 95% CI 0.83–1.60), PPM1D mutation (HR 1.22, 95% CI 0.66–2.27), or SRSF2 mutation (HR 0.62, 95% CI 0.20–1.93). Interpretation: Our results highlight the association of pulmonary embolism in individuals with CHIP, especially the TET2-mutant or JAK2-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. Funding: 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).
