Clonal Hematopoiesis of Indeterminate Potential in Chronic Thromboembolic Pulmonary Hypertension: A Multicenter Study

BACKGROUND:
The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) is multifactorial and growing evidence has indicated that hematological disorders are involved. Clonal hematopoiesis of indeterminate potential (CHIP) has recently been associated with an increased risk of both hematological malignancies and cardiovascular diseases. However, the prevalence and clinical relevance of CHIP in patients with CTEPH remains unclear.

METHODS:
Using stepwise calling on next-generation sequencing data from 499 patients with CTEPH referred to 3 centers between October 2006 and December 2021, CHIP mutations were identified. We associated CHIP with all-cause mortality in patients with CTEPH. To provide insights into potential mechanisms, the associations between CHIP and inflammatory markers were also determined.

RESULTS:

In total, 47 (9.4%) patients with CTEPH carried at least 1 CHIP mutation at a variant allele frequency of ≥2%. The most common mutations were in
DNMT3A
,
TET2
,
RUNX1
, and
ASXL1
. During follow-up (mean, 55 months), deaths occurred in 22 (46.8%) and 104 (23.0%) patients in the CHIP and non-CHIP groups, respectively (
P
<0.001, log-rank test). The association of CHIP with mortality remained robust in the fully adjusted model (hazard ratio, 2.190 [95% CI, 1.257–3.816];
P
=0.006). Moreover, patients with CHIP mutations showed higher circulating interleukin-1β and interleukin-6 and lower interleukin-4 and IgG galactosylation levels.

CONCLUSIONS:
This is the first study to show that CHIP mutations occurred in 9.4% of patients with CTEPH are associated with a severe inflammatory state and confer a poorer prognosis in long-term follow-up.

Topics

No keywords indexed for this article. Browse by subject →

References

58

[1]

10.1183/13993003.02828-2020

[2]

Haemodynamic definitions and updated clinical classification of pulmonary hypertension

Gérald Simonneau, David Montani, David S. Celermajer et al.

European Respiratory Journal 10.1183/13993003.01913-2018

[3]

10.1160/th16-10-0790

[4]

10.1183/09031936.00009914

[5]

10.1007/s11239-015-1323-2

[6]

10.1183/09031936.00145013

[7]

10.1161/circresaha.117.310640

[8]

10.1016/j.thromres.2017.10.003

[9]

10.3390/ijms21093339

[10]

10.1161/jaha.120.015902

[11]

10.1038/leu.2016.85

[12]

10.1182/blood.2020008109

[13]

10.1164/rccm.202210-1941oc

[14]

10.1016/j.ejim.2019.08.004

[15]

10.1016/j.chest.2021.09.007

[16]

10.1016/j.jaccao.2022.04.002

[17]

Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes

David P. Steensma, Rafael Bejar, Siddhartha Jaiswal et al.

Blood 10.1182/blood-2015-03-631747

[18]

10.1161/circulationaha.120.051775

[19]

Clonal hematopoiesis in human aging and disease

Siddhartha Jaiswal, Benjamin L. Ebert

Science 10.1126/science.aan4673

[20]

10.1056/nejmoa1408617

[21]

Clonal Hematopoiesis and Risk of Atherosclerotic Cardiovascular Disease

Siddhartha Jaiswal, Pradeep Natarajan, Alexander J. Silver et al.

New England Journal of Medicine 10.1056/nejmoa1701719

[22]

10.1016/j.jacc.2021.04.085

[23]

10.1038/s41586-023-05857-4

[24]

10.1093/eurheartj/ehv317

[25]

10.1055/s-0039-1692428

[26]

10.1182/blood.2022018825

[27]

10.1021/pr4003992

[28]

10.1038/cr.2016.83

[29]

10.31083/j.fbl2707222

[30]

10.1126/science.aag1381

[31]

10.1161/circresaha.118.313225

[32]

10.1016/j.jacc.2017.12.037

[33]

10.1001/jamacardio.2020.2468

[34]

10.1016/j.jacc.2022.08.740

[35]

10.1161/hypertensionaha.123.21408

[36]

10.1038/s41598-017-12495-0

[37]

10.1001/jamacardio.2018.3965

[38]

10.1016/j.jacc.2021.02.028

[39]

10.1093/eurheartj/ehz591

[40]

10.1161/circulationaha.119.044320

[41]

10.1038/s41467-021-26435-0

[42]

10.1002/jcb.22249

[43]

10.1038/s41392-023-01520-6

[44]

10.1093/cvr/cvx161

[45]

10.1093/cvr/cvac001

[46]

10.1056/nejmoa1409405

[47]

10.1056/evidoa2200310

[48]

10.1161/strokeaha.121.037388

[49]

10.1001/jamacardio.2022.0386

[50]

10.1161/circulationaha.122.062126

Showing 50 of 58 references

Cited By

13

Clonal hematopoiesis of indeterminate potential as a prognostic factor: a systematic review and meta-analysis

Jasmine Singh, Nancy Li · 2024

Blood Advances

Metrics

13

Citations

58

References

Details

Published: Feb 01, 2024
Vol/Issue: 81(2)
Pages: 372-382

Authors

C

Chao Liu

Department of Cardiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (C.L., Y.-P.Z., X.-M.L., L.-H.Q., B.-C.Q., L.-Y.R., X.-Q.X., L.-F.C.), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Y

Yu-Ping Zhou

Department of Cardiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (C.L., Y.-P.Z., X.-M.L., L.-H.Q., B.-C.Q., L.-Y.R., X.-Q.X., L.-F.C.), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

T

Tian-Yu Lian

Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China (T.-Y.L., S.-J.Z., C.-Y.C., Z.-C.J).

R

Ruo-Nan Li

School of Pharmacy, Henan University, Zhengzhou, China (R.-N.L., J.-S.M.).

J

Jing-Si Ma

School of Pharmacy, Henan University, Zhengzhou, China (R.-N.L., J.-S.M.).

Y

Yin-Jian Yang

State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (Y.-J.Y., K.S., Z.-J.Z.), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

S

Si-Jin Zhang

Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China (T.-Y.L., S.-J.Z., C.-Y.C., Z.-C.J).

X

Xian-Mei Li

Department of Cardiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (C.L., Y.-P.Z., X.-M.L., L.-H.Q., B.-C.Q., L.-Y.R., X.-Q.X., L.-F.C.), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

L

Lu-Hong Qiu

Department of Cardiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (C.L., Y.-P.Z., X.-M.L., L.-H.Q., B.-C.Q., L.-Y.R., X.-Q.X., L.-F.C.), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

B

Bao-Chen Qiu

Department of Cardiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (C.L., Y.-P.Z., X.-M.L., L.-H.Q., B.-C.Q., L.-Y.R., X.-Q.X., L.-F.C.), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

L

Li-Yan Ren

Department of Cardiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (C.L., Y.-P.Z., X.-M.L., L.-H.Q., B.-C.Q., L.-Y.R., X.-Q.X., L.-F.C.), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

J

Jia Wang

Department of Medical Laboratory, Weifang Medical University, China (J.W.).

Z

Zhi-Yan Han

State Key Laboratory of Cardiovascular Disease, FuWai Hospital (Z.-Y.H., J.-H.L.), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

J

Jing-hui Li

State Key Laboratory of Cardiovascular Disease, FuWai Hospital (Z.-Y.H., J.-H.L.), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

L

Lan Wang

Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University, China (L.W.).

X

Xi-Qi Xu

Department of Cardiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (C.L., Y.-P.Z., X.-M.L., L.-H.Q., B.-C.Q., L.-Y.R., X.-Q.X., L.-F.C.), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

K

Kai Sun

State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (Y.-J.Y., K.S., Z.-J.Z.), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

L

Lian-Feng Chen

Department of Cardiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (C.L., Y.-P.Z., X.-M.L., L.-H.Q., B.-C.Q., L.-Y.R., X.-Q.X., L.-F.C.), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

C

Chun-Yan Cheng

Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China (T.-Y.L., S.-J.Z., C.-Y.C., Z.-C.J).

Z

Ze-Jian Zhang

State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital (Y.-J.Y., K.S., Z.-J.Z.), Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Z

Zhi-Cheng Jing

Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, China (T.-Y.L., S.-J.Z., C.-Y.C., Z.-C.J).

Cite This Article

Chao Liu, Yu-Ping Zhou, Tian-Yu Lian, et al. (2024). Clonal Hematopoiesis of Indeterminate Potential in Chronic Thromboembolic Pulmonary Hypertension: A Multicenter Study. Hypertension, 81(2), 372-382. https://doi.org/10.1161/hypertensionaha.123.22274

Clonal Hematopoiesis of Indeterminate Potential in Chronic Thromboembolic Pulmonary Hypertension: A Multicenter Study

You May Also Like