Clonal hematopoiesis of indeterminate potential in patients with acute coronary syndrome undergoing percutaneous coronary intervention in the absence of traditional risk factors
Aims 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). Metho...
Saved in:
Published in | Clinical research in cardiology Vol. 112; no. 4; pp. 506 - 517 |
---|---|
Main Authors | , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Berlin/Heidelberg
Springer Berlin Heidelberg
01.04.2023
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Aims
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).
Methods
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.
Results
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.
Conclusion
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.
Graphical abstract |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1861-0684 1861-0692 |
DOI: | 10.1007/s00392-022-02039-6 |