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Published on: May 8, 2018
Invasive Assessment of Coronary Artery Disease in Clonal Hematopoiesis of Indeterminate Potential
J Brett Heimlich1, Michael A Raddatz2, John Wells1
1Department of Medicine (J.B.H., J.W., S.O., M.T., K.F., E.B., K.U., Y.R.S., D.M.R., C.M.B., A.G.B.).
Insights
Clonal hematopoiesis of indeterminate potential (CHIP) is linked to increased risk of obstructive coronary artery disease, particularly affecting the left main and left anterior descending arteries. TET2 mutations show a higher risk for left main stenosis in CHIP patients.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Genetics
Background:
- Clonal hematopoiesis of indeterminate potential (CHIP) arises from acquired mutations in bone marrow progenitor cells.
- CHIP is associated with a doubled risk of atherosclerotic cardiovascular disease, but specific coronary phenotypes remain under-researched.
- Understanding the cardiovascular impact of CHIP is crucial for risk stratification and management.
Purpose of the Study:
- To define the coronary artery disease (CAD) phenotype in patients with CHIP using coronary angiography.
- To investigate the association between CHIP status and specific patterns of obstructive CAD.
- To identify if specific CHIP mutations confer differential risks for CAD phenotypes.
Main Methods:
- Recruited 1142 patients undergoing coronary angiography at Vanderbilt University Medical Center.
- Utilized DNA sequencing to determine CHIP status in all participants.
- Employed multivariable logistic regression and proportional odds models to analyze CHIP association with CAD phenotypes.
Main Results:
- 18.4% of patients undergoing coronary angiography were found to have CHIP.
- CHIP patients exhibited a significantly higher risk of obstructive left main (OR 2.44) and left anterior descending (OR 1.59) coronary artery disease.
- The ten eleven translocase 2 (TET2) CHIP mutation showed a greater effect size on left main stenosis compared to other CHIP mutations.
Conclusions:
- This study provides the first invasive assessment of CAD in CHIP, revealing an increased risk of obstructive left main and left anterior descending artery stenosis.
- TET2 mutation carriers with CHIP face a particularly elevated risk for left main stenosis.
- These findings contribute to understanding the enhanced morbidity and mortality associated with CHIP.
Background:
Clonal hematopoiesis of indeterminate potential (CHIP) occurs due to acquired mutations in bone marrow progenitor cells. CHIP confers a 2-fold risk of atherosclerotic cardiovascular disease. However, there are limited data regarding specific cardiovascular phenotypes. The purpose of this study was to define the coronary artery disease phenotype of the CHIP population-based on coronary angiography.
Methods:
We recruited 1142 patients from the Vanderbilt University Medical Center cardiac catheterization laboratory and performed DNA sequencing to determine CHIP status. Multivariable logistic regression models and proportional odds models were used to assess the association between CHIP status and angiography phenotypes.
Results:
We found that 18.4% of patients undergoing coronary angiography had a CHIP mutation. Those with CHIP had a higher risk of having obstructive left main (odds ratio, 2.44 [95% CI, 1.40-4.27]; P=0.0018) and left anterior descending (odds ratio, 1.59 [1.12-2.24]; P=0.0092) coronary artery disease compared with non-CHIP carriers. We additionally found that a specific CHIP mutation, ten eleven translocase 2 (TET2), has a larger effect size on left main stenosis compared with other CHIP mutations.
Conclusions:
This is the first invasive assessment of coronary artery disease in CHIP and offers a description of a specific atherosclerotic phenotype in CHIP wherein there is an increased risk of obstructive left main and left anterior descending artery stenosis, especially among TET2 mutation carriers. This serves as a basis for understanding enhanced morbidity and mortality in CHIP.
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