Clonal Hematopoiesis of Indeterminate Potential Status is Associated with Left Main Artery Stenosis

Clonal hematopoiesis of indeterminate potential (CHIP) occurs as a result of acquired mutations in bone marrow progenitor cells. CHIP confers a twofold risk of atherosclerotic cardiovascular disease (ASCVD). However, there is limited data regarding specific cardiovascular phenotypes in this population. We recruited patients from the Vanderbilt University Medical Center cardiac catheterization laboratory and performed next generation sequencing to determine CHIP status. Multivariable logistic regression models and proportional odds models were used to assess the association between CHIP status and coronary angiography. We find nearly 1 in 5 patients undergoing coronary angiography have a CHIP mutation. Those with CHIP had a higher risk of having left main coronary artery disease compared to non-CHIP carriers. We additionally find that those with a specific CHIP mutation, ten eleven translocase 2 (TET2) has a larger effect size on left main stenosis compared with other CHIP mutations. This is the first description of a specific atherosclerotic phenotype in CHIP and serves as a basis for understanding enhanced morbidity and mortality in CHIP.