Abstract 16989: Clonal Hematopoiesis of Indeterminate Potential Status is Associated With Left Main Artery Stenosis

Abstract

Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) occurs secondary to acquired mutations in bone marrow progenitor cells. CHIP confers a twofold risk of atherosclerotic cardiovascular disease (ASCVD). The two most common CHIP mutations are ten eleven translocase 2 (TET2) and DNA methyltransferase 3A (DNMT3A). However, there is limited data on specific cardiovascular phenotypes in this population. Methods: We recruited patients from the Vanderbilt University Medical Center cardiac catheterization laboratory and performed next generation sequencing to assign CHIP status. Multivariable logistic regression models and proportional odds models were used to assess the association between CHIP status and coronary angiography. Results: We sequenced 1,469 patients, and 1,149 had complete angiographic data. Of these, 214 (18.6%) had CHIP mutations with a variant allele frequency of >2%. CHIP patients were significantly older (68 vs. 59 years, p = 7.7 x 10-16). CHIP carrier status was significantly correlated with any stenosis and degree of stenosis in the left main (LM) coronary artery (OR 1.87 [1.28-2.74]; P = 0.0013 and OR 2.12 [1.42-3.15]; P = 2.2 x 10-4). This association was stronger among patients with TET2 CHIP, both for any LM stenosis (OR 2.98 [1.48 - 5.96]; P = 0.0021) and the degree of LM stenosis (OR 3.52 [1.78 - 6.95]; P = 2.9 x 10-4) (Fig. 1). TET2 CHIP was also correlated with obstructive (>70%) stenosis in any vessel (OR 2.28 [1.15 - 4.52]; P = 0.019), and the number of obstructive stenoses across coronary vessels (OR 1.83 [1.04 - 3.23]; P = 0.037). Conclusions: 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. Our findings reveal a population enriched for CHIP carriers in the catheterization laboratory, an important observation for future studies focused on secondary prevention in CHIP-related ASCVD.