Abstract 4366635: Clonal hematopoiesis of indeterminate potential in coronary disease patients: a 24-year follow-up

Abstract

Cardiovascular disease (CVD) is highly prevalent and remains a cause of great morbi-mortality worldwide. Growing evidence suggests clonal hematopoiesis of indeterminate potential (CHIP) as an independent cardiovascular risk factor worsening overall survival (OS). However, actual data either comes from large population databases with heterogenous and/or poorly defined CVD or from smaller better-defined populations but with limited follow-up. We aimed to thoroughly characterize the extent and severity of coronary artery disease (CAD) and OS in CHIP-positive patients using the COROL (COROonary disease cLinico-biological determinants study) cohort which included patients undergoing coronarography and for which we now have up to 24 years of follow-up. We also evaluated if OS in CHIP-positive patients was similar depending on CAD treatment. We retrospectively analyzed data from the 2050 COROL patients included between 2000-2001 at CHU de Lille in France (mean age (standard deviation): 61 (12) years, men: 76.2%). Our primary focus was CAD lesions (% of stenosis) by coronarography, treatment (medical, angioplasty or surgery), CHIP (variant allele frequency (VAF) ≥2%, determined using a 70-gene NGS panel) and OS. Patients with no significant coronary lesion (<50%) served as controls. Statistical analysis for preliminary results included log-rank and Student analysis. Of the 1976/2050 patients that met inclusion criteria, CHIP was found in 28.5%. DNMT3a , TET2 and ASXL1 accounted for two-third of the mutated genes. Preliminary results in 1466/1976 patients showed reduced median OS in CHIP-negative patients with ≥50% lesions compared to those with <50% lesions (p=0.0007). Median OS was worse in both CHIP-positive groups with no difference according to CAD status (table 1). Moreover, no CAD treatment could reverse CHIP effect (figure 1). Our study is the first to provide detailed information on CAD extent and treatment in CHIP-positive patients while offering 20+ years of follow-up. It shows an independent negative effect of CHIP on OS, which raises concerns about CHIP identification and CAD patients management.