Clonal Hematopoiesis is Associated with Adverse Events in Patients with High-Grade Carotid Artery Stenosis

Introduction Clonal hematopoiesis (CH), defined as the expansion of a subset of hematopoietic stem or progenitor cells driven by acquired mutations, represents a novel cardiovascular risk factor. Its role in patients with high-grade carotid stenosis remains to be evaluated. Patients and Methods Next-generation sequencing (NGS) involving 30 genes implicated in CH was used as diagnostic-grade assay (SOPHiA DDM Myeloid Solution) to screen for CH in 83 prospectively collected patients with symptomatic or asymptomatic high-grade carotid stenosis undergoing carotid endarterectomy (CEA). Results Clonal markers were detected in 16 (19.7%) of 83 patients (median age 71.2 years), with prevalence increasing at advanced age. At 5-year follow-up, CH carriers showed a higher cumulative incidence of major adverse cardiovascular events (MACE; P=0.040) compared to patients without CH; all-cause mortality did not differ significantly between groups (P=0.57). Cox regression revealed a significant association between CH and MACE in a univariable model (P=0.047), which remained significant after multivariable adjustment for age and sex (P=0.018). Exploratory analyses suggested that the association between CH and MACE may differ according to carotid stenosis severity, with an increased incidence of MACE observed in patients with <90% stenosis and concomitant CH, an effect absent in patients with ≥90% stenosis ( P interaction =0.03). Discussion and Conclusions CH was associated with an adverse 5-year outcome in patients with carotid artery stenosis. These findings identify CH as a hematologic contributor to post-interventional cardiovascular risk and indicate that assessment of CH may offer additional prognostic information for residual risk stratification.