부산대학교 도서관

Introduction: Clonal hematopoiesis of indeterminate potential (CHIP), the expansion of hematopoietic stem cells harboring a leukemogenic mutation without blood cancer, is associated with accelerated atherosclerosis in large datasets. The clinical impact of underlying CHIP mutations on clinical presentation and outcomes among those with atherosclerotic cardiovascular disease (ASCVD) events is unknown.Methods: We included patients in the Mass General Brigham Biobank with available whole exome sequences who experienced a first ASCVD event (coronary artery disease [CAD], cerebrovascular, or peripheral artery event) following or within 6 months before blood sample collection. Individuals with CHIP (variant allele fraction >2%) were matched 1:2 with CHIP-free patients by qualifying ASCVD subtype, age, sex, race, current/former smoking, and type 2 diabetes. Clinical characteristics, management, and subsequent outcomes were abstracted by chart review.Results: The sample (N=120) included 40 individuals with and 80 without CHIP (overall mean age 64.1 years), of whom 99 (82.5%) had CAD as the qualifying event. The most common CHIP drivers were DNMT3A (32.5%), TET2 (30.0%), and PPM1D (15.0%). Median (IQR) calculated 10-year ASCVD risk was 13.4% (6.9-19.5%) in those with CHIP vs. 15.5% (9.6-22.7%) in those without. Among individuals with CAD, burden of obstructed major coronary arteries on angiography was unexpectedly lower in those with CHIP (P=0.04), as were rates of revascularization. Over a median 4.1 years of follow-up after the index event, the composite of acute coronary syndrome, stroke, peripheral artery disease, and mortality occurred in 35.0% with CHIP vs. 25.0% without (P=0.29), including in 50.0% with PPM1D, 33.3% with TET2, and 23.1% with DNMT3A CHIP.Conclusions: CHIP may be prognostic among those with ASCVD events. Future larger studies should characterize mechanisms of first and recurrent events and heterogeneity across CHIP subtypes.