Mutations in CHIP-associated genes at myeloid neoplasm diagnosis and risk of cardiovascular/cerebrovascular events

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP)-associated somatic mutations are associated with increased cardiovascular and cerebrovascular risk in the general population; whether mutations detected at myeloid neoplasm (MN) diagnosis predict incident cardiovascular and cerebrovascular events (CCVEs) is unclear. METHODS: We retrospectively studied 203 adults with newly diagnosed myelodysplastic neoplasms, myelodysplastic/myeloproliferative neoplasms, or acute myeloid leukemia unfit for intensive chemotherapy (2016-2023) who underwent pretreatment next-generation sequencing. Cause-specific hazard models adjusted for cardiovascular risk factors assessed associations between CHIP-associated gene mutations and incident CCVEs, including age-stratified and age-by-mutation interaction analyses. RESULTS: =0.29). In multivariable models, CHIP-associated gene mutations, higher-risk MN, and incident CCVEs were each associated with higher all-cause mortality. CONCLUSIONS: CHIP-associated gene mutations at MN diagnosis were not independently associated with incident CCVEs. Older mutation-positive patients had higher observed CCVE risk, predominantly heart failure, with limited precision. These exploratory findings warrant prospective multicenter validation.