Background and Aims: Aging is associated with the acquisition of genetic abnormalities in hematopoietic stem cells, leading to the development of a clonal hematopoiesis (CH) in absence of hematological disease. These abnormalities can be somatic mutations, as observed in clonal hematopoiesis of indeterminate potential (CHIP) or chromosomal abnormalities, such as mosaic loss of the Y chromosome (mLOY). Both CHIP and mLOY have been associated with an increased cardiovascular risk, but the effect of the combination of both types of genetic alterations in a single subject remains unknown. In this study, we sought to determine whether mLOY can modulate the impact of CHIP on systemic inflammation, atherosclerosis burden or incidence of myocardial infarction (MI). Methods: We analyzed 218 male subjects aged 65 or more at inclusion from 2 prospective cohorts : CHAth (NCT04581057) and subjects from 3 City study. CRP level and atheromatous burden (atheromatous volume, carotid stenosis >50%, number of atheromatous plaques, intima-media thickness) were assessed at inclusion. The presence of CHIP and mLOY was searched by high-throughput sequencing and digital PCR respectively. Results: Forty five percent of subjects carried a CHIP, 40% a mLOY, and 17.8% had both CHIP and mLOY, without significant association between both types of CH. There was no significant association between CHIP+/-mLOY and the CRP level or atheromatous burden. Similar results were observed in patients with or without a history of CVE at inclusion. CHIP were associated with an accelerated MI occurrence, more importantly in the absence of mLOY. Conclusions: In our cohort, neither CHIP nor mLOY were associated with an increased systemic inflammation or increased atheromatous burden. In subjects with CHIP, mLOY seems to delay MI occurrence. These observations need to be confirmed in a larger cohort of patients.< Leer menos