Abstract
INTRODUCTION: Clonal haematopoiesis of indeterminate potential (CHIP) has been reported to increase the risk of various diseases, including cardiovascular diseases (CVDs). In contrast, a newly published study suggests that CHIP itself may not directly contribute to the risks of CVDs or other age-related conditions. CHIP could also serve as a protective factor against certain diseases, such as Alzheimer's disease. However, protective effects of CHIP against CVDs have rarely been investigated. OBJECTIVES: To demonstrate the associations with CHIP and lower angina pectoris (AP) risk especially unstable angina pectoris (UAP), and explore potential mechanisms. METHODS: This study was carried out based on UK Biobank cohort. General linear models adjusted for covariates were used to detect associations between CHIP and AP. Propensity score matching models were used for validation. Mendelian randomization was utilized for causality inference. Mediation analysis was conducted to explore underlying mechanisms of cytokines level. RESULTS: In covariate models, large overall CHIP was associated with reduced AP and UAP risk. Large TET2 CHIP reduced AP and UAP risk. Propensity score matching models confirmed that large TET2 CHIP protected against AP and UAP. Mendelian randomization supported the effects of large TET2 CHIP against UAP. Large TET2 CHIP was linked to increased IL-1β levels, with IL-1β mediating the protection against UAP. CONCLUSIONS: CHIP protected against AP, with large TET2 CHIP specifically protecting against UAP. Elevated IL-1β levels might mediate this effect via plaque stabilization.