Abstract 4146122: Potential Protective Roles of Clonal Hematopoiesis of Indeterminate Potential in Angina Pectoris

Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) poses strong relationship to the occurrence of cardiovascular diseases with the process of aging. IL-1β is associated with both CHIP and atherosclerotic lesions stabilization. However, potential protective effects of CHIP and IL-1β elevation in angina pectoris have been barely explored. Hypothesis: We hypothesis CHIP protects against angina pectoris via preventing atherosclerotic lesions rupture by the effect of IL-1β. Methods: In UK Biobank population with exome sequencing data, participants with any CHIP or large CHIP were defined as those with variant allele fraction (VAF) ≥ 2% or 10% respectively on any CHIP gene. Angina pectoris, stable angina pectoris and unstable angina pectoris was defined as main diagnosis of inpatient record in terms of ICD-10 code I20, I20.8 and I20.0, respectively. The effects of CHIP on angina pectoris were estimated in logistic regression models, including age, sex, and history of atherosclerotic heart disease as covariates. Propensity score matching (PSM) of 1:1 was applied for more stringent analysis. Proteomics analysis was carried out using linear regression model. Results: Total 465769 participants were included for final analysis (aged 56.5±8.1 years, 45.7% male) after excluding those with hematological malignancy. Covariate-adjusted models showed that large CHIP significantly protected against angina pectoris (OR=0.863, p=0.019), especially the unstable angina pectoris subtype (OR=0.931, p=0.028). Both any CHIP and large CHIP of specific genes manifested significantly protective effects on angina pectoris (OR any =0.104, p<0.001; OR large =0.017, p<0.001) and unstable angina pectoris subtype (OR any =0.123, p<0.001; OR large =0.033, p<0.001) after PSM. Proteomic analysis showed IL-1β was significantly elevated among serum cytokines in CHIP population and positively associated with large CHIP (p=0.007). Conclusion: CHIP posed protective effects against angina pectoris, especially the unstable subtype. The underlying mechanism may be attributed to the atherosclerotic lesions stabilization mediated by higher serum IL-1β level. These findings suggested the novel perspective for the complex roles of CHIP in cardiovascular disease.