Abstract WMP100: Association Of Clonal Hematopoiesis Of Indeterminate Potential With Clinical Features And Outcome Of Patients With Acute Ischemic Stroke

Abstract

Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) has been linked with incident cardiovascular disease and its outcome. However, the association between CHIP and acute ischemic stroke is not yet fully elucidated. Methods: This retrospective, observational cohort study included 366 acute ischemic stroke patients from a single center prospective stroke registry and 4,628 general population control (age over 40 years old). We compared the prevalence of CHIP between stroke patients and control groups. A multivariable linear or logistic regression model was used to assess the association between CHIP and initial stroke severity, hemorrhagic transformation and functional disability at 90-day (modified Rankin scale score >1) after stroke. The contribution of individual CHIP driving genes was also evaluated. Results: When comparing the acute ischemic stroke patients (N=366) and the general population (N=4,628), the prevalence of CHIP was significantly higher in stroke patients than in the general population (32.0% vs. 13.9% with variant allele frequencies of 1.5%, p<0.001). Most mutated genes in CHIP of stroke patients were DNMT3A, TET2, and PP1MD, in order. In the stroke patients group, the presence of CHIP was significantly associated with initial stroke severity (β=1.4350, p=0.0453). Furthermore, after adjusting covariates, presence of CHIP independently predicted the occurrence of hemorrhagic transformation (adjusted odds ratio [aOR]=7.261, 95% confidence interval [CI] 4.183-12.968, p<0.001) and functional disability after stroke (aOR=2.214, 95% CI 1.237-3.984, p=0.008). PP1MD was most strongly associated with the incident ischemic stroke, while DNMT3A was most highly related with a functional disability after stroke. Conclusion: CHIP was obviously increased in ischemic stroke patients. Furthermore, CHIP was significantly associated with stroke severity, hemorrhagic transformation, and functional disability at 90 days.