Abstract 13080: Clinical Significance of Clonal Hematopoiesis With JAK2V617F in Patients With Cardiovascular Diseases

Abstract

Background: It becomes increasingly clear that age-related clonal hematopoiesis (CH) is associated with cardiovascular diseases. However, CH with a driver mutation that causes myeloproliferative neoplasm (MPN) is not fully understood. Objective: To determine the clinical relevance of CH with MPN-driving mutations on cardiovascular diseases. Methods: This study prospectively enrolled 832 patients with cardiovascular diseases who did not show any hematological disorders. We examined the presence of the known MPN-driving mutations including JAK2V617F, CALRdel52, CALRins5, MPLW515L, and MPLW515K by an allele-specific polymerase chain reaction. Results: Out of 832 patients, 16 patients (1.9%) exhibited MPN-driving mutations including 15 patients with JAK2V617F (1.8%) and 1 patient with CALRins5 (0.1%). We divided the patients into two groups: vascular diseases including coronary artery disease, stroke, aortic aneurysm, aortic dissection, peripheral artery disease, deep vein thrombosis, and pulmonary thromboembolism (n=462, 55%) and non-vascular diseases (n=370, 45%). The prevalence of JAK2V617F-positive CH was significantly higher in patients with vascular diseases than in those with non-vascular diseases (2.8% vs. 0.5%, P = 0.014). In a multivariable analysis adjusted for known classic-atherosclerotic risk factors (age, male, obesity, smoking, hypertension, diabetes mellitus, dyslipidemia), the presence of JAK2V617F-positive CH was independently associated with vascular diseases (odds ratio, 5.448; P = 0.043). Additionally, peripheral leukocyte IL1B mRNA expressions as well as plasma interleukin-1β concentrations were significantly increased in patients with JAK2V617F-positive CH compared to those without JAK2V617F (P = 0.040 and P = 0.030, respectively). Conclusions: CH with JAK2V617F, but not CALR or MPL mutations, was significantly associated with vascular diseases independently on classic-atherosclerotic risk factors, in relation to interleukin-1β-related inflammatory mechanisms. JAK2V617F is a potential diagnostic and therapeutic target for vascular diseases.