#3018 CARDIOVASCULAR DISEASE AND DETECTION OF CLONAL HEMATOPOIESIS OF INDETERMINATE POTENTIAL IN THE CHRONIC KIDNEY DISEASE POPULATION
Authors: Kislikova Maria , Lopez Maria Ana Batlle , Salinas Francisco Javier Freire , Blanco José Antonio Parra , Molina Maria Pilar García-Berbel , Fernández Alejandro Aguilera , Haces Vicente Celestino Piñera , Unzueta Maria Teresa Garcia , Hernandez Adalberto Benito , Millán Juan Carlos Ruiz San , Rodrigo Emilio 
Published: June 2023

Abstract

Background and Aims
Cardiovascular disease (CVD) is the main cause of morbidity and mortality in patients with chronic kidney disease (CKD). Novel determination of clonal expansion of hematopoietic stem cells carrying mutations in certain genes is called Clonal hematopoiesis of indeterminate potential (CHIP), it is well known the association with an increased risk of hematologic malignancies but in general population, CHIP has been associated with increased mortality and increased cardiovascular risk. The aim of our study was to analyze the influence of CHIP on the risk of CVD and heart disease in the population with CKD.

Method
128 patients with different degrees of CKD were roll in our prospective study in between September 1, 2020 and January 31, 2021. All of them have followed up in Nephrology clinics and any patient have previous cardiovascular pathology. For detection of silent heart disease was realized measurement of troponin I and NT-Pro-BNP in the blood using a microparticle chemiluminescence assay and the degree of coronary calcification was calculated by the computed tomography (CT): Agatston method. All the patients were prospectively followed up for 18 months, recording the occurrence of major cardiovascular events. For detection of CHIP massive sequencing was performed with Ion Chef System On-demand technology using Ion AmpliSeqTM Kit for Chef DL8. The data analysis was done with the Torrent SuiteTM software and Varsome software, following the criteria of the American College of Medical Genetics (ACMG).

Results
36.7% of the patients presented CHIP (pathogenic and probably pathogenic mutations) and 24.2% (only pathogenic mutations). TET2 was the most frequently affected gene (21.1%). The percentage of patients with CHIP MPL gene mutation was 12,5%, DNMT3 7%, JAK 1,6% and ASXL1 0,8%. 9 patients developed major cardiovascular events (MACE). Using univariate Cox regression analysis, the presence of MACE was related to global coronary calcification (OR 1.001, 95% CI 1.001-1.001, p = &lt; 0.001), NT-ProBNP (OR 1.090, 95% CI 1.050-1.132, p = &lt; 0.001) but there was no relation to smoking (OR 2.796, 95% CI 0.750-10.415, p = 0.125). Patients with CHIP did not have a higher risk of MACE, although patients with DNMT3A mutations did have a higher risk (HR 6.637, 95% CI 1.443-30.533, p = 0.015) independently of other variables. Using multivariate logistic regression analysis, the presence of CHIP was not related to coronary calcification (OR 0.387, 95% CI 0.142-1.058, p = 0.387), nor was it related to troponin I or NT-Pro-BNP.

Conclusion
The presence of CHIP was not associated with a greater risk of silent heart disease or cardiovascular events, although DNMT3a mutations, analyzed independently, were associated with a greater number of cardiovascular events in our CKD population.