Abstract 4366580: Using a proteomics-based test to assess cardiovascular risk in individuals with clonal hematopoiesis of indeterminate potential (CHIP)

Background: Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related phenomenon associated with increased cardiovascular (CV) risk, independent of traditional risk factors, which can make risk stratification a challenge. The residual cardiovascular risk (RCVR) test is a recently developed 27-protein model that has been shown to predict 4-year risk of a CV event (myocardial infarction, stroke, transient ischemic attack, heart failure hospitalization, death) in independent replication cohorts of at-risk populations. Objectives: The goal of this analysis was to evaluate whether the RCVR test could detect significant differences in CV risk between CHIP+ and CHIP- sub-populations using data from the CANTOS trial (NCT01327846), a study that enrolled subjects with a history of cardiovascular disease that were evaluated for their CHIP status. Methods: RCVR test scores were generated from SomaScan v4.1 assay data on EDTA plasma samples from the CANTOS trial. Baseline analysis compared mean RCVR test scores in CHIP+ (n=174) and CHIP- (n=1794) subjects who were either randomized into the placebo or canakinumab treated arms. A linear model of RCVR distributed by CHIP status, with fixed effects of treatment arm, age, and sex was evaluated in a Type III ANOVA to determine covariate adjusted between group differences in RCVR test scores. Results: The mean predicted RCVR test score was 4.96% greater at baseline for CHIP+ subjects compared to CHIP- subjects after adjusting for covariates (p=2.07e-3). Conclusions: The RCVR test predicted that the absolute risk of a cardiovascular event within four years is significantly greater for CHIP+ individuals. These results suggest RCVR may be able to capture the increased CV risk conferred by novel risk factors like CHIP status and highlight the potential utility of multi-protein-based prognostic test as a tool for CV risk assessment. Further analysis of longitudinal time points from the placebo arm of the trial are planned to assess whether cardiovascular risk increases at a different rate in CHIP+ and CHIP- individuals over time.