Abstract 4357288: Comparative evaluation of a proteomic cardiovascular risk assessment tool to coronary artery calcium score

Background: Coronary artery calcium (CAC) scores are a powerful measure for assessing atherosclerotic cardiovascular disease (ASCVD) burden and guiding preventative treatments. However, CAC does not predict systemic risk of cardiovascular events, and many pharmacotherapies have broader health benefits beyond coronary event risk predicted by CAC. Hypothesis: The goal of this study was to determine whether a previously validated proteomic test for predicting a broad composite of four-year cardiovascular (CV) events could enhance the prognostic utility of CAC and potentially improve allocation of drugs that optimize metabolic health with broad benefits beyond the burden of ASCVD. Methods: We used a 27-plasma protein CV risk test (RCVR; a SomaScan TM derived proteomics risk score) to predict the four-year risk of a CV event (myocardial infarction, stroke, transient ischemic attack, heart failure hospitalization, death) in 2,122 participants from the Multi-Ethnic Study of Atherosclerosis observational cohort with elevated CV risk factors and compared predictive results to CAC Agatston scores. Discriminatory performance was assessed using C-Index and 4-year AUC. Cox Proportional Hazard (CoxPH) ratios were calculated for composite CV and ASCVD (myocardial infarction, resuscitated cardiac arrest, stroke, coronary heart disease death) outcomes and individual event types and compared using z-statistics. Changes in RCVR and CAC from baseline to visit 5 in CV event vs. event free participants were assessed using 2-tailed paired t-tests. CoxPH regression models of CV event status distributed by RCVR, CAC, and clinically relevant co-factors were evaluated for performance relative to individual models. Results: Both RCVR and CAC were strong predictors of 4-year CV risk, but compared to CAC, RCVR had a significantly higher C-index (0.68 (0.65-0.70) vs. 0.63 (0.60-0.65)) and CoxPH ratios for the CV composite outcome (p<0.001), all cause death (p<0.001) and heart failure (p=0.015). A combined CoxPH model of RCVR + CAC + AGE had a significantly higher 4-year AUC (0.72, p<0.05) and C-Index (0.71, p<0.05) than RCVR and CAC only models. Both the RCVR and CAC scores were sensitive to change in response to an adverse event, but RCVR was able to distinguish between event and event free participants with a CAC score of 0. Conclusion: Together, these results highlight the potential utility of prognostic protein testing as a novel, complementary tool for CV risk assessment.