Abstract 13915: Comparison of Proteomic CV Risk to Established ASCVD 10-year Risk Decision Points

Introduction: The ASCVD pooled cohort equation (PCE) is well-established for CV risk assessment. Decision points for determining treatment plans are low, intermediate and high risk over 10 years, however this approach over and underestimates risk in certain subgroups. The validated CV Risk SomaSignal® Test (SST) provides 4-year risk probability of MACE allowing for timely assessment of risk, but the shorter timescale makes comparison to 10-year PCE risk less intuitive. Hypothesis: Using a previously described metacohort (n=5,575) of patients with increased CV risk, we hypothesized that PCE would stratify patients differently than the CV Risk SST, and that CV Risk score scaled to 10 years would yield an improved net reclassification index (NRI). Methods: CV Risk SST and PCE scores were calculated on metacohort plasma samples. CV risk score was scaled to 10 years by parameterizing the model for a 10-year score, and then calculating a quadratic equation for the conversion. CV risk score was stratified by four established risk bins, whereas the PCE was stratified similarly using <7.5%, 7.5%-15%, 15%-20%, and > 20% risks based on literature and practice-derived cutoffs. Event rates were compared between scores, and NRI was calculated. Results: We observed total NRI of 11.4% for the 10-year CV Risk SST vs. PCE, with up-classification (positive NRI=83.7%) mitigating down-classification (negative NRI=-0.723). Event rates for the high-risk group in the CV Risk test were higher than the PCE, and lower in the low-risk group (p < 0.05). Conclusions: The CV Risk SST stratifies patients by identifying low- and high-risk groups using thresholds that are more discriminatory than low-risk and high-risk thresholds in the PCE. For comparison, the CV risk SST can be scaled to 10-year risk, with CV risk SST having a positive NRI for identifying MACE. This reclassification can allow targeted therapies in patients at greater risk and use of non-pharmacological therapies in the low-risk patients.