Abstract 11309: Lipoprotein(a) and the Pooled Cohort Equations for Risk Prediction: The Multi-Ethnic Study of Atherosclerosis

Introduction Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) but is not included in the ACC/AHA ASCVD Risk Estimator based on the Pooled Cohort Equations (PCE). Methods We evaluated the association between Lp(a) >50 mg/dL and risk for cardiovascular disease (CVD) events using multivariable Cox proportional hazards models stratified by ASCVD risk category in individuals free of baseline ASCVD with elevated Lp(a) in the Multi-Ethnic Study of Atherosclerosis (MESA). We then evaluated actual versus PCE-predicted risk by comparing 10-year CVD event rates in those with Lp(a) >50 mg/dL versus Lp(a) ≤50 mg/dL using Poisson regression with adjustment for the components of the PCE by strata of risk (<5%, 5-7.5%, 7.5-20%, ≥20%). We then evaluated the change in the C-index and continuous net reclassification improvement (NRI) with the addition of Lp(a) to the PCE. Results: In participants with borderline risk (5-7.5%), elevated Lp(a) was associated with greater risk for CVD events (HR 2.59, 95% CI 1.41, 4.78). Among patients with elevated Lp(a), the greatest discrimination of risk was present in those with borderline (5-7.5%) predicted risk, where the PCE significantly underestimated risk (observed rate: 8.9% for Lp(a) >50 mg/dL vs 4.1% for Lp(a)≤50 mg/dL, risk ratio 2.54, 95% CI 1.35-4.62, Figure ). In this group, addition of Lp(a) to the PCE resulted in C-index improvement of 0.063. The continuous NRI with the addition of Lp(a) for CVD was 0.0386 (95% CI -0.0115, 0.1087) overall, but 0.3142 (95% CI 0.0350, 0.6083) among those at borderline predicted risk. Conclusions: The PCE underestimates risk in individuals with borderline predicted risk and elevated Lp(a). The addition of Lp(a) to the PCE improves risk prediction in individuals with borderline risk, for whom the greatest opportunity to guide treatment decisions exists.