Abstract 15409: Analysis of Discrimination and Calibration of Two Cardiovascular Risk Scores in Patients With Non-Alcoholic Steatohepatitis Shows a Need for Improved Accuracy of These Models

Abstract

Background: CV risk can be estimated by risk scores such as the Framingham and the Pooled Cohort Equations (PCE). The applicability of these tools in present day NASH (non-alcoholic steatohepatitis) cohorts, individuals with increased morbidity and mortality from CVD, was evaluated to assess their relevance. Hypothesis: The Null Hypothesis is that there is no difference between the predicted CV risk as estimated by the Framingham or PCE risk scores, and the actual CV events that occur in a NAFLD (non-alcoholic fatty liver disease)/ NASH cohort. Aim: To assess the prognostic performance of the Framingham and PCE risk scores in a NAFLD/NASH cohort. Methods: The study population were US patients in the observational TARGET-NASH study with NAFLD/NASH aged 18 years or older. Patients with any CV history at or prior to index were excluded. Patients’ five-year CV risk was estimated using recalibrated Framingham and PCE models and compared with observed CV events. Model discrimination and calibration were assessed using the area under the receiver operator curve (AUROC) and Hosmer-Lemeshow test statistic, respectively. Results: 980 and 587 patients in the Framingham and PCE cohorts, respectively, had all data needed for calculation of CV risk, of which 274 and 169 had at least five years of follow-up. Framingham five-year predicted CV risk was significantly greater among patients who did vs did not experience a CV event (13.7% [SD 9.0] vs 10.5% [SD 8.8]; p=0.02). No statistically significant difference was observed in the PCE analysis. The AUROC was 0.62 (95% CI 0.51, 0.73) for Framingham and 0.58 (95% CI 0.44, 0.72) for PCE at five years, with worst predictive performance among the subgroup of cirrhotic NASH patients for both risk equations. Analyses of model calibration revealed a statistically significant lack of calibration for both tools at five years (Framingham: χ 2 =25.58, p=0.001; PCE: χ 2 =33.86, p<0.001). Conclusion: Framingham and PCE may have poor predictive accuracy for CVD risk in NAFLD/NASH cohorts. This tended to be most apparent among the upper decile of predicted risk, with predicted values far exceeding the observed. Lack of ten-year follow-up and unmeasured risk factors may also explain some of the residual overestimation not accounted for in our models.