Clinical utility gains from incorporating comorbidity and geographic location information into risk estimation equations for atherosclerotic cardiovascular disease

Abstract

Objective: There are over 363 customized risk models of the American College of Cardiology and the American Heart Association (ACC/AHA) pooled cohort equations (PCE) in the literature, but their gains in clinical utility are rarely evaluated. We build new risk models for patients with specific comorbidities and geographic locations and evaluate whether performance improvements translate to gains in clinical utility.

Materials and methods: We retrain a baseline PCE using the ACC/AHA PCE variables and revise it to incorporate subject-level information of geographic location and 2 comorbidity conditions. We apply fixed effects, random effects, and extreme gradient boosting (XGB) models to handle the correlation and heterogeneity induced by locations. Models are trained using 2 464 522 claims records from Optum©'s Clinformatics® Data Mart and validated in the hold-out set (N = 1 056 224). We evaluate models' performance overall and across subgroups defined by the presence or absence of chronic kidney disease (CKD) or rheumatoid arthritis (RA) and geographic locations. We evaluate models' expected utility using net benefit and models' statistical properties using several discrimination and calibration metrics.

Results: The revised fixed effects and XGB models yielded improved discrimination, compared to baseline PCE, overall and in all comorbidity subgroups. XGB improved calibration for the subgroups with CKD or RA. However, the gains in net benefit are negligible, especially under low exchange rates.

Conclusions: Common approaches to revising risk calculators incorporating extra information or applying flexible models may enhance statistical performance; however, such improvement does not necessarily translate to higher clinical utility. Thus, we recommend future works to quantify the consequences of using risk calculators to guide clinical decisions.

Keywords: atherosclerotic cardiovascular disease; clinical utility; model calibration; net benefit; pooled cohort equations; subgroup performance.