Refined selection of individuals for preventive cardiovascular disease treatment with a transformer-based risk model
Authors: Rao S , Li Y , Mamouei M , Salimi-Khorshidi G , Wamil M , Nazarzadeh M , Yau C , Collins G , Vickers A , Danaei G , Rahimi K 
Published: October 2024

Abstract

Background
Although statistical models have been commonly used to identify patients at risk of cardiovascular disease (CVD) for preventive therapy, these models tend to over-recommend therapy [1]. Moreover, in populations with pre-existing diseases, the current approach is to indiscriminately treat all individuals, as modelling in this context is currently inadequate.

Aims
To develop and validate a novel deep learning model, the Transformer-based Risk assessment survival model (TRisk) model, for prediction of 10-year risk of CVD in both the general population and individuals with diabetes.

Methods
An open cohort of 3 million adults aged 25 to 84 years free of CVD and statin use was identified using linked primary and secondary electronic health records from 291 and 98 general practices in England, which were used for TRisk model development and external validation, respectively. Comparison against two commonly recommended statistical models (QRISK3 [2] and SCORE2 [3]) and a deep learning derivation of QRISK3 was conducted. Additional analyses compared discriminatory performance in other age groups, by sex, and across categories of socioeconomic status. Similar analyses were conducted in a subgroup of 59 thousand patients with diabetes.

Results
TRisk demonstrated superior discrimination (C index in the general population: 0.910; 95% confidence interval [CI]: 0.906 to 0.913). TRisk’s performance was found to be less sensitive to population age range than the benchmark models and outperformed other models also in all stratified analyses. All models were overall well-calibrated. In decision curve analyses, TRisk demonstrated greater net benefit than benchmark models across the range of relevant thresholds. In impact analyses, at the widely recommended 10% risk threshold and the higher 15% threshold for the general population, TRisk reduced both the total number of patients classified at high risk (by 27% and 39% respectively) and the number of false negatives as compared with currently recommended strategies. TRisk similarly outperformed other models in patients with diabetes. Compared with the widely recommended treat-all policy approach for patients with diabetes, TRisk at a 10% risk threshold would lead to deselection of 24% of individuals with a small fraction of false negatives (0.2% of cohort).

Conclusion
TRisk enabled a more targeted selection of individuals at risk of CVD compared to benchmark statistical and deep learning models, in both the general population and patients with diabetes. Incorporation of TRisk into routine clinical care would allow a reduction in the number of treatment-eligible patients in general population and subgroup with diabetes by approximately one-third and one-quarter respectively while preventing at least as many events as with currently adopted approaches.Models' discrimination on both cohortsImpact analyses for both cohorts