Is cardiovascular risk profiling from UK Biobank retinal images using explicit deep learning estimates of traditional risk factors equivalent to actual risk measurements? A prospective cohort study design

Objective Despite extensive exploration of potential biomarkers of cardiovascular diseases (CVDs) derived from retinal images, it remains unclear how retinal images contribute to CVD risk profiling and how the results can inform lifestyle modifications. Therefore, we aimed to determine the performance of cardiovascular risk prediction model from retinal images via explicitly estimating 10 traditional CVD risk factors and compared with the model based on actual risk measurements. Design A prospective cohort study design. Setting The UK Biobank (UKBB), a prospective cohort study, following the health conditions including CVD outcomes of adults recruited between 2006 and 2010. Participants A subset of data from the UKBB which contains 52 297 entries with retinal images and 5-year cumulative incidence of major adverse cardiovascular events (MACE) was used. Our dataset is split into 3:1:1 as training set (n=31 403), validation set (n=10 420) and testing set (n=10 474). We developed a deep learning (DL) model to predict 5-year MACE using a two-stage DL neural network. Primary and secondary outcome measures We computed accuracy, area under the receiver operating characteristic curve (AUC) and compared variations in the risk prediction models combining CVD risk factors and retinal images. Results The first-stage DL model demonstrated that the 10 CVD risk factors can be estimated from a given retinal image with an accuracy ranging between 65.2% and 89.8% (overall AUC of 0.738 with 95% CI: 0.710 to 0.766). In MACE prediction, our model outperformed the traditional score-based models, with 8.2% higher AUC than Systematic COronary Risk Evaluation (SCORE), 3.5% for SCORE 2 and 7.1% for the Framingham Risk Score (with p value<0.05 for all three comparisons). Conclusions Our algorithm estimates the 5-year risk of MACE based on retinal images, while explicitly presenting which risk factors should be checked and intervened. This two-stage approach provides human interpretable information between stages, which helps clinicians gain insights into the screening process copiloting with the DL model.