Validation and comparison of cardiovascular risk prediction equations in Chinese patients with Type 2 diabetes

Aims For patients with diabetes, the European guidelines updated the cardiovascular disease (CVD) risk prediction recommendations using diabetes-specific models with age-specific cut-offs, whereas American guidelines still advise models derived from the general population. We aimed to compare the performance of four cardiovascular risk models in diabetes populations.Methods and results Patients with diabetes from the CHERRY study, an electronic health records-based cohort study in China, were identified. Five-year CVD risk was calculated using original and recalibrated diabetes-specific models [Action in Diabetes and Vascular disease: PreterAx and diamicroN-MR Controlled Evaluation (ADVANCE) and the Hong Kong cardiovascular risk model (HK)] and general population-based models [Pooled Cohort Equations (PCE) and Prediction for Atherosclerotic cardiovascular disease Risk in China (China-PAR)]. During a median 5.8-year follow-up, 46 558 patients had 2605 CVD events. C-statistics were 0.711 [95% confidence interval: 0.693-0.729] for ADVANCE and 0.701 (0.683-0.719) for HK in men, and 0.742 (0.725-0.759) and 0.732 (0.718-0.747) in women. C-statistics were worse in two general population-based models. Recalibrated ADVANCE underestimated risk by 1.2% and 16.8% in men and women, whereas PCE underestimated risk by 41.9% and 24.2% in men and women. With the age-specific cut-offs, the overlap of the high-risk patients selected by every model pair ranged from only 22.6% to 51.2%. When utilizing the fixed cut-off at 5%, the recalibrated ADVANCE selected similar high-risk patients in men (7400) as compared to the age-specific cut-offs (7102), whereas age-specific cut-offs exhibited a reduction in the selection of high-risk patients in women (2646 under age-specific cut-offs vs. 3647 under fixed cut-off).Conclusion Diabetes-specific CVD risk prediction models showed better discrimination for patients with diabetes. High-risk patients selected by different models varied significantly. Age-specific cut-offs selected fewer patients at high CVD risk especially in women.Lay summary This large electronic health records-based real-world study indicated that the diabetes-specific cardiovascular risk models had better discriminative abilities than the models derived from the general population in Chinese patients with Type 2 diabetes. Current guidelines-recommended models, i.e. ADVANCE, PCE, and China-PAR, selected significantly different high-risk groups with various observed cardiovascular risks, indicating the potential considerable misclassification of risk stratification in clinical decision-making for preventive interventions.Compared with the fixed cut-off, the influence of the age-specific cut-offs for high risk of cardiovascular disease was different in men and women: age-specific cut-offs selected similar to 27% fewer high-risk patients in women but similar in men. Graphical Abstract Left panel: summary of the design and the four cardiovascular disease risk prediction models assessed in the study. Middle panel: C-index for the PCE, China-PAR, ADVANCE, and HK models in the study population. Right panel: overlap of high-cardiovascular disease-risk patients in the study population in the PCE-ADVANCE model pair in men and the China-PAR-ADVANCE model pair in women. ADA, American Diabetes Association; ADVANCE, Action in Diabetes and Vascular disease: PreterAx and diamicroN-MR Controlled Evaluation; China-PAR, Prediction for Atherosclerotic cardiovascular disease Risk in China; CVD, cardiovascular disease; ESC, European Society of Cardiology; HK, the Hong Kong cardiovascular risk model; PCE, Pooled Cohort Equations.