Cardiometabolic Composite Indices for Cardiovascular Risk Assessment in Diabetes: Information Overlap, Incremental Value, and Residual Risk Enrichment

Although cardiometabolic composite indices have shown associations with cardiovascular disease (CVD), it remains unclear whether they offer consistent risk information beyond that captured by established clinical predictors and their constituent variables. We aimed to determine whether 12 cardiometabolic composite indices provide cardiovascular risk information beyond conventional clinical factors and their individual components in adults with diabetes. The primary analyses included 1290 CHARLS participants with diabetes and no CVD at baseline, who were separated into development and fixed test sets; the principal findings were subsequently examined in an independent sample of 495 ELSA participants. Associations with incident CVD, information overlap, selection stability, model contribution, and incremental predictive performance were systematically assessed, followed by exploratory risk-stratified analyses. Estimated glucose disposal rate (eGDR) showed the most consistent risk signal. In CHARLS, each 1-standard-deviation increase in eGDR was associated with lower incident CVD risk (HR 0.65, 95% CI 0.56–0.75). Adding eGDR produced numerical increases in the C-index from 0.619 to 0.645 and the 9-year time-dependent AUC from 0.634 to 0.664, but paired bootstrap confidence intervals for these differences included zero, and eGDR did not clearly outperform its component variables. Among participants not classified as high risk, those with low eGDR comprised 36.4% of participants but accounted for 50.0% of subsequent CVD events; event proportions were 36.0% versus 20.6% (HR 1.84, 95% CI 1.12–3.04). In ELSA, higher eGDR was also associated with lower overall CVD risk, and similar numerical patterns in discrimination and residual-risk enrichment were observed, although the stroke-specific association was less clear. Overall, eGDR showed limited incremental discrimination, while exploratory risk-stratified analyses suggested possible residual-risk enrichment among participants with low eGDR; this finding requires prospective validation using prespecified thresholds.