Joint association of atherogenic index of plasma and estimated glucose disposal rate with new-onset cardiovascular disease risk in individuals with cardiovascular–kidney–metabolic syndrome stages 0–3: a 9-year nationwide prospective cohort study

BACKGROUND: The atherogenic index of plasma (AIP) and estimated glucose disposal rate (eGDR) are two composite indices derived from routine metabolic measurements and are associated with cardiocerebrovascular disease risk. In individuals with Cardiovascular-Kidney-Metabolic (CKM) syndrome stages 0-3, however, it remains unclear whether joint stratification by these markers helps summarize gradients of cardiovascular disease, heart disease, and stroke risk beyond single-marker assessment. METHODS: Using data from the China Health and Retirement Longitudinal Study (CHARLS), 5,925 participants without CVD at the start and in CKM stages 0-3 were analyzed. Participants were grouped by median AIP and/or eGDR values. Kaplan-Meier curves and Cox models assessed the link between these indicators and new CVD, heart disease, and stroke cases. Furthermore, both multiplicative and additive interactions between AIP and eGDR were assessed. The predictive value was assessed using the time-dependent Harrell's C index, integrated discrimination improvement (IDI), and net reclassification improvement (NRI). RESULTS: A cohort of 5,925 participants aged 45 years and older (mean age: 57.92 ± 8.52 years) was analyzed, with 54.65% of the cohort being female. During the nine-year follow-up period, 1,467 (24.76%) participants developed incident CVD, including 1,106 (18.67%) with heart disease and 525 (8.86%) with stroke. The high AIP and low eGDR group had the highest risk, with CVD hazard ratios (HRs) of 1.35 (95% CI 1.14-1.59), heart disease HRs of 1.32 (95% CI 1.08-1.62), and stroke HRs of 1.59 (95% CI 1.19-2.12), using the low AIP and high eGDR group as the reference. Neither multiplicative nor additive interaction was statistically significant. The combined application of AIP and eGDR provided a modest improvement in predictive capability for cardiovascular disease, heart disease, and stroke. CONCLUSION: In individuals with CKM stages 0-3, combined AIP and eGDR stratification captured gradients of cardiovascular risk. The combined application of these indicators may provide modest incremental value for risk stratification within CKM stages, thereby aiding in the identification of high-risk individuals during the early stages of CKM.