Residual cholesterol inflammatory index and its prognostic role in mortality among individuals with cardiovascular–kidney–metabolic syndrome stages 0–3 based on U.S. and Chinese national cohorts

BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome, marked by multisystem dysfunction, is an emerging health concern. Traditional risk factors have limited ability to predict long-term mortality in CKM stages 0-3. The residual cholesterol inflammatory index (RCII), which integrates lipid abnormalities and chronic inflammation, may offer a novel prognostic tool. However, its independent value for predicting all-cause and cardiovascular mortality in early-stage CKM remains unclear. METHODS: This study analyzed data from the National Health and Nutrition Examination Survey (NHANES, 1999-2010), including 9,014 individuals at CKM stages 0-3. We assessed the relationship between RCII and all-cause and cardiovascular disease (CVD) mortality using weighted Cox models and restricted cubic splines. External validation was performed using the China Health and Retirement Longitudinal Study (CHARLS). Mediation analysis explored the role of estimated glucose disposal rate (eGDR), and machine learning models were developed to predict mortality risk. RESULTS: Over a median follow-up of 13.4 years, 1,450 all-cause deaths and 496 CVD deaths were observed. RCII was significantly associated with both mortality outcomes. For each 1-SD increase in RCII, the hazard ratios were 1.151 (HR = 1.151 [95% CI 1.090-1.215]) for all-cause mortality and 1.192 (HR = 1.192 [95% CI 1.041-1.364]) for CVD mortality. These results were consistent with the CHARLS data, where each 1-SD increase in RCII was associated with a hazard ratio of 1.152 (HR = 1.152 [95% CI 1.092-1.215]) for all-cause mortality. CONCLUSION: RCII is a strong predictor of mortality in CKM stages 0-3, potentially aiding risk assessment and early intervention.