The remnant cholesterol inflammatory index and risk of future cardiovascular disease in early CKM syndrome: findings from CHARLS

BACKGROUND: Remnant cholesterol and systemic inflammation are two key, interrelated pathways in atherosclerosis. We examined whether the remnant cholesterol inflammatory index (RCII; remnant cholesterol × C-reactive protein/10) predicts incident cardiovascular disease (CVD) among adults in early cardiovascular-kidney-metabolic (CKM) stages. METHODS: We analyzed 5,961 China Health and Retirement Longitudinal Study participants aged ≥ 45 years (baseline 2015; follow-up through 2020) classified as CKM stages 0-3 and free of baseline CVD. Incident CVD (heart disease or stroke) was identified from self-reported physician diagnoses. We used multivariable Cox models with hierarchical adjustment, assessed dose-response patterns using restricted cubic splines, and conducted prespecified subgroup and exploratory mediation analyses. RESULTS: Over a median follow-up of 5.00 years (IQR, 5.00-5.09), 1,080 incident CVD occurred (18.1%). Each 1-unit increase in log-RCII was associated with higher CVD risk in the fully adjusted model (hazard ratio [HR] 1.070, 95% CI 1.016-1.127; P = 0.010). Compared with quartile 1, quartile 4 had increased risk (HR 1.239, 95% CI 1.029-1.492; P = 0.024; P for trend = 0.043). The dose-response association was linear (P for nonlinearity = 0.795), and no effect modification was detected (all P for interaction > 0.05). Systolic blood pressure mediated 5.0% (95% CI 1.10% to 17.00%) of the RCII-CVD association. CONCLUSIONS: Higher RCII was modestly associated with incident CVD across early CKM stages, suggesting a simple research marker to identify individuals at higher risk during a prevention window. Standardized thresholds and external validation of incremental predictive value are needed before clinical use.