Association of remnant cholesterol inflammatory index and hypertension with incident cardiovascular disease

Cardiovascular disease (CVD) is a leading cause of global mortality. The remnant cholesterol inflammatory index (RCII) is a composite risk marker for metabolic disorders involving atherogenic lipids and systemic inflammation. While the RCII has been shown to have prognostic value in conditions such as stroke, its independent longitudinal association with incident CVD and its joint impact with hypertension remain poorly understood. We included 6,659 participants from the China Health and Retirement Longitudinal Study (CHARLS). The RCII was calculated as [remnant cholesterol (mg/dL) × hs-CRP (mg/L)] / 10. Restricted cubic splines were applied to explore the dose-response relationship between continuous RCII and incident CVD. Cox proportional hazards models were utilized to evaluate the independent and joint associations of RCII and hypertension with incident CVD. Kaplan-Meier curves were used to visualize time-to-event trajectories, stratified by baseline hypertension status and RCII categories and across their joint subgroups. Incremental predictive value was evaluated via Harrell’s C-index, time-dependent area under the curve (AUC), calibration curves, and decision curve analysis (DCA). During 51,168 person-years of follow-up (median 7.68 years), 1,677 incident CVD events were recorded. Cox models showed that higher RCII quartiles were significantly associated with increased CVD risk, and restricted cubic splines revealed a nonlinear dose-response relationship for continuous RCII. Subgroup analyses identified significant age-related heterogeneity, with risk estimates being more pronounced in participants aged < 60 years. Regarding their joint impact, formal tests confirmed no multiplicative or additive synergy between RCII and hypertension. However, RCII and hypertension independently compounded the CVD burden. Individuals with high RCII (> median) and hypertension exhibited the highest CVD risk (HR: 1.62, 95% CI: 1.41–1.87), compared to the reference group (low RCII and no hypertension). Finally, incorporating both metrics into baseline risk models significantly improved prognostic discrimination, as evidenced by higher Harrell’s C-index and time-dependent AUC values. The RCII is an independent risk marker for incident CVD that exerts a profound cumulative risk burden when co-occurring with hypertension. Additionally, significant age heterogeneity was observed in this study.