# Association of Remnant Cholesterol Inflammatory Index with Stroke, Heart Disease and All-Cause Mortality Across Cardiovascular–Kidney–Metabolic Syndrome Stages 0–3: A National Cohort Study

## TL;DR

Higher levels of a cholesterol-inflammation index are linked to increased risks of stroke, heart disease, and death in people with cardiovascular-kidney-metabolic syndrome.

## Contribution

This study identifies RCII as a potential biomarker for predicting cardiovascular and mortality risks in early stages of CKM syndrome.

## Key findings

- Higher baseline RCII was associated with increased stroke and mortality risks.
- Cumulative RCII showed a stronger link to all-cause mortality.
- K-means clustering identified high RCII clusters with elevated heart disease and mortality risks.

## Abstract

Background: The Remnant Cholesterol Inflammatory index (RCII) has been proposed as a marker of insulin resistance and systemic inflammation. However, its associations with incident stroke, incident heart disease, and all-cause mortality among individuals with cardiovascular–kidney–metabolic (CKM) syndrome stages 0–3 remain uncertain. Methods: This longitudinal cohort study used data from the China Health and Retirement Longitudinal Study (CHARLS). The remnant cholesterol inflammatory index (RCII) was calculated as [RC (mg/dL) × hs-CRP (mg/L)]/10. Outcomes included incident stroke, incident heart disease, and all-cause mortality. Covariates were prespecified based on established risk factors. Cox proportional hazards models and restricted cubic spline (RCS) analyses were used to evaluate associations between RCII and each outcome. Long-term RCII patterns were identified using k-means clustering. Robustness was assessed using subgroup and sensitivity analyses. Results: The final study involved 6994 participants in the stroke and heart disease cohort and 7245 participants in the all-cause mortality cohort, all within CKM syndrome stages 0–3. Higher baseline RCII was associated with increased risks of stroke (HR = 1.55, 95% CI: 1.14–2.12) and all-cause mortality (HR = 1.67, 95% CI: 1.37–2.04) compared with the lowest quantile. Cumulative RCII showed a stronger association with all-cause mortality (HR for Q3 = 2.18, 95% CI: 1.54–3.11). RCS analysis suggested a J-shaped, non-linear association between cumulative RCII and all-cause mortality. (p for non-linearity < 0.05). K-means clustering further indicated that, relative to the reference group, cluster 2 (high-to-higher) had the highest risk of incident heart disease, whereas cluster 3 (high-to-moderate) had the highest risk of all-cause mortality. Conclusions: Higher RCII levels were associated with higher risks of stroke, heart disease, and all-cause mortality among individuals with CKM stages 0–3. RCII may serve as a promising biomarker for early risk stratification in clinic and prevention efforts in this population.