Abstract
INTRODUCTION: Remnant cholesterol (RC) and high-sensitivity C-reactive protein (hs-CRP) are established stroke risk factors, but their joint impact remains unclear. OBJECTIVES: This study aimed to evaluate the predictive value of the remnant cholesterol inflammatory index (RCII), a novel index integrating RC and hs-CRP, in assessing stroke risk. METHODS: We analyzed 9,898 participants aged 45 years or older, with no history of stroke at baseline, from the China Health and Retirement Longitudinal Study (CHARLS). RCII was calculated using the formula: RCII = RC (mg/dL) × hs-CRP(mg/L)/10. A subset of 5,704 participants was studied to investigate the relationship between cumulative RCII exposure and stroke incidence. The associations of both baseline and cumulative RCII with stroke risk were assessed using Cox proportional hazards regression model. RESULTS: During a median 7-year follow-up, 560 participants (5.7 %) experienced an incident stroke. Stroke incidence escalated with increasing RCII quartiles, from 3.5 % (Q1) to 7.6 % (Q4). In multivariable-adjusted analyses, each standard deviation increase in RCII was significantly associated with a 10.6 % increased risk of stroke (HR = 1.106, 95 % CI: 1.048-1.167). ROC analysis revealed that RCII had the highest AUC at 0.581, higher than RC (0.566) and hs-CRP (0.560), though the difference with RC was not statistically significant (P = 0.166). Mediation analysis indicated a reciprocal mediation between RC and hs-CRP on stroke risk. In a 3-year subset analysis, 288 participants suffered a stroke. Participants with cumulative RCII levels exceeding 36.14 had a significantly increased risk of incident stroke (HR = 1.462, 95 % CI: 1.102-1.939). Subgroup analyses showed a significant positive association between elevated RCII levels and stroke risk in males, but not in females. CONCLUSIONS: Elevated levels of RCII, both at baseline and cumulative, are significantly associated with an increased risk of stroke. Early intervention in patients with high RCII may further help reduce stroke risk.