Abstract
BACKGROUND: The remnant cholesterol inflammatory index (RCII) is a novel metric that combines remnant cholesterol and high-sensitivity C-reactive protein, reflecting the metabolic and inflammatory risk. This study investigates the association between RCII and long-term risks of all-cause and cause-specific mortality in middle-aged and elderly populations in the US and China. METHOD: We analyzed data from the National Health and Nutrition Examination Survey (NHANES) and the China Health and Retirement Longitudinal Study (CHARLS), including 7,565 and 12,932 participants aged 45 years and older, respectively. The participants were categorized into quartiles based on natural log-transformed RCII (lnRCII) values. Kaplan-Meier survival analysis, Cox proportional hazards models, restricted cubic splines (RCS) and mediation analysis were used to examine the relationship between lnRCII and mortality outcomes, adjusting for potential covariates. RESULT: The mean age of the participants was 59.90 ± 10.44 years (NHANES) and 58.64 ± 9.78 years (CHARLS), with 53.28% and 52.50% female, respectively. Kaplan-Meier survival analysis showed that higher lnRCII quartiles (≥ 0.79 in NHANES, ≥ -0.13 in CHARLS) were significantly associated with increased all-cause mortality risk (p < 0.001). Each standard deviation (SD) increase in lnRCII corresponded to a higher risk of all-cause mortality, and the hazard ratios (HRs) and 95% confidence interval (CI) were 1.29 (95% CI: 1.21-1.36) in NHANES and 1.26 (95% CI: 1.15-1.38) in CHARLS. In NHANES, lnRCII was also associated with elevated risks of cardiovascular mortality (HR = 1.21, 95% CI: 1.08-1.35) and cancer mortality (HR = 1.30, 95% CI: 1.09-1.55). RCS analysis indicated a J-shaped relationship between lnRCII and both all-cause and cardiovascular mortality, and a linear association with cancer mortality. Mediation analysis showed that systolic blood pressure and fasting plasma glucose partially mediated these associations. Subgroup analyses suggested a stronger association between lnRCII and all-cause mortality in middle-aged US participants (p for interaction = 0.010). CONCLUSIONS: Elevated RCII levels are significantly associated with increased all-cause mortality risk middle-aged and elderly populations in both the US and China. In the US population, RCII is also associated with increased risks of cardiovascular and cancer mortality. By integrating metabolic and inflammatory risk factors, RCII may serve as a valuable tool for mortality risk stratification and clinical decision-making.