Association of high remnant cholesterol inflammatory index reversal with subsequent cardiovascular disease in middle-aged and older Chinese adults: a 2015-wave landmark cohort analysis of CHARLS

The remnant cholesterol inflammatory index (RCII) integrates remnant cholesterol and high-sensitivity C-reactive protein (hsCRP), but the prognostic relevance of longitudinal RCII change remains uncertain. We conducted a 2015-wave landmark cohort analysis of the China Health and Retirement Longitudinal Study. Participants aged 45 years or older whose 2011 RCII met a study-specific high-RCII definition (sample-derived 75th percentile) entered the post-landmark analysis only if they remained alive, cardiovascular disease (CVD)-free, observable, and trajectory-evaluable through the 2015 wave. Reversal was RCII below the fixed 2011 threshold at the 2015 wave; persistent high RCII was the reference. Incident CVD was ascertained through the 2020 wave. Missing covariates were multiply imputed (60 data sets). Associations were estimated using modified Poisson regression, inverse-probability weighting (IPTW), augmented inverse-probability weighting (AIPW), and sensitivity analyses. Among 1,221 participants, 791 had persistent high RCII and 430 had reversal; CVD occurred in 189 (23.9%) and 70 (16.3%), respectively. Fully adjusted modified Poisson regression showed lower subsequent CVD risk with reversal (risk ratio [RR] 0.75, 95% confidence interval [CI] 0.58–0.97; P = 0.029). IPTW yielded standardized risks of 23.2% versus 17.7% (risk difference − 5.5% points, 95% CI -10.6 to -0.4), and AIPW yielded 23.2% versus 17.4% (risk difference − 5.8% points, 95% CI -10.9 to -0.7). Estimates were similar after excluding extreme hsCRP values, omitting physical activity, and adjusting for updated 2015 covariates. The alternative 90th-percentile definition did not reproduce the primary association (RR 1.09, 95% CI 0.77–1.54). Within this selected landmark cohort and under the study-specific 75th-percentile definition, observed RCII reversal was associated with lower subsequent CVD risk. This threshold-dependent finding should be regarded as an exploratory conditional observational association; it does not estimate an RCII-lowering intervention effect and should not be generalized directly to all Chinese middle-aged and older adults, all individuals with high baseline RCII, or alternative definitions of high RCII.