Five lipid-inflammation composite indices and obesity-related metabolic disorders, cardiovascular and renal diseases A multi-state trajectory analysis using data from the UK Biobank cohort

BACKGROUND: Biomarkers that capture the dynamic transition from obesity to metabolic dysfunction and subsequent cardiorenal disease remain insufficient. This study evaluated stage-specific associations of lipid-inflammation indices across this continuum. METHODS: We included 109,442 obese adults (UK Biobank) across four stages, obesity (Stage 1), metabolic disorders (Stage 2), cardiorenal disease (Stage 3), and death (Stage 4). Five baseline indices (ApoB/A1-CRP, RCII, NHR, lymphocyte-to-HDL-C, monocyte-to-HDL-C) were evaluated. Markov multistate models were used to estimate transition-specific risks, with Cox regression and restricted cubic spline (RCS) analyses as complementary approaches. RESULTS: During a median follow-up of 15.73 years, 11.14% of participants progressed from Stage 1 to 2, and 25.88% from Stage 2 to 3. In fully adjusted model, ApoB/A1-CRP (HR, 1.07, 95% CI, 1.00-1.14, P = 0.048) and RCII (HR, 1.08, 95% CI, 1.01-1.15, P = 0.017) were significantly associated with Stage 2 to 3 progression. Upon Stage 3 stratification, NHR was primarily associated with mortality following cardiorenal disease onset. RCS analyses indicated significant non-linear associations for ApoB/A1-CRP, RCII, and NHR. RCII demonstrates robustness in sensitivity analysis. CONCLUSIONS: RCII is independently associated with the progression from metabolic disorders to cardiorenal diseases in obesity. It may serve as a clinically biomarker for early risk stratification.