Combined inflammatory, lipid-accumulation, and pulsatile hemodynamic burden and cardiovascular disease across adapted CKM stages: a CHARLS cohort study

Cardiovascular-kidney-metabolic (CKM) stages summarize disease progression but may conceal variation in biological burden and cardiovascular risk. We investigated whether a composite of C-reactive protein (CRP), lipid accumulation product (LAP), and pulse pressure (PP) was associated with incident cardiovascular disease (CVD) and absolute-risk gradients within adapted CKM stages. This prospective analysis included 7779 CHARLS participants aged 45 years or older without baseline CVD. CLP was calculated as the equal-weight sum of standardized ln(CRP + 1), ln(LAP), and PP. During a median follow-up of 9.0 years, 1911 CVD events occurred. Each 1-SD higher CLP was associated with higher CVD hazard after multivariable adjustment (hazard ratio, 1.22; 95% confidence interval, 1.16–1.28); the hazard ratio for quartile 4 versus quartile 1 was 1.85 (1.60–2.13). Nine-year cumulative incidence increased from 13.9% to 27.8% across CLP quartiles and from 16.2% to 29.8% within adapted stage 2. Relative associations did not differ significantly across stages (P for interaction = 0.147). Results were robust in competing-risk, selection-weighted, and alternative event-time analyses. CLP captured continuous multidomain burden and identified substantial absolute-risk heterogeneity within adapted CKM stages. These findings support epidemiologic characterization and require external validation before clinical use.