Cumulative Vascular Burden: The Prognostic Value of a Time-Weighted Cardio-Ankle Vascular Index in Haemodialysis...

Chronic kidney disease and end-stage renal disease are burdened by extremely high cardiovascular mortality. The Cardio-Ankle Vascular Index (CAVI) is a blood-pressure-independent marker of arterial stiffness, but a single measurement may not reflect the time-dependent nature of vascular remodelling in haemodialysis. We hypothesized that a time-weighted CAVI (twCAVI), integrating arterial stiffness with dialysis vintage, would better predict all-cause mortality.

In this observational cohort study, 94 maintenance haemodialysis patients were followed from February 2016 to December 2024. Arterial stiffness was assessed by CAVI, and twCAVI was defined as mean CAVI × dialysis vintage (months). After preprocessing and feature selection, the association between arterial stiffness and overall survival over approximately 8 years was examined using a Cox proportional hazards model. Internal validity was assessed by 1,000 bootstrap iterations and expressed via Harrell's concordance index (C-index) and time-dependent area under the curve (AUC).

The final model retained six predictors: sex, vascular access, creatinine, alkaline phosphatase (ALP), ferritin, and twCAVI. In the multivariate model, male sex (HR 2.56, p = 0.0018), ALP (HR 1.01, p = 0.0082), ferritin (HR 1.002, p = 0.0067) and twCAVI (HR 1.0021, p = 0.0464) were independently associated with higher mortality, while higher creatinine was protective (HR 0.87, p = 0.0445). Central venous catheter use showed a borderline trend towards increased risk compared with arteriovenous fistula (HR 1.68, p = 0.0509). Bootstrap validation yielded a median C-index of 0.75 (95% confidence interval [CI] 0.68-0.83), with time-dependent AUCs generally ≥0.80 up to 102 months. Notably, exploratory survival analyses revealed an age-dependent inverse association between phosphorus levels and mortality, supporting the reverse epidemiology hypothesis in the elderly.

twCAVI, capturing the cumulative vascular burden risk, is a predictor of mortality in haemodialysis patients and improves long-term risk discrimination. A proof-of-concept web-based calculator was developed to facilitate the educational exploration of this metric.