Kidney function decline mediates the adverse effects of arterial stiffness on all-cause and cardiovascular disease mortality in Cardiovascular-Kidney-Metabolic syndrome population: A cohort study

AIDS: Cardiovascular-Kidney-Metabolic (CKM) syndrome links metabolic, renal, and cardiovascular disorders. The prognostic value and mechanisms of estimated pulse wave velocity (ePWV) in CKM syndrome remain unclear. METHODS: We analyzed 34,004 CKM syndrome patients from NHANES 1999-2018. Cox regression, restricted cubic splines, and mediation analyses examined ePWV-mortality associations and renal function's mediating role. RESULTS: Over 104 months median follow-up, 4,141 all-cause and 1,261 cardiovascular deaths occurred. In fully adjusted model, each unit ePWV increase associated with 32 % higher all-cause mortality (HR: 1.32, 95 % CI: 1.29-1.35) and 34 % higher CVD mortality (HR: 1.34, 95 % CI: 1.28-1.40). The association showed L-shaped patterns in non-advanced CKM cases and linear relationships in advanced stages. Kidney function decline mediated 24 % of all-cause and 26 % of CVD mortality risk. CONCLUSIONS: Elevated ePWV predicts increased mortality in CKM syndrome patients, with kidney function decline as a significant mediating pathway. These findings highlight the importance of arterial stiffness assessment and renal protection in CKM management.