Aortic Stiffness as a Mediator Between Chronic Kidney Disease and Heart Failure

Abstract

Introduction: Chronic kidney disease (CKD) markedly increases heart failure (HF) risk, but the mechanisms are incompletely understood. Aortic stiffness, measured by carotid-femoral pulse wave velocity (cfPWV), may be a key mediator.
Methods: A systematic review and mediation analysis framework applied to prospective cohort studies. Inclusion: adults with CKD stages 2–4, baseline cfPWV measurement, and HF hospitalization as outcome. Exclusion: prevalent HF, dialysis. Searched Embase and Medline (2000–2023).
Results: 12 studies (n=21,450 CKD patients) met criteria. Mean cfPWV was 11.2 m/s in CKD vs. 8.5 m/s in controls. In adjusted models, each 1 m/s increase in cfPWV was associated with 18% higher HF risk (HR 1.18, 95%CI 1.10–1.27). Formal mediation analysis (using change-in-coefficient method) showed aortic stiffness explained 34% (95%CI 22–46%) of the association between eGFR (per 10 ml/min/1.73m² decrease) and incident HF. Other mediators (BP, LV mass) accounted for additional 15%.
Discussion: CKD accelerates aortic stiffening through advanced glycation end-products, vascular calcification, and oxidative stress. Increased afterload leads to left ventricular hypertrophy and diastolic dysfunction. Limitations include lack of serial cfPWV measurements and possible reverse causation.
Conclusions: Aortic stiffness substantially mediates the CKD-HF link, suggesting that therapies targeting vascular compliance (e.g., mineralocorticoid receptor antagonists, exercise) may reduce HF burden in CKD.