Arterial stiffness is related to a higher risk of cardiovascular events in patients with pseudoxanthoma elasticum (PXE)

Background: Pseudoxanthoma elasticum (PXE) is a rare disease caused by pathogenic ABCC6 variants, leading to arterial calcifications and increased cardiovascular risk. Validated intermediate endpoints are needed to evaluate cardiovascular risk-reducing therapies in PXE. This prospective cohort study investigates the relationship between arterial stiffness and cardiovascular events in patients with PXE. Methods: This prospective cohort study obtained patients from the Dutch University Medical Center Utrecht Expertise Center for PXE. Arterial stiffness was measured with carotid-femoral pulse wave velocity (cfPWV) and the augmentation index (AIx). Cardiovascular endpoints were cardiovascular death, cerebrovascular and coronary events, and peripheral artery interventions. Cox proportional hazard models analyzed associations between arterial stiffness and cardiovascular events, adjusting for confounders. Results: Among 390 patients (mean age 51 ± 15 years, 60% women), 45 cardiovascular events occurred during a median follow up of 6.1 years (IQR 3.2; 9.2). A 1-m/s higher cfPWV was related to an increased risk of cardiovascular events (hazard ratio HR: 1.28; 95% CI 1.06–1.53). The effect of cfPWV depends on age ( p -value = 0.03), with a lower cardiovascular risk HR at older age (HR age at 40 years: 1.51; 95% CI 1.11–1.97 to HR age at 60 years: 1.12; 95% CI 1.00–1.26). A 10% higher AIx at baseline was related to future cardiovascular events (HR 1.46; 95% CI 1.10–1.95). No significant interaction between the AIx and age was found. Conclusion: This prospective cohort study shows that arterial stiffness, measured by cfPWV and AIx, is independently associated with increased cardiovascular risk in PXE. Measures of arterial stiffness could be explored as intermediate endpoints in trials evaluating cardiovascular risk-reducing therapies in PXE.