Arterial stiffness is related to cardiovascular risk in pseudoxanthoma elasticum

Background Pseudoxanthoma elasticum (PXE) is a rare, inherited disease with increased cardiovascular risk caused by arterial calcifications. Pathogenic genetic variants in the ABCC6 gene cause ectopic calcifications in Bruch’s membrane of the retina, skin, and arteries and are related to peripheral artery disease and cerebrovascular disease. The association between arterial stiffness and cardiovascular events in PXE is not yet well established. Purpose PXE is a rare disease starting at a young age with a relatively slow progression of arterial calcifications eventually leading to cardiovascular complications. This makes it challenging to assess cardiovascular risks and underlines the need for more intermediate endpoints to improve cardiovascular risk assessment. This study aims to determine the relationship between arterial stiffness and the occurrence of cardiovascular events in a nationwide PXE cohort. Methods A prospective cohort study was conducted in a nationwide PXE cohort. At the baseline visit, patients underwent extensive arterial stiffness measurements, including carotid-femoral pulse wave velocity (cfPWV) and the augmentation index (AIx) by pulse wave analysis (PWA). The outcome is the occurrence of cardiovascular events during follow-up, which is a composite score of cardiovascular death, cerebrovascular events, coronary events, and peripheral arterial interventions. Cox-proportional hazard models, adjusted for confounders, were used to calculate hazard ratios (HRs) and corresponding 95% confidence intervals for the relationship between arterial stiffness and the occurrence of cardiovascular events. Results A total of 390 patients were included in this study, with a mean age of 51±15 years, of whom 60% were women. During follow-up (median follow-up duration 6.1 years [IQR 3.1;9.2], 2392 person-years) 45 events occurred. This results in an incidence rate of 1.9 cardiovascular events per 100 person-years. Cerebrovascular events were the most frequently observed (N=32, 71%). A significant relation was found between a 1 m/s higher cfPWV and cardiovascular events (HR for a patient with a mean age of 51 years: 1.24 (95% CI 1.03-1.48) (Table 1). The effect of cfPWV significantly depends on age (p-value = 0.03). The HR for cardiovascular events decreases with increasing age (HR age of 30 years 1.67 (95%CI: 1.09;2.56) to HR age of 60 years 1.09 (95%CI 0.97-1.23)). A significant relation between a 10% higher AIx at baseline and future cardiovascular events was found (HR 1.37 (95%CI 1.03-1.83) (Table 1). There was no relationship between the AIx and age. Conclusion Increased arterial stiffness is independently related to a higher risk of cardiovascular events in PXE patients. In younger patients, the effect of the cfPWV is even more pronounced. Arterial stiffness, measured by cfPWV and AIx, may serve as an intermediate endpoint for assessing the risk of cardiovascular events in clinical trials evaluating preventive treatment in PXE.