Both Small and Large Non-aneurysmal Distal Aortic Diameters Are Associated with Limb Events in Patients with Established Cardiovascular Disease

OBJECTIVE: This prospective cohort study hypothesised that a small distal aortic diameter is associated with adverse arterial physiology and when co-existing with atherosclerosis leads to limb events. This study evaluated the relationship between distal aortic diameter and major adverse limb events (MALE), major adverse cardiovascular events (MACE), MALE and minor events, and mortality in patients with established cardiovascular disease. METHODS: Patients were included from the Utrecht Cardiovascular Cohort-Second Manifestations of ARTerial disease cohort. The outer-outer aortic diameter was measured with ultrasound, and diameters > 3 cm were excluded. The relationship between distal aortic diameter and MALE, MACE, and all cause mortality was reported by quintile, and stratified by sex. The continuous, unbinned values were evaluated using sex stratified multivariable Cox proportional hazard models with restricted cubic splines. RESULTS: The study included 8 463 patients (72% men, mean age 60.1 years, aortic diameter range 0.70 - 2.98 cm). In total, 809 major and minor limb events, 571 MALE, 1 731 MACE, and 2 213 deaths occurred (median follow up 10.1 years (interquartile range 5.3, 15.0 years). For men, a U shaped relationship between distal aortic diameter and major and minor lower limb events (lowest quintile hazard ratio (HR) 1.41, 95% confidence interval (CI) 1.09 - 1.83), and MALE (lowest quintile HR 1.39, 95% CI 1.04 - 1.87) was observed. For women, the lower quintile of aortic diameter was associated with major and minor limb events (HR 1.56, 95% CI 1.04 - 2.34), but not MALE (HR 1.11, 95% CI 0.69 - 1.78). The highest quintile was associated with all cause mortality (HR 1.64, 95% CI 1.27 - 2.12), MACE (HR 1.48, 95% CI 1.08 - 2.01), and vascular death (HR 1.71, 95% CI 1.16 - 2.53). results CONCLUSION: Non-aneurysmal distal aortic diameters are associated with major and minor limb events, MALE, and mortality in patients with established vascular disease, with differences between men and women. The relationship between aortic diameter and limb events is U shaped for men, meaning that both a large diameter and a small diameter are associated with increased risk of events.