Background: Granulomatosis with polyangiitis (GPA) is a rare granulomatous vasculitis affecting small- and medium-sized blood vessels. In optimally treated patients with long-standing disease, the common cause of death is atherosclerosis even in the absence of typical risk factors.
Objective: To evaluate endothelial dysfunction in GPA patients.
Methods: 44 patients (21 men and 23 women) diagnosed with GPA and 53 controls matched for age, sex, BMI and typical risk factors for cardiovascular diseases (22 men and 31 women) were enrolled in the study. We measured each participant's serum levels of vascular cell adhesion molecule-1 (VCAM-1), interleukin 6 (IL-6), and thrombomodulin. We also studied flow-mediated dilatation (FMD) of the brachial artery, intima-media thickness (IMT) of the common carotid artery and aortic stiffness using echocardiography.
Results: Patients with GPA showed a 15.9% increase in serum levels of VCAM-1 (p = 0.01), 66% of IL-6 (p < 0.001) and 50.9% of thrombomodulin (p < 0.001) compared to controls. FMD% was 48.9% lower in patients with GPA in comparison to controls (p < 0.001), after adjustment for potential confounders, with no differences regarding IMT or aortic stiffness. FMD% was negatively associated with duration of the disease (β = - 0.18 [95% CI: - 0.32 to - 0.04]), C-reactive protein (β = - 0.17 [95% CI: - 0.27 to - 0.07]), IL-6 (β = - 0.29 [95% CI: - 0.39 to - 0.19]), blood creatinine level (β = - 0.2 [95% CI: - 0.3 to - 0.1]), and IMT (β = - 0.14 (- 0.24 to - 0.04). In a multiple linear regression model, kidney function, IMT, pack-years of smoking, diabetes and level of VCAM-1 were independent predictors of lower FMD%.
Conclusion: GPA is characterized by endothelial dysfunction. FMD is a useful tool for the detection of endothelial injury.
Keywords: Atherosclerosis; Endothelium; Systemic vasculitis; Ultrasonography.