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Title:
Endothelial dysfunction in systemie connective tissue diseases
Author:
Subject:
FMD ; vasculitis ; IMT ; endothelium ; systemie sclerosis
Abstract:
Introduction: The exact mechanism by which atherosclerosis is promoted in the connective tissue diseases remains unclear. The classical atherosclerotic risk factors do not seem to be present in these patients frequently enough to explain such an early manifestation of cardiovascular diseases. Aim: The aim of the study was to assess endothelial function in patients with selected systemic connective tissue diseases: granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), systemic sclerosis. Methods: The case group constituted 44 patients with GPA, 30 patients with EGPA and 42 patients with systemic sclerosis. The control group consist of 58 individuals (matched to patients by gender, age, BMI, and comorbidities). Every participant were assessed for the concentration of laboratory parameters of endothelial injury: vascular cell adhesion molecule (VCAM-1), and soluble thrombomodulin levels. Additionally every patient had a measurement of flow-mediated dilatation of the brachial artery (FMD%), intima-media thickness of the carotid artery (IMT) and aortic stiffness (in GPA patients). Results: GPA patients had 15.9% higher VCAM-1 concentration (p=0.01) and 50.9% higher thrombomodulin (p<0.001). Patients with EGPA had a 20% higher serum level of VCAM-1 and a 42% of thrombomodulin compared to healthy individuals (both p<0.001). Patients with systemi ; c sclerosis had similar serum levels of VCAM-1 and thrombomodulin as compared to healthy individuals, however, the ANCOVA analysis revealed that levels of thrombomodulin were increased in the systemic sclerosis group (p=0.03). In ultrasonograpy, GPA patients had 48.9% decrease in FMD% (p<0.001) and similar IMT and aortic stiffness. The EGPA group was characterized by a 38.8% decrease in FMD% (p<0.001) without any statistical differences in IMT. Patients with systemic sclerosis were characterized by 45% lower FMD% and 13% higher IMT, as compared to the control group (p<0.01).The values of FMD%, IMT, VCAM-1 and thrombomodulin were mainly associated with CRP, IL-6, creatinine and urea concentrations. Conclusions: The patients with evaluated connective tissue diseases present with endothelial injury which is the result of chronic inflammation process, an influence of antibodies and organ damages as a consequence of the disease.