Endothelial dysfunction in patients with systemic sclerosis.

INTRODUCTION: Patients with systemic sclerosis experience endothelial dysfunction and damage even in the absence of clinical manifestations. AIM: To evaluate various methods for assessing the endothelial function for their applicability to clinical practice. MATERIAL AND METHODS: Forty-two patients (7 men and 35 women) with systemic sclerosis and 36 controls (11 men and 25 women) matched for age, sex, body mass index, smoking habit, and comorbidities were enrolled in the study. We assessed each participant for typical risk factors for cardiovascular diseases and measured serum levels of vascular cell adhesion molecule-1 (VCAM-1) and thrombomodulin together with flow-mediated dilatation (FMD) of the brachial artery and intima-media thickness (IMT) of the common carotid artery using ultrasonography. RESULTS: Patients with systemic sclerosis did not differ from controls in serum levels of VCAM-1 and thrombomodulin, however, the statistical analysis with adjustment for potential confounders revealed increased levels of thrombomodulin in the patients (p = 0.03). They also had a 45% lower relative increase of FMD (FMD%), and 13% higher IMT (p < 0.01, both, also after adjustment for potential confounders). In a simple regression model, lower FMD% was determined by age (ß = -0.57, 95% confidence interval (CI): -0.72 to -0.43) and C-reactive protein levels (ß = -0.38, 95% CI: -0.55 to -0.22). Thicker IMT was related to age (ß = 0.64, 95% CI: 0.52-0.67), glomerular filtration rate (ß = -0.34, 95% CI: -0.5 to -0.18), and blood thrombomodulin levels (ß = 0.45, 95% CI: 0.13-0.76). CONCLUSIONS: Patients with systemic sclerosis present with endothelial dysfunction which may be detected using ultrasonographic methods. The exact mechanism of observed abnormalities is unknown, but it is possibly related to the chronic inflammation and ischemia-reperfusion injury.

Endothelial dysfunction in patients with granulomatosis with polyangiitis: a case-control study.

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 (ß = - 0.18 [95% CI: - 0.32 to - 0.04]), C-reactive protein (ß = - 0.17 [95% CI: - 0.27 to - 0.07]), IL-6 (ß = - 0.29 [95% CI: - 0.39 to - 0.19]), blood creatinine level (ß = - 0.2 [95% CI: - 0.3 to - 0.1]), and IMT (ß = - 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.

Endothelial dysfunction in patients with eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of vasculitis associated with asthma and eosinophilia. Endothelial dysfunction has been well documented in other types of vasculitis but not in EGPA. Thirty patients (10 men and 20 women) diagnosed with EGPA and remaining in a remission, and 58 controls (24 men and 34 women) matched for age, sex, and body mass index, were enrolled in the study. We assessed each participants for typical risk factors of cardiovascular diseases and measured serum levels of vascular cell adhesion molecule-1 (VCAM-1), interleukin 6 (IL-6), and thrombomodulin. We also measured flow-mediated dilatation (FMD) of the brachial artery and intima-media thickness (IMT) of the common carotid artery using ultrasonography. Patients with EGPA had 20% higher serum level of VCAM-1 (p < 0.001) and 41.9% of thrombomodulin (p < 0.001). They also had 38.8% lower relative increase of FMD (FMD%) (p < 0.001), indicating endothelial dysfunction. These differences remained significant also after adjustment for potential confounders. Laboratory and ultrasonographic parameters of endothelial injury were correlated to the markers of inflammation and impaired kidney function. Determinants of lower FMD% in a simple regression model were pack-years of smoking (ß = - 0.3 [95% confidence interval (CI) - 0.5 to - 0.1]), serum level of IL-6 (ß = - 0.36 [95% CI - 0.62 to - 0.1]), and thrombomodulin (ß = - 0.34 [95% CI - 0.6 to - 0.08]). EGPA patients are characterized by inflammatory endothelial injury that is likely related to the pathogenesis of the disease. Proper immunosuppressive treatment is the best method to prevent atherosclerosis and future cardiovascular events, the patients may also benefit from additional preventive interventions.