Lower modified rodnan skin score values and complement 4 levels are associated with arterial endothelial dysfunction in patients with systemic sclerosis

Abstract

Abstract Background Systemic sclerosis (SSc) is a multisystem autoimmune disease affecting skin and multiple organs. Although immunopathological evidence supports direct arterial involvement leading to tissue ischemia in SSc, factors associated with arterial involvement are not precisely determined due to the rarity of SSc. In this study, we aimed to investigate aortic stiffness and endothelial functions in patients with SSc. Methods Patients under treatment of our Rheumatology department and healthy controls have been included in our study. Aortic stiffness was examined by pulse wave velocity (PWV) exam and endothelial functions were assessed by flow mediated dilation (FMD). Individuals with known atherosclerotic risk factors were excluded from our study. A thorough biochemical examination of all individuals and immunologic markers of patients with SSc was completed. All of the organ involvements in patients with SSc were noted and modified Rodnan skin score (MRSS) was calculated. Results A total of 61 patients and 75 healthy controls were included in our study. Brachial-ankle PWV values were significantly higher (6.89±0.93 vs 6.49±0.22 m/sec; p:0.001) and brachial FMD values were significantly lower (16.7±6.7 % vs 18.7±3.8 %; p: 0.03) in patients with SSc. We have also grouped individuals according to severe FMD impairment (FMD < 10%). None of the healthy controls had severe impairment whereas 15 patients with SSc had FMD values lower than 10%. Higher anti-smooth muscle (Sm) antibody positiveness (40 % vs 15.4 %), lower complement 4 levels (23.6±16.7 vs 31.1±11.1 mg/dL), higher plasma iron values (70.3±43.6 vs 31.4±45.2 mcg/dL) and lower MRSS values (11.4±4.8 vs 20.7±10.9) were observed in SSc patients with severe FMD impairment. When we have put these variables in multivariate logistic regression analysis (backward elimination model), we have found an independent association of complement 4 levels (OR: 0.03, [95 % CI: 0.01-0.491], p:0.04) and MRSS values (OR: 0.853, [95 % CI: 0.761-0.955], p:0.006) with significant FMD impairment in patients with SSc. Conclusion Arterial stiffness is significantly increased and endothelial functions, as assessed by FMD is significantly decreased in patients with SSc, when compared to healthy controls. Lower complement 4 levels and lower modified Rodnan skin scores seem to be independently associated with significant severe FMD impairment. Although our study included a remarkable amount of patients with SSc, an infrequent autoimmune disease, number of patients included in our study is not adequate to make more precise comments. Further prospective studies with higher amount of patients are required for certain results.