ASSOCIATION OF ENDOTHELIN-1 WITH PULSE WAVE VELOCITY IN SYSTEMIC SCLEROSIS PATIENTS

Background: Systemic sclerosis (SSc) is a multisystemic disease featured by vascular and immunological disorders along with an excessive accumulation of the components of the connective tissue that cause cutaneous sclerosis and fibrosis of different organs. The occurrence of endothelial dysfunction together with fibrosis indicates that endothelial cell-derived factors, such as endothelin-1 (ET-1), may have an important role in the pathogenesis of SSc. The upregulation of ET-1 activates inflammatory cells and leads to nitric oxide synthase inhibition associated with arterial stiffness. Objectives: The purpose of this study was to evaluate ET-1 serum levels in women with systemic sclerosis (SSc) compared with healthy controls and to examine possible associations between ET-1 and markers of arterial stiffness. Methods: This cross-sectional study was performed in San Cecilio Hospital, Granada (Spain) from November 2017 to May 2019. Sixty-two women with SSc and 62 age and sex matched healthy controls were enrolled in this study. Pulse Wave Velocity (PWV) was measured non-invasively along the carotid–femoral arterial segment. Serum ET-1 was analysed using indirect enzyme-linked immunosorbent assay (ELISA). Results: A total of 62 female patients were included in our study, with a mean (SD) age of 53 ± 10 years. The majority were Caucasian (90.5%). The mean disease duration was 8.8 ± 6.9 years. Forty-four (70.9%) patients had a limited form of the disease and 18 (29.1%) had a diffuse form. There was a significant difference in ET-1 serum levels between SSc female patients and healthy controls (28.4 ± 10.6 vs. 21.1 ± 11.7 pg/ml, p = 0.001). Serum levels of ET-1 were positively associated with PWV (r = 0.26, p < 0.05), within the study group. In addition, in the linear regression model, higher ET-1 concentrations were associated with higher PWV [β = 0.03 95% CI (0.001, 0.060); p < 0.05]. Conclusion: This study shows that ET-1 serum levels are associated with PWV in women with SSc. Therefore, drugs that block ET-1 may be effective in reducing large artery stiffness in women with SSc, and thus cardiovascular risk. REFERENCES: [1]LeRoy EC, Black C, Fleischmajer R, Jablonska S, Krieg T, Medsger TA Jr, et al. Scleroderma (systemic sclerosis): classification, bubsets and pathogenesis. J Rheumatol 1988; 15(2):202-205. [2]Shi-Wen X, Denton CP, Dashwood MR, Holmes AM, Bou-Gharios G, Pearson JD, et al. Fibroblast matrix gene expression and connective tissue remodeling: role of endothelin-1. J Invest Dermatol 2001; 116(3):417–425. [3]Heintz B, Dörr R, Gillessen T, Walkenhorst F, Krebs W, Hanrath P, et al. Do arterial endothelin 1 levels affect local arterial stiffness?. Am Heart J 1993; 126 (4): 987–989. [4]McEniery CM, Qasem A, Schmitt M, Avolio AP, Cockcroft JR, Wilkinson IB. Endothelin-1 regulates arterial pulse wave velocity in vivo. J Am Coll Cardiol 2003; 42 (11): 1975–1981. Disclosure of Interests: None declared Citation: Ann Rheum Dis, volume 80, supplement 1, year 2021, page 1231Session: Scleroderma, myositis and related syndromes (Publication Only)