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OP0240 ASSESSMENT OF PULSE WAVE VELOCITY IN SYSTEMIC SCLEROSIS: POTENTIAL BENEFICIAL EFFECTS OF BOSENTAN ON FOREARM ARTERIAL STIFFNESS? AN EXPLORATORY STUDY

Background Systemic sclerosis (SSc)-related vasculopathy is generally thought to occur on a microvascular level. However, some observations also suggest involvement of arterial vessels. Macrovascular involvement (e.g., aorta or upper extremity) can be non-invasively assessed by measuring pulse wave velocity (PWV). Although, several studies have assessed aortic and upper extremity PWV in SSc, studies have not reached a consensus regarding this matter. Furthermore, we hypothesized that the endothelin antagonist bosentan may improve arterial stiffness by its direct endothelial and potential anti-fibrotic effects. Objectives The aim of this exploratory study was two-fold. First, we aimed to compare arterial stiffness in patients with SSc and age and sex-matched healthy controls (HC). Secondly, we will investigate the effect of bosentan on both short-term (three month) and long-term (one year) PWV. Methods Baseline differences between HC and SSc patients were studied in a case-control design. The follow-up of SSc patients was a randomized, prospective, 2-arm parallel group, open-label, (usual care with bosentan versus usual care only), blinded endpoint, intervention study. PWV (Sphygmocor) in meters/second, was measured to assess arterial stiffness in the aorta (carotid-femoral PWV), upper arm (carotid-brachial PWV), and forearm (brachial-radial PWV), adjusted for mean arterial pressure. Results Baseline characteristics are shown in table 1. No significant differences were observed in PWV (at all sites) between HC and SSc patients. No effect of bosentan on aortic, and upper arm PWV was found. The change in forearm PWV was different between the groups, with a decrease (e.g. lowering arterial stiffness) in the bosentan group (figure 1).Table 1 Baseline characteristics Healthy controls (n=19) Systemic sclerosis patients (n=19) Bosentan group (n=9) Usual care group (n=7) Female, n (%) 13 (69) 13 (69) 5 (56) 6 (86) Age in years, median (IQR) 53 (47–63) 50 (44–54) 52 (49–66) 44 (43–54) Pack years, median (IQR) 0 (0–7.5)* 2.5 (0–30.6)* 17.3 (0.7–34.1) 0.8 (0–2.75) Body mass index in kg/m², median (IQR) 25 (23–27) 25 (21–29) 25 (22–27) 26 (20–37) Systolic blood pressure in mm Hg, median (IQR) 130 (121–137) 127 (123–134) 126 (117–142) 127 (123–132) Diastolic blood pressure in mm Hg, median (IQR) 81 (72–88) 85 (79–89) 84 (76–87) 83 (79–85) Raynaud’s phenomenon duration in years, median (IQR) N/A 8.0 (4.0-13.0) 1.0 (1.0–7.0) 13.0 (6.0–16.0) Systemic sclerosis disease duration since first non-Raynaud symptom in years, median (IQR) N/A 2.0 (1.0–7.0) 1.0 (1.0–7.5) 5.0 (2.0–14.0) *difference between groups with a p<0.05Figure 1 The median (IQR) of the brachial-radial pulse wave velocity over time of the bosentan and usual care group Conclusion This small study shows that aortic, upper arm, and forearm arterial stiffness does not appear to be increased in patients with SSc, as compared to age- and sex-matched healthy controls. To the best of our knowledge, this is the first study to investigate the concept of potential effects of an endothelin receptor antagonist on macrovascular involvement in SSc. Although the results demonstrate no effects on aorta and upper arm arterial stiffness, they may indicate a beneficial effect on the stiffness of the smaller arteries of the forearm. Future studies are needed to further investigate the potential effect of bosentan on these smaller arteries. Acknowledgement Actelion for co-funding the study Disclosure of Interests Anniek van Roon: None declared, Amaal Eman Abdulle : None declared, Saskia van de Zande: None declared, Arie Van Roon: None declared, Dan Zhang: None declared, Reinhard Bos Grant/research support from: SUN Pharma, Hendrika Bootsma Grant/research support from: Unrestricted grants from Bristol-Myers Squibb and Roche, Consultant for: Roche, Bristol-Myers Squibb, Novartis, Medimmune, Union Chimique Belge, Speakers bureau: Bristol-Myers Squibb, Novartis, Andries Smit Shareholder of: Has been co-founder, and is still shareholder of Diagnoptics Technologies, the company which developed the AGE reader., Douwe J Mulder Grant/research support from: My University has received research grants for my research from: Boehringer Ingelheim and Actelion, Speakers bureau: My University has received speakers fee from: Sanofi