Abstract
OBJECTIVE: To evaluate the impairment of nitric oxide (NO)-mediated vascular function in patients with systemic sclerosis (SSc) compared with healthy controls through passive leg movement (PLM), which is a noninvasive technique largely dependent on NO bioavailability. METHODS: Twenty-one patients with SSc and 21 age- and sex-matched healthy controls were recruited. PLM was performed in a sitting position, and blood flow was assessed at the level of the right common femoral artery, distal to the inguinal ligament, and approximately 2 cm from the femoral artery bifurcation, by measuring flow velocity and vessel diameter. Resting blood flow, peak flow during PLM, and the area under the blood flow versus time curve (AUC) were calculated. Patients with SSc were stratified by disease phenotype and treatment regimens. RESULTS: Patients with SSc showed significantly reduced PLM responses compared with controls (peak flow: 467.7 ± 97.8 vs 552.5 ± 151.9, P = 0.038; ΔPeak:153.3 ± 59.8 vs 220.2 ± 82.7, P = 0.005; AUC: 57.1 ± 38.9 vs 89.3 ± 38.1, P = 0.01), indicating impaired NO-mediated vasodilation. No significant differences in PLM results were found across SSc phenotypes. An inverse correlation was observed between modified Rodnan Skin Score and femoral artery diameter (P = 0.001), suggesting vascular remodeling. Pharmacologic treatments, including vasoactive and immunosuppressive agents, did not significantly impact PLM parameters. Statin use was associated with lower baseline blood flow (P = 0.031). CONCLUSION: PLM responses are significantly reduced in patients with SSc, confirming the role of NO-mediated endothelial dysfunction in SSc, independent of disease subtype or treatment status. PLM may serve as a noninvasive biomarker for microvascular health in SSc and underscore the need for therapies that directly target the endothelium. Larger, longitudinal studies are warranted to confirm these results and explore PLM's prognostic utility.