Early Perioperative Changes in Circulating Hypoxia-Inducible Factor-1 Alpha (HIF-1A) and Vascular Endothelial Growth...

Background: Peripheral arterial disease (PAD) is characterised by chronic limb ischaemia and frequently coexists with metabolic comorbidities like diabetes mellitus. Surgical revascularisation performed to relieve symptoms of ischaemia induces an abrupt transformation from hypoxia toward normoxia. However, the early systemic behaviour of hypoxia-responsive angiogenic pathways during this period remains incompletely characterised. Methods: In this prospective, single-centre observational study, 26 patients undergoing elective above-knee femoropopliteal bypass for PAD were enrolled. Venous samples were collected preoperatively (T0), immediately postoperatively (T1), and 24 h after surgery (T2). Circulating hypoxia-inducible factor-1 alpha (HIF-1A) and vascular endothelial growth factor (VEGF) were quantified, and their temporal changes were analysed. Exploratory subgroup analyses were also performed according to diabetes status. Results: Both circulating HIF-1A and VEGF declined significantly following revascularisation, with reductions detectable immediately postoperatively and persisting at 24 h. Baseline HIF-1A and VEGF concentrations were strongly correlated. While baseline biomarker levels did not differ by diabetes status, patients with diabetes exhibited an attenuated postoperative decline in circulating HIF-1A at 24 h, with a similar but non-significant trend observed for VEGF. Conclusions: Lower limb revascularisation for PAD is associated with a rapid and sustained decline in circulating hypoxia-responsive angiogenic markers, consistent with early resolution of hypoxia-driven signalling. Diabetes status was associated with altered postoperative biomarker trajectories, supporting further investigation of early perioperative angiogenic dynamics in PAD.