Histological concordance of medial arterial calcification between tibial and peroneal arteries in advanced peripheral arterial disease.

Background: Medial arterial calcification (MAC) is prevalent in peripheral artery disease (PAD), yet its distribution and clinical significance in infrapopliteal arteries remain poorly defined. Prior histopathological studies of distal tibial segments have not evaluated MAC as a vessel-level lesion. Peroneal arteries (PAs) are frequently regarded as relatively spared revascularization targets based on angiographic assessment alone, despite limited histological validation and emerging evidence that arterial medial remodeling contributes independently to limb ischemia. Accordingly, it remains unclear whether MAC in PAD reflects a diffuse distal arterial phenotype shared across tibial and peroneal segments or a segment-specific process. Methods: This single-center prospective pilot study included 14 patients and 14 limbs (13 patients with PAD and 1 control without PAD) undergoing below-knee amputation. Paired anterior tibial arteries (ATAs) and PAs were harvested, formalin fixed, and paraffin embedded. Hematoxylin and eosin staining was used to assess arterial architecture, intimal plaque, and medial remodeling. MAC was graded 0 to 4 using Alizarin Red staining according to circumferential extent and thickness. Clinical variables included age, sex, ethnicity, diabetes mellitus (DM), hemoglobin A1c, end-stage renal disease stage, smoking status, glucagon-like peptide-1 receptor agonist use, Rutherford category, and limb outcomes. Results: The cohort included 92.3% males with an average age of 69.0 ± 10 years and a high prevalence of DM, consistent with larger PAD series. Moderate to severe (grades 3-4) MAC was common in limbs with PAD. Within-patient concordance of MAC grades between paired ATA and PA was high, with most pairs differing by ≤1 grade, supporting a diffuse rather than a segment-specific distal arterial phenotype. A greater MAC burden was observed in patients with DM, advanced end-stage renal disease, and higher Rutherford categories, but these exploratory associations were not statistically significant. Directional trends were observed between histological MAC burden and adverse limb outcomes, consistent with prior radiographic studies. Conclusions: In this pilot human tissue study, MAC appears to represent a shared distal arterial phenotype across ATAs and PAs in PAD rather than a segment-specific lesion. Histology-confirmed MAC burden provides biologic validation of distal calcification patterning and may help to refine our understanding of infrapopliteal disease in advanced PAD. Larger, multicenter studies are warranted to define the prognostic utility of MAC-based indices and to determine how tissue-level calcification patterns relate to clinical imaging and revascularization strategies. Clinical relevance: In advanced peripheral artery disease, medial arterial calcification (MAC) appears to be a shared distal arterial phenotype rather than a lesion confined to a single infrapopliteal vessel. The high concordance between paired anterior tibial artery and peroneal artery specimens suggests that the histological assessment of one distal artery may reflect limb-wide MAC burden, which could help to refine the risk stratification and interpretation of infrapopliteal disease. These findings also support the concept that the peroneal artery is not histologically spared in severe peripheral artery disease, despite its frequent consideration as a revascularization target. Larger studies integrating tissue histology, imaging, and clinical outcomes are needed to determine whether MAC burden can improve prediction of limb loss and guide procedural planning.