Evaluation of sex-based differences in below-the-knee plaque histology in patients who underwent amputation for chronic limb-threatening ischemia

Objective: With the growing incidence of peripheral arterial disease (PAD) and the historic under-representation of female patients in cardiovascular trials, a comprehensive evaluation of sex-based variances in PAD presentation and treatment outcomes is needed. This study aims to evaluate sex-based differences in the vessel wall characteristics of patients who underwent amputation owing to critical limb-threatening ischemia to optimize personalized treatment planning and aid in the selection of endovascular devices for PAD patients. Methods: A total of 35 lower limbs were collected from 34 patients with end-stage PAD undergoing major amputation. We selected, harvested, and cross-sectioned at 3- to 4-mm intervals 163 diseased below-the-knee arterial segments resulting in 1260 arterial rings. Histological analyses were conducted on each individual ring and later summarized by arterial segment. Results: Male and female patients were remarkably similar across multiple plaque characteristics, including degree of stenosis, calcification severity and localization, and atherosclerotic patterns. A significant sex-based difference was noted in the presence of luminal thrombus, which was more prevalent in females (38.7% vs 25.0%; P =.016). Histopathological differences were noted between popliteal and tibial lesions, with popliteal segments demonstrating increased chronic total occlusion presence and atherosclerosis, whereas severe calcification occurred more often in tibial segments. A sex-based evaluation of the popliteal segments showed increased calcification (60.71% vs 28.0%; P =.003) and atherosclerosis (96.4% vs 73.0%; P =.028) in males compared with females. Conclusions: Differences in the degree of calcification, incidence of atherosclerosis, and presence of luminal thrombus may pose important clinical implications for antiplatelet and anticoagulation regimen choice and guide treatment options. Further studies are warranted to evaluate the impact of these differences on outcomes of endovascular procedures.