Sortilin is a 95-kDa protein related to circulating cholesterol. It is found inside different cell types and circulating in blood and it has been associated with the risk of atherosclerosis development and cardiovascular diseases.

The goal of this observational study is to evaluate the potential use of circulating sortilin as a biomarker of vascular adverse outcomes in patients with peripheral artery disease (PAD) and chronic limb-threatening ischemia (CLTI) requiring a procedure of endovascular revascularization.

The main questions it aims to answer are:

• association between sortilin serum levels and risk of restenosis after lower extremity revascularization.
• association between sortilin serum levels and acute limb ischemia, major vascular amputations, and limb-threatening ischemia needing for urgent revascularization after lower extremity revascularization.

Patients with PAD and CLTI requiring lower extremity endovascular revascularization will undergo blood sampling for the dosage of circulating sortilin before the endovascular procedure.

Incidence of restenosis and acute limb ischemia, major vascular amputations, and limb-threatening ischemia needing for urgent revascularization will be collected in a 12-months follow-up and will be associated with sortilin serum levels at baseline.

Inclusion Criteria:

• type 2 diabetes mellitus diagnosis;
• Ankle/Brachial Index (ABI) of less than 80;
• at least one lower limb stenosis greater than 50% documented by Ultrasound Color Doppler (US);
• stage 4 or 5 PAD diagnosis according to the Rutherford classification;
• presence of chronic limb threatening ischemia;
• indication for LER of the target arterial stenosis.

Exclusion Criteria:

• statin therapy within the previous 3 months;
• revascularization of the lower limb in the previous 3 months;
• diabetic foot ulcers with signs of active infection or osteomyelitis;
• diabetic peripheral neuropathy;
• homozygous familial hypercholesterolemia;
• absolute contraindication to antiplatelet therapy;
• thrombophilia;
• active cancer;
• active autoimmune disease;
• liver disease at functional status B or C according to Child-Pugh.

We will enroll consecutive statin-naïve subjects with type 2 diabetes mellitus with PAD requiring for endovascular revascularization and admitted to Internal Medicine Cardiovascular Unit of the Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma.