The goal of this observational study is to characterise the relationships between inflammation, microcalcification and thrombus activity in atherosclerotic plaques in peripheral and systemic vascular territories in patients with symptomatic peripheral arterial disease.

In peripheral arterial disease (PAD), arteries in the lower body can become narrowed and develop blockages due to a process called atherosclerosis, leading to reduced blood flow to the lower limbs. Symptoms can range from mild cramping pain in legs on walking, to loss of parts of the leg. Patients with PAD are also at a high risk of blockages in other arteries in the body that can lead to problems such as heart attacks and strokes. Despite improvements in medical treatments and surgery, the outlook for patients with PAD has not improved.

Further information is required to understand the relationships between the processes that lead to narrowing and blockages (atherosclerosis) of the arteries and if they behave the same in different parts of the body. This can help to identify targeted treatments to reduce the risk of the disease getting worse and avoid heart attacks and strokes.

In this study investigators plan to recruit 100 people with symptomatic PAD to undergo a series of whole body PET-CT and CT angiogram scans using different tracers targeting the processes involved in atherosclerosis. Investigators will aim to co-enrol patients taking part in the LEADER-PAD study (NCT04774159).

Inclusion Criteria:

• Male or female aged > 18 years

• Symptomatic atherosclerotic peripheral artery disease;

  • Intermittent claudication; with ankle/arm blood pressure ratio <0.90 or artery stenosis >50% in addition to at least one of the following;

    • >1 vascular bed affected by atherosclerosis
    • Diabetes
    • Heart failure
    • Chronic kidney disease (eGFR < 60 mL/min/1.73 m2)

  • Rest pain or necrosis of limb or gangrene of limb

  • Revascularization defined as limb bypass surgery or endovascular revascularization procedures (irrespective of the specific device used), including percutaneous transluminal angioplasty/stent of iliac or infra-inguinal arteries or extra-anatomical bypass surgery

  • Leg or foot amputation for arterial vascular indications

• Ability to give written or verbal informed consent

Exclusion Criteria:

• Contraindication to colchicine or iodinated contrast
• Long term requirement for colchicine for another clinical indication
• Active diarrhoea
• Recent lower limb revascularisation for symptomatic disease (<6 weeks)
• Renal failure (glomerular filtration rate <30 mL/min/1.73 m2)
• Cirrhosis or severe chronic liver disease
• Women who are pregnant or breast-feeding
• Women of child-bearing potential not protected by reliable contraception or is planning conception during the study
• Current or planned long term use of cyclosporine, verapamil, HIV protease inhibitors, azole antifungals, or macrolide antibiotics (apart from azithromycin)
• Patients deemed unlikely to return for follow up
• Life expectancy <1 year
• Inability or unwilling to give informed consent

Patients will be prosectively recruited from vascular outpatient clinics and inpatient wards.