PAD means the arteries are narrowed or blocked—the vessels that carry oxygen-rich blood as it moves from the heart to other parts of the body.

Peripheral veinous disease, on the other hand, refers to problems with veins—the vessels that bring the blood back to the heart.

[3] Complications may include an infection or tissue death, which may require amputation; coronary artery disease; or stroke.

[7][19] PAD is primarily caused by the buildup of fatty plaque in the arteries, which is called atherosclerosis, especially in individuals over 40 years old.

[19] The most common presenting symptom is intermittent claudication (IC), which typically refers to lower extremity skeletal muscle pain that occurs during exercise.

Other complications of severe PAD include lower limb tissue loss (amputation), arterial insufficiency ulcers, erectile dysfunction, and gangrene.

[37] The factors with the greatest risk associations are hyperlipidemia, hypertension, diabetes mellitus, chronic kidney disease, and smoking.

[52] In the early stages of PAD, the arteries compensate for plaque buildup by dilating to preserve flow through the vessel.

From the pathophysiologic point of view, a restriction of blood supply (ischemia) to the lower limbs can be classified as either functional or critical.

Functional ischemia occurs when the blood flow is normal at rest but insufficient during exercise, presenting clinically as intermittent claudication.

In this situation, precise diagnosis is fundamental, as there is a clear risk of limb loss if adequate blood flow is not re-established, either by surgery or endovascular therapy.

[54] Diagnosing or identifying peripheral artery disease requires a history of symptoms and a physical exam, followed by confirmatory testing.

[31] A physician will examine an individual for specific exam findings if symptoms are consistent with peripheral artery disease.

If an ABI >1.40 is calculated, this could indicate vessel wall stiffness caused by calcification, which can occur in people with uncontrolled diabetes.

Abnormally high ABIs (>1.40) are usually considered false negatives, and thus, such results merit further investigation and higher-level studies.

[42][50] If ABIs are abnormal, the next step is generally a lower limb Doppler ultrasound to look at the site of obstruction and the extent of atherosclerosis.

Any blood flow-limiting blockage found in the X-ray can be identified and treated by procedures including atherectomy, angioplasty, or stenting.

[citation needed] Modern computerized tomography (CT) scanners provide direct imaging of the arterial system.

An important distinction between the two is that, unlike invasive angiography, assessment of the arterial system with CT does not allow for vascular intervention.

The advantages of MRA include its safety and ability to provide high-resolution, three-dimensional imaging of the entire abdomen, pelvis, and lower extremities in one sitting.

[65] Recently, the Society for Vascular Surgery came out with a classification system based on "wound, ischemia and foot infection" (WIfI).

[66] This classification system, published in 2013, was created to account for the demographic changes that have occurred over the past forty years, including the increased incidence of high blood sugar and evolving techniques and abilities for revascularization.

This system was created on the basis that ischemia and angiographic disease patterns are not the sole determinants of amputation risk.

This is because resting perfusion and metabolic activity are extremely low and differences between non-patients and PAD patients are barely measurable.

[71] Pulse oximeters can be inconvenient to wear during exercise and only give oxygen values at discrete time points, nor is there sufficient evidence to support any use in identifying PAD.

Some publications and studies therefore discuss the use of wearable sensors measuring oxygen levels continuously in PAD patients, such as through transcutaneous means.

[42] For chronic limb-threatening ischemia, the ACCF/AHA guidelines recommend balloon angioplasty only for people with a life expectancy of 2 years or less or those who do not have an autogenous vein available.

[83] Individuals with PAD have an "exceptionally elevated risk for cardiovascular events and the majority will eventually die of a cardiac or cerebrovascular etiology".

[90] In those who have developed critically poor blood flow to the legs, the benefit of autotransplantation of autologous mononuclear cells is unclear.

[94][95] In 2011, pCMV-vegf165 was registered in Russia as the first-in-class gene therapy drug for the treatment of PAD, including the advanced stage of critical limb ischemia.