Peripheral artery disease (PAD), also known as peripheral arterial disease, is a condition in which the arteries that supply blood to the legs or, less frequently, the arms become narrowed or blocked, resulting in reduced blood flow. It’s most commonly caused by atherosclerosis, a disease in which plaque builds up on the inner walls of arteries, causing them to narrow and harden, thereby reducing blood flow through them.

While many people with PAD don’t have any symptoms, the condition can cause pain or discomfort in the affected limb during exercise, but the pain will resolve at rest. For instance, people with PAD may have leg pain while walking or climbing stairs but experience pain relief after resting. This type of presentation is called “claudication” and can impact an individual’s quality of life.

In more advanced stages of the disease, the pain may become constant (called “rest pain”). The affected limb, or part of it, may feel numb or weak, and ulcers can develop on it. In severe cases, the reduction in blood flow can cause gangrene (tissue death). In medical terms, this stage is referred to as “chronic limb-threatening ischemia,” or CLTI. As the name implies, there is a threat to the limb, and some patients may have to undergo a major amputation of their foot if blood flow is not restored.

According to the National Institutes of Health (NIH), around 10 million Americans ages 40 and over have PAD. The condition can affect both men and women, though it is more common in men. While people of any age can develop PAD, the risk for the condition increases as people age, and in the U.S., it most frequently occurs in people ages 65 or older.

While there is no cure for PAD, effective treatments can reduce symptoms and slow the progression of the disease.

Arteries are blood vessels that transport oxygen- and nutrient-rich blood from the heart to organs and tissues throughout the body, allowing them to work properly and stay healthy. The arteries that deliver blood to the arms, hands, legs, and feet are called peripheral arteries.

In an individual with PAD, one or more of the peripheral arteries have become narrowed or blocked, reducing blood flow. As a result, less blood than normal reaches the legs, feet, arms, and/or hands, which can lead to a number of symptoms and complications.

PAD most commonly occurs in leg arteries (known as lower extremity PAD), causing symptoms in the leg, foot, and/or toes. Less commonly, it can also affect the arms (called upper extremity PAD), leading to symptoms in the arm, hand, and/or fingers.

PAD can occur in one leg or both legs at the same time, depending on which arteries are affected. People may also have upper and lower extremity PAD simultaneously.

PAD is most commonly caused by atherosclerosis, a disease in which plaque builds up in the arteries, causing them to narrow and stiffen, thereby reducing the amount of blood that flows through them. Because atherosclerosis can affect arteries throughout the body, people with PAD often have other cardiovascular conditions, such as coronary artery disease, that are also caused by plaque buildup in the arteries.

Less commonly, other conditions, such as physical trauma, blood clots, blood vessel inflammation, and/or radiation exposure, can cause similar symptoms. Some disorders that affect the walls of blood vessels, such as certain types of vasculitis and fibromuscular dysplasia, can also compromise blood flow to the extremities and are important to recognize.

Risk factors for PAD include:

• Cigarette smoking, including exposure to secondhand smoke
• A diet high in saturated fat, cholesterol, and/or processed meat
• A sedentary lifestyle
• High blood pressure
• High cholesterol
• Type 1 diabetes and type 2 diabetes
• Chronic kidney disease
• Obesity
• Increasing age, especially among those ages 65 years or older
• Having atherosclerosis in other arteries
• Family history of PAD, heart disease, atherosclerosis, and/or stroke
• Hyperhomocysteinemia (in which there are elevated levels of homocysteine, an amino acid, in the blood)

Many people with PAD don’t have any symptoms. When symptoms are present, however, they may include the following:

Lower extremity PAD:

• Leg claudication that usually occurs in the calves but can also affect the thighs and buttocks
• Pain, typically in the foot, at rest that could get worse during sleep as the person is lying flat
• Prickling, burning, numbness, or weakness in the affected leg or foot
• Cold foot and/or toes
• Leg, foot, and/or toes that appear pale or bluish
• Hair thinning or loss on the affected limb
• Dry, shiny skin
• Brittle, ridged, thick, and/or slow-growing toenails
• Weakness and possibly paralysis of the affected limb
• Ulcers on the leg, foot, and/or toes
• Wounds and ulcers that fail to heal
• Gangrene (that typically affects the toes or foot)
• Erectile dysfunction

Upper extremity PAD:

• Arm claudication
• Hand or finger pain while at rest
• Hands and fingers that appear pale or bluish
• Coldness in hands and fingers
• Paleness in hand and fingers
• Prickling, burning, numbness, or tingling sensation in the arm, hand, or fingers
• Ulcers on the fingers
• Gangrene

A diagnosis of PAD typically involves a review of your medical history, a physical exam, and one or more diagnostic tests.

Your doctor will ask you about your symptoms and whether you have any known risk factors for PAD, such as a history of smoking, high blood pressure, diabetes, and cardiovascular disease, among others.

During a physical exam, your doctor will examine your skin for signs of PAD, check for weak pulses in your arms and legs, and inspect your feet for ulcers or wounds.

To diagnose PAD, your doctor may also perform or order other tests, including:

• Ankle-brachial index (ABI). ABI is used to diagnose PAD in the lower extremities. In this noninvasive test, you lie flat on your back with your arms and legs at the same level as your heart. Then, the blood pressure in both arms and ankles is measured using a Doppler ultrasound probe to listen to the pulse in the artery. The ABI for the right and left sides of the body is based on the arterial pressure ratio in the ankle compared to that of the arm or brachial artery. An ABI between 0.9 and 1.4 is considered normal; lower extremity PAD is diagnosed when the ABI is lower than 0.9.
• Segmental Doppler pressure testing. In this test, which is typically done with an ABI, you lie flat on an exam table for 15 minutes to stabilize your blood pressure. Three to four blood pressure cuffs are then wrapped around your arm or leg at different points. Using Doppler ultrasound, the doctor measures the blood pressure of each cuff. If a difference in the blood pressure at different levels of the arm or leg is large enough, it can help your doctor locate where the artery is narrowed or blocked.
• Exercise ABI. Your doctor may perform this test if you have claudication, but your resting ABI is normal. For this test, you will undergo an ABI test after walking on a treadmill. It is used to diagnose lower extremity PAD.
• Arterial duplex. This test uses an ultrasound probe to measure the velocity of the flow inside the arteries and can localize the areas that are severely narrowed. It can also visualize the plaque and the calcium in the walls of the vessel. It is not invasive and is typically performed in the office.
• Additional imaging tests, including a computed tomography (CT) scan or magnetic resonance imaging (MRI), typically with intravenous injection of contrast material to better visualize the arteries. These tests provide accurate details about the complete anatomy of the arteries, including the location of disease areas. They are typically reserved for planning interventions or surgical operations or in selected cases where additional anatomical information is needed that cannot be provided by an ultrasound.

Treatment for peripheral artery disease depends on the patient’s symptoms. However, regardless of symptoms, a diagnosis of PAD carries a significant risk of death and illness. As a result, each patient with PAD should immediately be put on the best medical therapy for them.

In general, the goals of treatment are to reduce symptoms, improve quality of life, reduce the risk of losing a limb due to PAD, and reduce the risk of other cardiovascular events, such as heart attack or stroke.

Treatments for PAD include:

• Lifestyle changes, which can help relieve symptoms and prevent the development of cardiovascular disease. These changes may include:
  • Quitting smoking
  • Getting regular physical exercise (supervised walking is the recommended first-line therapy for patients with claudication)
  • Eating a heart-healthy diet
  • Keeping blood sugar levels under control (especially for those with diabetes)
  • Taking care of your feet to prevent ulcers and infection
  • Maintaining a healthy weight
• Medications, which can help reduce symptoms and prevent complications. Medications may include:
  • Antiplatelet drugs, to reduce the risk of blood clots, thereby lowering the risk of heart attack and stroke. These medications—such as aspirin or clopidogrel—may reduce PAD symptoms and increase the distance that people with lower extremity PAD can walk.
  • Statins, to reduce cholesterol levels, slow the progression of atherosclerosis, reduce the risk of complications from PAD, and help lower the risk of cardiovascular disease. Statins are recommended in patients with PAD regardless of their cholesterol level.
  • Cilostazol, a vasodilator that can reduce pain from claudication and increase the distance people with lower extremity PAD can walk.
• Endovascular interventions, which are minimally invasive procedures typically performed through a puncture in the groin. Under X-ray guidance and advanced imaging, wires, catheters, and dedicated devices can be introduced to the area of narrowing and used to open the blockage, thereby improving blood flow to the limb.
  
  Endovascular techniques for the treatment of PAD include:
  • Angioplasty, a procedure in which a health care provider directs a catheter equipped with a balloon at its tip to the narrowed or blocked portion of the artery, then inflates the balloon, causing the artery to open, restoring blood flow. Sometimes, the balloon is coated with a drug that helps prevent re-narrowing of the blood vessel. At the end of the procedure, the balloon and catheter are removed.
  • Stenting. In some cases, the provider may insert a stent—a tube made of mesh wire—into the narrowed part of the artery to assist in keeping the area open after balloon angioplasty. Stents may be used when there are heavy blockages that can recoil or narrow back rapidly after balloon angioplasty. The stent may also be coated with a medication to prevent the blood vessel from narrowing again.
  • Atherectomy, a minimally invasive procedure for removing plaque buildup in an artery. In atherectomy, a health care provider inserts a catheter equipped with a rotating blade, a burr, or a laser into the affected artery, then uses the instrument to remove or evaporate the plaque, effectively widening the artery to improve blood flow.
• Surgical procedures for treating PAD, which include:
  
  
  • Arterial bypass graft, a procedure in which the blood flow through an artery is rerouted to go around a narrowed or blocked section of the artery rather than through it. In this procedure, a surgeon attaches a graft—a blood vessel (typically a vein) taken from elsewhere in the body or a tube composed of manmade materials—above and below the narrowed or blocked section of the affected artery. Blood then flows through the graft and, thus, bypasses the narrowed or blocked portion of the artery.
  • Endarterectomy, a procedure in which a surgeon makes an incision in the skin above the affected artery, cuts open the affected artery, surgically removes plaque from it, and then uses bioprosthetic material when closing the artery to make it wider and less likely to narrow again.

In some cases, both endovascular and surgical procedures are used in combination to treat PAD. This is known as a hybrid approach.

The decision to perform surgery to improve the blood flow depends on the individual’s symptoms and treatment goals. In general, the approach is the following:

• Patients without symptoms typically do not need endovascular intervention or surgical procedures.
• Patients with claudication should be treated medically first. If their symptoms significantly interfere with their lifestyle despite medical therapy, intervention or surgery to improve blood flow or revascularization may be recommended.
• Patients with CLTI, rest pain in their feet (typically), or wounds that do not heal within a month should undergo revascularization as they are at risk for a major amputation.

People with PAD may be at an increased risk for the following complications:

• Inadequate blood supply to the affected limb, leading to gangrene, which may need to be treated with amputation
• Heart attack
• Stroke
• Transient ischemic attack (TIA), also known as a “mini-stroke”
• Erectile dysfunction
• Infection

The outlook for people with PAD varies depending on their underlying risk factors, the severity of the condition, and the location of the narrowed or blocked artery, among other factors.

While PAD cannot be cured, lifestyle changes, medications, and other treatments can reduce symptoms and help slow or prevent the progression of the disease. Many people with PAD, however, also have coronary artery disease or narrowing or blockages in other arteries due to atherosclerosis, which increases their risk for heart attack or stroke.

“At Yale, patients with PAD get complete and comprehensive care for their disease, including medical, endovascular, and surgical therapies in addition to programs to help with lifestyle changes, such as smoking cessation and supervised walking, among others,” says Cassius Iyad Ochoa Chaar, MD, MPH, MS, a Yale Medicine vascular surgeon with extensive expertise in the management and research of PAD. “Also, Yale offers cutting-edge technology with clinical trials for patients with challenging anatomy and with no traditional options for revascularization.”

Yale is involved in several clinical trials related to PAD. Notably, two trials bring unique treatment options for patients with PAD. One is called “Double blind randomized autologous stem cell trial treatment for peripheral arterial disease (PAD) with critical limb threatening ischemia.” The other is “Percutaneous Deep Vein Arterialization for the Treatment of Late-Stage Chronic Limb-Threatening Ischemia: The PROMISE III Trial.”