An in-depth report on the causes, diagnosis, and treatment of peripheral artery disease (PAD).
An in-depth report on the causes, diagnosis, and treatment of peripheral artery disease (PAD).
Peripheral artery disease (PAD) is a type of atherosclerosis, the condition that causes narrowing of the arteries by cholesterol-rich material called plaque. PAD refers to atherosclerosis of arteries in the limbs (most often the legs). Because PAD interferes with circulation, in severe cases procedures may be required to improve blood flow. When PAD is very severe, it can increase the risk for gangrene and can result in a need for amputation. People with PAD are also at increased risk for complications in other arteries, which can lead to heart attacks and stroke.
The main risk factors of PAD include:
Many people with PAD do not have symptoms. When symptoms do occur, leg cramp pain (intermittent claudication) is the main symptom. At first, this symptom occurs with predictable amounts of exercise (walking a certain distance, up a hill or stairs), and disappears when at rest. When PAD becomes more severe, symptoms can include:
Treatment for PAD includes lifestyle measures, medications that help reduce symptoms and prevent disease progression, and surgery. These include:
Peripheral artery disease (PAD) occurs when the arteries in the extremities (usually legs and feet, sometimes arms and hands) become clogged with fat, cells, and other substances, which accumulate and harden into plaque. The build-up of plaque causes the arteries to become narrow and stiff, obstructing blood flow. This hardening and narrowing of the arteries is called atherosclerosis. (Atherosclerosis that affects arteries to the heart and brain is the major process leading to heart disease and stroke.)
PAD most often occurs in the legs. PAD is a type of peripheral vascular disease, which also includes carotid artery disease, renal artery disease, aortic disease, venous problems, and some other conditions, such as vasculitis.
People with PAD may or may not have symptoms. Because symptoms may be mild or even absent, many cases of PAD go undiagnosed.
Claudication comes from the Latin word "to limp." Claudication is leg cramp pain that occurs during exercise, especially walking. The pain is due to insufficient blood flow in the legs (caused by narrowed or completely blocked arteries) to supply oxygen to the working muscles. Intermittent means the pain comes and goes. Intermittent claudication is the most typical symptom of PAD. About one third to one half of people with PAD have this symptom.
Symptoms may be described as pain, ache, cramping, a sense of fatigue, or nonspecific discomfort that occurs with exercise. There is no discomfort while standing. Symptoms go away rapidly with rest. If exercise is restarted, pain will come back after a while and the cycle is repeated, such that the person can predict the distance after which symptoms reoccur. At first, symptoms may only initially develop when walking uphill, walking faster, or walking longer distances.
Intermittent claudication symptoms are most common in the calf muscles. This is because the most frequently affected artery is the popliteal artery, which branches off from the femoral artery (the major artery in the thigh). The popliteal artery continues below the knee where it carries blood to the muscles in the calf and foot. Talk to your doctor about any leg or thigh pain you have.
People may experience muscle pain in one leg or in both legs. People may also have fatigue or pain in the thighs and buttocks.
In advanced cases of PAD, the arteries are so blocked that even rest does not help. Leg pain that continues when lying down is called ischemic rest pain. It is caused by critical limb ischemia, the medical term for insufficient blood flow through arteries of the legs to the muscles and other tissues. Critical limb ischemia is a chronic condition and a very serious form of advanced PAD.
Typical symptoms of critical limb ischemia may include:
People with critical limb ischemia are at risk for developing non-healing skin ulcers and gangrene (tissue death). In severe cases, amputation may be required.
Other signs of advanced PAD can include:
Sometimes, blood clots form in the arteries in the legs, producing abrupt and severe symptoms (acute occlusion).
About 8 million American adults have PAD, and the prevalence of the disease is increasing worldwide. Men and women are equally susceptible although women face a greater risk for limb loss. African Americans have twice the risk for PAD as white people. Between 12% to 20% of people over age 65 suffer from the condition.
The risk factors for PAD are the same as those for heart disease and stroke. Smoking and high cholesterol levels increase the risk for PAD progression in large blood vessels (such as the legs), while diabetes increases the risk for PAD in small blood vessels (such as the feet). Quitting smoking and controlling cholesterol and high blood pressure are the best ways to slow PAD progression.
The most important risk factors for PAD include:
Blood pressure is the force applied against the walls of the arteries as the heart pumps blood through the body. The pressure is determined by the force and amount of blood pumped and the size and flexibility of the arteries.
Peripheral artery disease (PAD) is greatly under-diagnosed. Many people do not report symptoms or may not even have symptoms.
People should be checked for PAD if they have leg pain during walking, or ulcers on their legs. People who may not have symptoms but who should be screened for PAD include those with coronary artery disease, diabetes, chronic kidney disease, or people who have had a previous stroke.
Doctors use the ankle-brachial index (ABI) to screen for PAD. The United States Preventive Services Task Force has determined that the current evidence is insufficient to make a recommendation on ABI screening in asymptomatic patients.
The doctor should check for high blood pressure, heart abnormalities, blockage(s) in the artery in the neck, and abdominal aneurysms. The doctor should also examine the skin of the legs and feet for color changes, ulcers, infection, or injuries, and check the pulse of the arteries in the leg.
Your health care provider may do the following during physical exam:
If someone has a sudden blockage of an artery, the leg or foot may appear chalky white.
The standard diagnostic and screening test for peripheral artery disease is a calculation called the ankle-brachial index. The procedure is done as follows:
The doctor divides the systolic pressure in the ankle by the systolic pressure in the arm. The result is called the ankle-brachial index (ABI), also called ankle-arm pressure index (API).
Who should undergo this test?
What the results mean:
The ABI test is often followed by a treadmill test to find out how exercise affects the blood flow in your extremities. The treadmill test is also useful for determining the severity of the pain while walking and assessing the effectiveness of treatments.
Ultrasound imaging is used to provide an anatomic view of the arteries and report on blood velocity and flow characteristics. A duplex ultrasound combines traditional ultrasound with Doppler ultrasound. These tests can also help identify areas of arterial blockage and help doctors decide which patients may need surgical interventions.
Before considering invasive procedures to treat peripheral artery disease, the surgeon needs a better understanding of which arteries are involved, how severe the blockage is, and the state of the blood vessels surrounding the blockage. In the past, invasive or conventional angiography was typically performed. This type of angiogram uses dye, which is injected through a catheter that is inserted in the groin or arm.
Magnetic resonance angiography (MRA) is a type of magnetic resonance imaging (MRI). It provides a non-invasive alternative to a traditional angiogram. The MRA uses a magnetic field and radiofrequency waves instead of radiation to provide pictures of arteries and blood vessels. People are given gadolinium (a contrast material) through an IV to improve the image quality. In many medical centers, MRA is considered almost or as accurate as invasive angiography and will frequently be the only test required.
Another technology called computed tomography angiography (CTA) uses x-rays to visualize blood flow in arteries throughout the body. This technique is also highly effective in diagnosing PAD.
People with suspected PAD should have an electrocardiogram (ECG) and other tests that can detect heart problems.
The electrocardiogram (ECG) is used extensively in the diagnosis of heart disease, from congenital heart disease in infants to myocardial infarction and myocarditis in adults. There are several different types of electrocardiograms.
A number of other tests may be ordered to rule out disorders with similar symptoms. Such conditions include:
People with peripheral artery disease (PAD) have the same risk of death from heart events or stroke as people already diagnosed with heart disease. The risk increases as PAD gets worse. The worse the leg condition, the poorer is the overall health of the patient.
If people have blood clots and blockages in other arteries (brain, heart) as well as the legs, the risk for any vascular complication involving the heart, the brain, or the leg arteries increases much more.
Severe advanced PAD can cause gangrene (tissue death) that leads to limb amputation. These conditions may result from critical limb ischemia (chronic blockage of arteries in the legs) or acute occlusion (sudden development of blood clot in a major artery of the leg.).
Peripheral artery disease can significantly impair daily physical functioning. Leg pain can limit physical activity, cause unsteadiness, and increase the risk for falling. PAD may also cause erectile dysfunction and it is associated with mental decline.
Symptoms and complications of PAD are likely to progress over time. Overall, more than one fifth of patients who present with symptoms of PAD will progress and experience problems or complications. However, the presence of certain risk factors may predict a more rapid progression. These risk factors include:
There are 2 treatment goals for PAD and claudication.
Lifestyle changes such as smoking cessation and exercise, are critical for every person with PAD. Medication is often required to improve function and protect the heart. In very severe cases, surgery may be needed to improve blood flow.
Treatment for PAD also involves managing the medical conditions (diabetes, high cholesterol, and high blood pressure) that often accompany it.
People with diabetes (type 1 or type 2) need to strictly control their blood sugar (glucose) levels. Poor glycemic control is associated with vascular and circulation complications such as PAD. People should aim for an A1c level around 7%. The A1c test measures a person's average blood sugar over the past 2 to 3 months. People with diabetes need to follow certain dietary restrictions. Many different types of medications are used to control blood sugar levels.
It is very important for people with PAD to keep their LDL (bad cholesterol) levels controlled. The latest guidelines recommend high-potency statin therapy to control cholesterol in people with PAD. Unhealthy cholesterol levels are major contributors to atherosclerosis, the common factor in PAD and heart disease.
People should follow lifestyle principles to reduce unhealthy cholesterol levels including consuming a heart-healthy diet, engaging in regular physical activity (the AHA recommends 150 minutes of moderate activity or 75 minutes of vigorous activity per week), and maintaining a healthy body weight.
Most people with PAD should aim for blood pressure less than 130/80 mm Hg. But people with diabetes may need to have a lower systolic (top number) or diastolic (bottom number) goal. Ask your doctor what your target blood pressure goal should be.
People should be sure to follow dietary measures to reduce sodium (salt) and increase potassium intake. The DASH diet is a good example of a diet plan based on these principles.
Various medications are used to control high blood pressure (hypertension). There is some evidence that the best drugs for people with high blood pressure and PAD may be angiotensin-converting-enzyme (ACE) inhibitors.
People who smoke should quit, and everyone should avoid second-hand smoke. Smoking is one of the primary risk factors for PAD and a major cause of complications. Quitting smoking may not make leg pain go away, at least not in the short term, but it certainly may keep blockages from getting worse. Continued smoking is a major reason why people progress from milder forms of PAD to critical limb ischemia involving severe pain, skin ulcers, and possible amputation. Smoking cessation also reduces the risk to the heart and brain.
Exercise is second only to avoiding tobacco as the most important lifestyle measure for treating, and preventing, PAD.
Exercise to Help the Heart
The benefits of regular moderate exercise for the heart are undisputed. People who maintain an active lifestyle have a much lower risk of developing heart disease than do sedentary people. According to the American Heart Association, patients with PAD who are physically active have death rates that are a third of those who are less physically active.
Exercise Training to Improve Blood Flow in the Legs
Exercise training improves blood flow in the legs and, in some cases, can work as well as medications and surgical procedures in increasing pain-free walking distance. To maintain benefits, exercise must be regular and consistent. A regular walking program, either outside or on a treadmill, is the best type of exercise for people with PAD and can significantly slow the rate of functional decline.
For people with intermittent claudication who find that their leg cramps make it difficult to walk or participate in lower-extremity exercise, upper-body aerobic exercise can still provide benefits.
The goals of a heart-healthy diet are to:
Any diet should also help keep blood pressure and weight under control. General guidelines for a heart-healthy diet include:
While vitamin deficiencies may be associated with PAD and heart disease, vitamin supplements have not been proven to reduce the risk for heart-related conditions. Low levels of vitamin D are linked to an increased risk of PAD, and many older Americans are deficient in this vitamin. More research is needed to determine if vitamin D supplements protect against PAD.
Deficiencies in the B vitamins folate and B12 are associated with elevated levels of homocysteine, an amino acid that may be a marker for increased risk for heart disease and PAD. However, while vitamin supplementation lowers homocysteine levels, it has no effect on heart disease outcomes. Similarly, vitamin E and other multivitamin supplements do not help PAD symptoms.
Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Always check with your health care provider before using any herbal remedies or dietary supplements.
Ginkgo biloba is an herbal remedy reported to have blood-thinning properties. However, studies have shown it does not provide any benefit for people with PAD or intermittent claudication. Although the risks for ginkgo appear to be low, there is an increased risk for bleeding at high doses and harmful interaction with high doses of anti-clotting medications. This is particularly important because people with PAD often use these types of medications. Commercial ginkgo preparations have also been reported to contain colchicine, a chemical that can be harmful in pregnant women and people with kidney or liver problems.
Medications for PAD help prevent blood clots and reduce the risk for heart attack and stroke.
Antiplatelet drugs such as aspirin prevent blood clots. Most people with peripheral artery disease receive antiplatelet medication. For the most part, this recommendation is made to prevent future death from heart attack or stroke. Antiplatelet drugs may or may not provide benefit for PAD symptoms and progression.
Aspirin (75 to 100 mg per day) is usually the recommended first-line choice to prevent heart attack or stroke in people with PAD. It is also recommended to be started before any surgical procedure and continued afterwards without stopping or bypasses on arteries below the inguinal area. However, recent studies have indicated that aspirin may not have much benefit in preventing heart attack or stroke in people who have PAD without also having heart disease.
Clopidogrel (Plavix, generic) (75 mg per day) is another antiplatelet drug that is sometimes used as an alternative to aspirin. Clopidogrel plus aspirin is recommended for people after bypass graft surgery that uses a man-made or prosthetic graft performed on arteries below the knee.
Vorapaxar (Zontivity) is a new type of antiplatelet drug approved to lower risk of heart attack, stroke, or heart disease death for people who have peripheral artery disease or those who have had a heart attack. It is the first in a new class of drugs called protease-activated receptor-1 (PAR-1) antagonists. People who have had a stroke should not use this drug because the risk of bleeding is too great.
Research indicates that adding an anticoagulant drug, such as warfarin (Coumadin, generic), to antiplatelet therapy does not help prevent heart complications of PAD, and can increase the risks for life-threatening bleeding. Coumadin may be used in some people after bypass surgery that utilizes a venous graft, if concern for clotting is high.
All antiplatelet drugs can increase the risks for bleeding.
Statins are the most common type of medication used to help lower LDL cholesterol and improve lipid profiles. Cholesterol management is a very important part of PAD treatment. Current guidelines recommend statin therapy for all people with PAD.
Statin drugs include:
ACE inhibitors are a type of drug used to treat high blood pressure. These drugs block the effects of the angiotensin-renin-aldosterone system, which is associated with many harmful effects on the heart and blood vessels. They are important drugs for patients with PAD and diabetes who also have high blood pressure.
In addition to heart protection, ACE inhibitors may help reduce pain that patients experience when walking. The ACE inhibitor ramipril (Altace, generic) is often specifically recommended for people with symptomatic peripheral artery disease. Studies indicate that in addition to reducing the risk of cardiovascular events, ramipril may help improve walking ability and quality of life in people with intermittent claudication.
ACE inhibitors include:
Phosphodiesterase inhibitors are drugs that help improve blood flow. They may be prescribed to treat intermittent claudication.
Cilostazol (Pletal, generic) is used to treat disabling intermittent claudication. A number of studies have reported that the drug helps improve walking distance and quality of life. It also helps improve HDL and triglyceride levels. Cilostazol works better than pentoxifylline, the first drug approved for claudication. However, it is expensive, and currently recommended only for people with moderate-to-severe intermittent claudication who do not respond to aspirin or less costly treatments.
Common side effects include headache, swelling in the limbs, and stomach problems such as diarrhea and flatulence (gas). It does not appear to have bad effects on the liver or kidney. Similar drugs can have serious side effects in patients with heart failure, so patients with heart failure should avoid cilostazol.
Pentoxifylline (Trental, generic) reduces the sticky properties of blood cells, improving blood flow. It is approved in the United States for managing claudication, although doctors do not recommend its routine use. Studies regarding the drug's effectiveness have been mixed. Some studies have reported a small effect on walking ability; another found the drug significantly improved walking distance. Other research has found that the drug does not work any better than a dummy pill (placebo). The most common side effects include headache, nausea, heartburn, flatulence (gas), dizziness, blurred vision, and flushing.
In severe cases of PAD, surgery may be needed to open blocked blood vessels. Many different types of surgical procedures can be performed. They include open bypass procedures, which connect an artery before the location of the obstruction to an artery below the obstruction, or minimally invasive endovascular techniques such as angioplasty and stenting. The location of the lesions and how many other risk factors and illnesses patients have often determine which procedure is chosen.
Surgery is generally performed for claudication that has become disabling despite full medical and exercise therapy. Surgery may also be necessary for patients with rest pain, and to save a limb when a person develops critical limb ischemia and is in danger of amputation.
A grading system helps classify peripheral artery disease in patients in a manner that suggests who will do better with any type of surgery, as well as whether bypass surgery or percutaneous angioplasty and stent is a better choice. The system takes into consideration which arteries are involved, as well as how many arteries and how many parts of an individual artery are narrowed. The age of the patient and how disabled they are by other medical problems must also be considered. Before any procedures, all patients must be evaluated further risk of having heart complications or a stroke during any surgical procedure.
For many years, leg bypass surgery was the main type of surgery used for extensive PAD. This procedure involves the creation of a tube (graft) that acts as a new blood vessel. Grafts can be made from synthetic material (artificial vein) or from a vein taken from a different location in the person's leg (natural vein). The graft reroutes blood flow in the leg, around the blocked artery. Possible bypass connections between arteries include aorta to iliac arteries, aorta to femoral arteries, and bypass between the femoral artery and popliteal, tibial, and peroneal arteries.
Artificial veins tend to pose a much higher risk for blood clots, and the consequences of re-blockage are must more severe than when the natural vein recloses. To keep the artificial vein open, oral anti-clotting drugs such as aspirin or warfarin may be used. (Such drugs do not work with natural vein bypass.)
In general, less invasive procedures, such as balloon angioplasty and stenting, are now more frequently performed.
Percutaneous transluminal angioplasty (PTA) is an approach that has several variations. The object of the procedure is to open the blocked blood vessels that are causing intermittent claudication. Angioplasty is being increasingly used in place of leg bypass surgery, especially in patients who have other medical conditions.
Although not exclusively, percutaneous treatment is more likely to be recommended for those with focal narrowing of the aorta or iliac arteries, such as the common and external iliac arteries.
The PTA procedure requires only a local anesthetic. People can return to normal activity in 24 to 48 hours. Complication rates are low. The effects are not permanent, but the procedure can be repeated with minimal risk.
Anticoagulants (such as warfarin or heparin) and antiplatelets (such as aspirin) may be used to prevent blood clots occurring during surgery. All of these drugs increase the risk for bleeding.
Thrombolytic drugs such as alteplase (Activase) and reteplase (Retavase) may be used intravenously before, during, or after angioplasty if a blood clot is present. Such drugs are commonly called "clot-busters." They break up existing clots, and may be used in cases of acute vascular occlusion (the sudden development of a blood clot).
The standard procedure is balloon angioplasty. A thin tube is inserted through an artery in the groin and passed through the blocked artery. A wire is threaded through the tube. A deflated balloon is passed over the wire to the blockage. When inflated, it opens the artery.
Because balloon angioplasty poses a risk for reclosure of the artery, various other procedures are used or are being investigated.
Re-blockage of the blood vessels from blood clotting, even long after surgery, is a major complication. To help prevent this complication, and repeat surgery, a tiny expandable metal mesh tube (stent) is often used along with angioplasty. However, even with stents, some people experience new blockages within a year of surgery. Some angioplasties are performed with a drug-eluting stent, which is coated with the drug paclitaxel to help prevent blockages from occurring in the stents.
Drug-eluting stents may not be recommended for people who had recent heart surgery, or women who are nursing or pregnant. People who receive a drug-eluting stent may need to take blood thinning drugs for at least several months.
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Reviewed By: Deepak Sudheendra, MD, RPVI, FSIR, Director of DVT & Complex Venous Disease Program, Assistant Professor of Interventional Radiology & Surgery at the University of Pennsylvania Perelman School of Medicine, with an expertise in Vascular Interventional Radiology & Surgical Critical Care, Philadelphia, PA. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Medical Director, Brenda Conaway, Editorial Director, and the A.D.A.M. Editorial team.
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