Brain Diseases: Peripheral Vascular Disease (PVD, Peripheral Artery Disease, Peripheral Arterial Disease, PAD)

What is peripheral vascular disease?

Peripheral vascular disease (PVD) refers to diseases of the blood vessels (arteries and veins) located outside the heart and brain. While there are many causes of peripheral vascular disease, doctors commonly use the term peripheral vascular disease to refer to peripheral artery disease (peripheral arterial disease, PAD), a condition that develops when the arteries that supply blood to the internal organs, arms, and legs become completely or partially blocked as a result of atherosclerosis.

What is atherosclerosis?

Atherosclerosis is a gradual process whereby hard cholesterol substances (plaques) are deposited in the walls of the arteries. Cholesterol plaques cause hardening of the artery walls and narrowing of the inner channel (lumen) of the artery. The atherosclerosis process begins early in life (as early as teens in some people). When atherosclerosis is mild and the arteries are not substantially narrowed, atherosclerosis causes no symptoms. Therefore many adults typically are unaware that their arteries are gradually accumulating cholesterol plaques. But when atherosclerosis becomes advanced with aging, it can cause critical narrowing of the arteries resulting in tissue ischemia (lack of blood and oxygen).

Arteries that are narrowed by advanced atherosclerosis can cause diseases in different organs. For example, advanced atherosclerosis of the coronary arteries (arteries that supply heart muscles) can lead to angina and heart attacks. Advanced atherosclerosis of the carotid and cerebral arteries (arteries that supply blood to the brain) can lead to strokes and transient ischemic attacks (TIAs). Advanced atherosclerosis in the lower extremities can lead to pain while walking or exercising (claudication), deficient wound healing, and/or leg ulcers.

Picture of Carotid Artery Disease and Plaque Buildup

Picture of Heart Attack (Myocardial Infarction) - Buildup of Cholesterol Plaque and Blood Clot
Atherosclerosis is often generalized, meaning it affects arteries throughout the body. Therefore, patients with heart attacks are also more likely to develop strokes and peripheral vascular disease, and vice versa.

How does atherosclerosis cause disease?

There are two ways atherosclerosis causes disease; 1) atherosclerosis can limit the ability of the narrowed arteries to increase delivery of blood and oxygen to tissues during periods of increased oxygen demand such as during exertion, or 2) complete obstruction of an artery by a thrombus or embolus (thrombus and embolus are forms of blood clots; see below) resulting in tissue necrosis (death of tissue). Exertional angina and intermittent claudication are two examples of insufficient delivery of blood and oxygen to meet tissue demand; whereas strokes and heart attacks are examples of death of tissue caused by complete artery obstruction by blood clots.
There are many similarities between coronary artery diseases (atherosclerosis involving the arteries of the heart) and peripheral artery disease. For example, patients with exertional angina typically have no symptoms at rest. But during exertion the critically narrowed coronary arteries are incapable of increasing blood and oxygen delivery to meet the increased oxygen needs of the heart muscles. Lack of blood and oxygen causes chest pain (exertional angina). Exertional angina typically subsides when the patient rests. In patients with intermittent claudication, the narrowed arteries in the lower extremities (for example, a narrowed artery at the groin) cannot increase blood and oxygen delivery to the calf muscles during walking. These patients experience pain in the calf muscles that will only subside after resting.
Patients with unstable angina have critically narrowed coronary arteries that cannot deliver enough blood and oxygen to the heart muscle even at rest. These patients have chest pain at rest and are at imminent risk of developing heart attacks. Patients with severe artery occlusion in the legs can develop rest pain (usually in the feet). Rest pain represents such severe occlusion that there is insufficient blood supply to the feet even at rest. They are at risk of developing foot ulcers and gangrene.
When the arteries are narrowed as a result of atherosclerosis, blood tends to clot in the narrowed areas, forming a so-called thrombus (plural thrombi). Sometimes pieces of the thrombi break off and travel in the bloodstream until they are trapped in a narrower point in the artery beyond which they cannot pass. A thrombus or piece of thrombus that travels to another point is called an embolus (pleural emboli). Thrombi and emboli can cause sudden and complete artery blockage, leading to tissue necrosis (death of tissue).
For example, complete blockage of a coronary artery by a thrombus causes heart attack, while complete blockage of a carotid or cerebral artery causes ischemic stroke. Emboli originating form atherosclerosis in the aorta (the main artery delivering blood to the body) can obstruct small arteries in the feet, resulting in painful and blue (cyanotic) toes, foot ulcers, and even gangrene.
What are collaterals?
Sometimes, despite the presence of a severe blockage in an artery, the involved area does not become painful or ischemic due to the presence of collateral circulation, meaning that the particular area is supplied by more than one artery to an extent that blockage of a single vessel does not result in a severe degree of ischemia. Collateral circulation can develop over time to help provide oxygenated blood to an area where an artery is narrowed. Doctors believe that regular supervised exercise can stimulate the growth and development of collateral circulation and relieve symptoms of intermittent claudication.

What are complications of peripheral artery disease?

In rare cases, the decreased circulation to the extremities characteristic of peripheral artery disease can lead to open sores that do not heal, ulcers, gangrene, or other injuries to the extremities. These areas that do not receive adequate blood flow are also more prone to develop infections, and in extreme cases, amputation may be necessary.

What are the other causes of peripheral vascular diseases?

A number of conditions such as vasculitis (inflammation of the blood vessels, occurring either as a primary condition or associated with connective tissue diseases such as lupus) may cause damage to blood vessels throughout the body. Injuries to blood vessels (from accidents such as auto accidents or sports injuries), blood-clotting disorders, and damage to blood vessels during surgery can also lead to tissue ischemia.
Tissue ischemia can also occur in the absence of atherosclerosis or other abnormalities of arteries. One example of a condition in which the blood vessels themselves are not damaged is Raynaud's Disease, which is believed to occur due to spasms in blood vessels brought on by stress, tobacco smoking, or a cold environment.
Since atherosclerosis of the peripheral arteries (PAD) is by far the most common cause of peripheral vascular disease, the rest of this article focuses upon peripheral artery disease.

Who is at risk for peripheral artery disease?

Peripheral artery disease (or peripheral arterial disease) is a common condition that affects approximately ten million adults in the U.S. About 5% of people over the age of 50 are believed to suffer from peripheral artery disease. Peripheral artery disease is slightly more common in men than in women and most often occurs in older persons (over the age of 50). The known risk factors for peripheral artery disease are those that predispose to the development of atherosclerosis. Risk factors for peripheral artery disease include:

High blood levels of the bad LDL cholesterol and triglycerides
Low blood levels of the good HDL cholesterol
Cigarette smoking
Diabetes mellitus (both Type I and Type II diabetes)
High blood pressure (hypertension) or a family history of hypertension
A family history of atherosclerotic disease
Chronic renal failure
Overweight or obesity
Physical inactivity

In peripheral artery disease, the risk factors are additive, so that a person with combination of two risk factors- diabetes and smoking for example - have a more likelihood of developing more severe peripheral artery disease than a person with only one risk factor.

What are the symptoms and signs of peripheral artery disease?

Approximately half of people with peripheral artery disease do not experience any symptoms. For patients with symptoms, the most common symptoms are intermittent claudication and rest pain.

Intermittent claudication - Intermittent claudication refers to pain or cramping in the arms or legs that occurs with exercise and subsides with rest. The severity and location of the pain of intermittent claudication vary depending upon the location and extent of blockage of the involved artery. The most common location of intermittent claudication is the calf muscle. The pain in the calf muscle occurs only during exercise such as walking, and the pain steadily increases with continued walking until the patient has to stop due to intolerable pain. Then the pain quickly subsides during rest. Intermittent claudication can affect one or both legs.

Rest pain - Rest pain occurs when the artery occlusion is so critical that there is not enough blood and oxygen supply to the lower extremities even at rest. The pain typically affects the feet, is usually severe, and occurs at night when the patient assumes a supine position (lying down, face up).

Other symptoms and signs of peripheral artery disease include:

Numbness of the extremities
Weakness and atrophy (diminished size and strength) of the calf muscle
A feeling of coldness in the legs or feet
Changes in color of the feet; feet turn pale when they are elevated, and turn dusky red in dependent position
Hair loss over the dorsum of the feet and thickening of the toenails
Painful ulcers and/or gangrene in tissue where there is critical ischemia; typically in the toes.

How is peripheral artery disease diagnosed?

During a physical examination, your doctor may look for signs that are indicative of peripheral artery disease, including weak or absent artery pulses in the extremities, specific sounds (called bruits) that can be heard over the arteries with a stethoscope, changes in blood pressure in the limbs at rest and/or during exercise (treadmill test), and skin color and nail changes due to tissue ischemia.
In addition to the history of symptoms and the physical signs of peripheral artery disease described above, doctors can use imaging tests in the diagnosis of peripheral artery disease. These imaging tests include:

Doppler ultrasound - A form of ultrasound (measurement of high-frequency sound waves that are reflected off of tissues) that can detect and measure blood flow. Doppler ultrasound is used to measure blood pressures behind the knees and at the ankles. In patients with significant peripheral artery disease in the legs, the blood pressures in the ankles will be lower than the blood pressure in the arms (brachial blood pressure). The ankle-brachial index (ABI) is a number derived from dividing the ankle blood pressure by the brachial blood pressure. ABI of .9 to 1.3 is normal, ABI less than 0.9 indicate the presence of peripheral artery disease in the arteries in the legs, and ABI below 0.5 usually indicates severe arterial occlusion in the legs.
Duplex ultrasound - is a color assisted non-invasive technique to study the arteries. Ultrasound probes can be placed on the skin overlying the arteries and can accurately detect the site of artery stenosis as well as measure the degree of obstruction.
Angiography - An angiography is an imaging procedure to study the blood vessels similar to coronary angiogram. It is the most accurate test to detect the location(s) and severity of artery occlusion, as well as collateral circulations. Small hollow plastic tubes (catheters) are advanced from a small skin puncture at the groin (or the arm), under x-ray guidance, to the aorta and the arteries. Iodine contrast "dye," is then injected into the arteries while an x-ray video is recorded. Angiogram gives the doctor a picture of the location and severity of narrowed artery segments. This information is important in helping the doctor select patients for angioplasty or surgical bypass (see below).

Because x-ray angiography is invasive with potential side effects (such as injury to blood vessels and contrast dye reactions), it is not used for initial diagnosis of peripheral artery disease. It is only used when a patient with severe peripheral artery disease symptoms is considered for angioplasty or surgery. A number of different imaging methods have been used in angiography examinations, including x-rays, magnetic resonance imaging (MRI), and computed tomography (CT) scans.

Magnetic resonance imaging (MRI) angiography uses magnetism, radio waves, and a computer to produce images of body structures and has the advantage of avoiding x-ray radiation exposure.

What are the treatments for peripheral artery disease?

Treatment goals for peripheral artery disease include:

Relieve the pain of intermittent claudication.
Improve exercise tolerance by increasing the walking distance before the onset of claudication.
Prevent critical artery occlusion that can lead to foot ulcers, gangrene, and amputation.
Prevent heart attacks and strokes.

Treatments of peripheral artery disease include lifestyle measures, supervised exercises, medications, angioplasty, and surgery.

Lifestyle changes

Smoking cessation eliminates a major risk factor for disease progression and lowers the incidences of rest pain and need for amputations. Smoking cessation is also important for the prevention of heart attacks and strokes.
A healthy diet can help lower blood cholesterol and other lipid levels and may help control blood pressure.
Diabetes control
Blood pressure control
Lipid control

Supervised exercise

Proper exercise can condition the muscles to use oxygen effectively and can speed the development of collateral circulation. Clinical trials have demonstrated that regular supervised exercise can reduce symptoms of intermittent claudication and allow the patients to walk longer before the onset of claudication. Ideally, exercise programs should be prescribed by the doctor. Patients should be enrolled in rehabilitation programs supervised by healthcare professionals such as nurses or physical therapists. For optimal results, patients should exercise at least three times a week, each session lasting longer than 30-45 minutes. Exercise usually involves walking on a monitored treadmill until claudication develops; walking time is then gradually increased with each session. Patients are also monitored for the development of chest pain or heart rhythm irregularities during exercise.

Medications

While lifestyle changes may be enough treatment for some people with peripheral artery disease, others may require medication. Examples of medications used in treating peripheral artery disease include anti-platelet or anti-clotting agents, cholesterol-lowering drugs such as statins, medications that increase blood supply to the extremities such as cilostazol (Petal) and pentoxifylline (Trental), and medications that control high blood pressure.

Antiplatelet medications [such as aspirin and clopidogrel (Plavix)] make the blood platelets less likely to stick to one another to form blood clots. Low dose aspirin (81-325 mg/day) is usually prescribed indefinitely because it is also helpful in preventing strokes and heart attacks in patients with peripheral artery disease. Clopidogrel (Plavix) is an alternative to aspirin for those who are allergic or cannot tolerate aspirin. Anti-platelet medications also help prevent occlusion of blood vessels after angioplasty or bypass surgery.

Anticoagulant medications act to prevent blood clotting. Both heparin and warfarin (Coumadin) are anticoagulant medications. Anticoagulants are sometimes prescribed for people with peripheral artery disease if they are at increased risk for formation of blood clots; these agents are used much less frequently than anti platelet agents in patients with PAD.

Cholesterol-lowering drugs of the statin family have been shown in numerous large clinical trials to help prevent heart attacks and strokes and prolong survival among patients with atherosclerosis. Statins have also been shown to slow the progression of peripheral artery disease, decrease arthrosclerosis in the arteries, and improve claudication symptoms. Current NCEP recommendations for patients with peripheral artery disease are to use diet and medications (such as statins) to lower LDL cholesterol to below 100 mg/dl. Many doctors are now recommending lowering LDL cholesterol even further for patients with peripheral artery disease to below 75-80 mg/dl.

Cilostazol (Pletal) is a mediation that can help increase physical activity (enabling one to walk a greater distance without the pain of claudication). Cilostazol works by causing dilation of the arteries and an increased supply of oxygenated blood to be delivered to the arms and legs. Cilostazol is recommended for some patients with claudication when lifestyle modifications and exercise are ineffective. Cilostazol should be taken on an empty stomach either a half an hour before or two hours after meals. High fat meals, grapefruit juice, and certain medications such as omeprazole (Prilosec) and diltiazem (Cardizem) can increase the absorption and hence the blood levels of Cilostazol. Side effects are generally mild that include headache, diarrhea and dizziness. Cilostazol should not be used in patients with heart failure because of concern over increased mortality in heart failure patients using medications similar to Cilostazol.

Pentoxifylline (Pentoxyl, Trental) was designed and approved to improve blood flow to the extremities by decreasing the viscosity ("stickiness") of blood, enabling more efficient blood flow. Pentoxifylline, in clinical trials, improved walking distance, but its benefits are weaker than those of Cilostazol and have not been conclusively proved by all studies.

Drugs to control hypertension may also be prescribed. There was concern that beta blockers used to treat hypertension can aggravate claudication. But recent studies have not found any adverse effects of beta-blockers on symptoms of patients with peripheral artery disease. Therefore current recommendations are to treat hypertension in patients with peripheral artery disease to prevent strokes and heart attacks.

Angioplasty

Angioplasty is a non-surgical procedure that can widen a narrowed or blocked artery. A thin tube (catheter) is inserted into an artery in the groin or arm, and advanced to the area of narrowing. A tiny balloon on the tip of the catheter is then inflated to enlarge the narrowing in the artery. This procedure is also commonly performed to dilate narrowed areas in the coronary arteries that supply blood to the heart muscle.
Sometimes the catheter technique is used to insert a stent (a cylindrical wire mesh tube) into the affected area of the artery to keep the artery open. In other cases, thrombolytic medications (medications that dissolve blood clots) may be delivered to the blocked area via a catheter.
Angioplasty does not require general anesthesia and may be performed by an interventional radiologist., cardiologist, or vascular surgeon. Usually, a local anesthetic at the area of catheter insertion and a mild sedative are given. Major complications of angioplasty are rare, but can occur. These include damage to the artery or blood clot formation, excessive bleeding from the catheter insertion site, and abrupt vessel closure (blockage of the treated area occurring within 24 hours of the procedure).
Despite these risks, the overall incidence of complications is low and the benefits of angioplasty (no general anesthesia, no surgical incision, and the ability to return to normal activities within a couple of days) outweigh its risks. Usually a one-night hospital stay is required when angioplasty is performed.
Angioplasty is indicated when a patient has claudication that limits his or her activities and does not respond to exercise, medications, and lifestyle measures. Most doctors also recommend angioplasty when disease is very severe and there is a focal, localized narrowing that is accessible via catheter. If a patient is too ill to have surgery and has severe ischemia (decreased oxygen) that threatens loss of a limb, angioplasty may also be attempted.
Some cases of peripheral artery disease may be more difficult to treat by angioplasty. For example, blockages in multiple small arteries of the legs or blockages in extremely small vessels may not be treatable by this method.
Cryoplasty is a newer form of angioplasty in which freezing is used to open a narrowed artery. In this procedure, the balloon on the catheter is filled with liquid nitrous oxide, which freezes and destroys plaques within the artery.

Surgery

Surgical treatment for peripheral artery disease involves either bypass surgery performed by a vascular surgeon or endarterectomy. Indications for surgical treatment of peripheral artery disease include lesions that, for anatomical reasons, may be difficult to treat by angioplasty. Examples include lesions covering long segments of a vessel, vessels with multiple narrowed areas, or long areas of narrowing. Bypass surgery involves using a vein from your body or a portion of synthetic vessel (known as grafts) to create a detour around the blockage. One end of the graft is sewn to the damaged artery above the blockage and the other end is sewn below the blocked area. Blood flow is then able to bypass the area of narrowing or blockage Bypass surgery is a major surgical procedure requiring general anesthesia and a hospital stay.
Endarterectomy is a procedure in which the surgeon cleans out plaque buildup inside the artery of the affected leg or arm.

Peripheral Vascular Disease At A Glance

The term peripheral vascular disease is commonly used to refer to peripheral artery disease (PAD), meaning narrowing or occlusion by atherosclerotic plaques of arteries outside of the heart and brain.
Risk factors for peripheral artery disease include elevated blood cholesterol, diabetes, smoking, hypertension, inactivity, and overweight/obesity.
About 5% of people over the age of 50 are believed to suffer from peripheral artery disease.
The symptoms of peripheral artery disease depend upon the location and extent of the blocked arteries. The most common symptom of peripheral artery disease is intermittent claudication, manifested by pain (usually in the calf) that occurs while walking and dissipates at rest.
Doctors may use radiologic imaging techniques including Doppler ultrasound, and angiography to aid in the diagnosis of peripheral artery disease.
Peripheral artery disease can be treated by lifestyle alterations, medications, angioplasty and related treatments, or surgery.
Complications of peripheral artery disease include sores that do not heal, ulcers, gangrene, or infections in the extremities. In rare cases, amputation may be necessary.
Having peripheral artery disease usually indicates the potential for arterial disease involving the coronary arteries within the brain.

Medical Author:

Melissa Conrad Stöppler, MD

Medical Editor:

Dennis Lee, MD