Abstract
Keywords
What is peripheral artery disease (PAD)?
Peripheral artery disease (PAD) is a condition in which cholesterol-rich plaques, also known as atherosclerosis, deposit in the walls of the leg arteries, those blood vessels that take oxygenated blood from the heart to the organs and tissues. When atherosclerotic plaques develop, they may not cause any symptoms at first, but as they grow and the artery becomes narrowed, PAD may cause the symptoms described below due to difficulty getting enough blood past the blockages.
In 2024, a new guideline regarding the management of PAD was published. 1 This updated Patient Information Page reflects the best practices for care of patients with PAD as outlined in the 2024 guidelines.
Who is at risk for PAD?
PAD is common, affecting more than 10 million people in the United States. 1 Smoking and diabetes are the two most important factors that lead to PAD. The risk of developing PAD increases with age; adults 65 years and older are at higher risk for PAD than younger people. Traditional risk factors for coronary artery disease (CAD, or the atherosclerotic blockages that can lead to heart attack) also increase the risk for PAD. These risk factors include high blood pressure (hypertension), high cholesterol, family history of cardiovascular disease (CVD), and chronic kidney disease. People with known CAD and atherosclerosis in other areas of the body are at risk for PAD. Black people are at increased risk for developing PAD. Unfortunately, they are also more likely to have their PAD undertreated due to inequalities in health care. 2
What are the symptoms of PAD?
Some patients with PAD may have no symptoms if the plaque buildup does not significantly block blood flow. The most well-known symptom of PAD is muscular leg pain with walking, known as claudication. With claudication, blockages are not severe enough to cause pain at rest, when muscles require less oxygen and blood flow. When a person with blockage walks and the exercising muscle needs more oxygen, the lack of sufficient blood to that part of the leg causes pain. Patients may feel a cramp, ache, burning sensation, or muscle fatigue or weakness with walking, especially when walking uphill or climbing stairs. These symptoms go away with rest.
Nearly all people with PAD have functional impairment, which is reduced ability to walk. Either they may be limited by their claudication, or they may subconsciously decrease their walking because of leg discomfort. PAD may also lead to a decreased sense of physical and mental well-being, which can be measured on questionnaires about quality of life.
Severe PAD may cause pain at rest, which is often in the foot and worse when the leg is elevated. In this case, the pain may be worse at night when in bed. The pain may be improved by dangling the leg out of the bed, as gravity helps blood flow all the way to the foot. People with severe PAD may develop nonhealing sores on the toes or heels owing to pressure from a poorly fitting shoe, for example, or injury. This advanced form of PAD is known as chronic limb-threatening ischemia (CLTI).
In the most dramatic form of PAD, a piece of plaque may break off and travel to a smaller part of the artery lower in the leg or a clot can form on top of a plaque, where it completely blocks blood flow. This is known as acute limb ischemia (ALI), and the blood- and oxygen-starved leg may be pale and cool to the touch and may lose sensation or movement. ALI is a medical emergency that must be treated immediately with a procedure to open up the artery.
How is PAD diagnosed?
PAD may be suspected on physical examination, when pulses in the legs and feet are decreased compared with normal. Patients who are at risk for PAD should remove their shoes and socks and ask to have their feet and pulses inspected at each office visit.
The best initial test for diagnosing PAD is the ankle–brachial index (ABI). 3 The ABI is a simple, widely available, noninvasive test that uses blood pressure differences between the arms and legs, measured by a handheld Doppler ultrasound device, to detect PAD. In people with normal leg arteries, the blood pressure obtained at the ankle is higher than the arm (Figure 1). The ABI is calculated as shown in Figure 1. A normal ABI is between 1.0 and 1.4.
How to calculate an ankle–brachial index (ABI). Image created in BioRender: https://BioRender.com/e15t416.
The ABI may be falsely elevated in patients with diabetes or chronic kidney disease, which can cause the arteries to be stiff and poorly compressed by the blood pressure cuffs. In that case, supplemental information may be needed to make the diagnosis. Additional testing may be performed if the diagnosis is not clear after calculating the ABI, or if a patient is planning to undergo a procedure for PAD. Other imaging options include duplex ultrasound, computed tomographic angiography (CTA), or magnetic resonance angiography (MRA), as shown in Figure 2.
(A) Ultrasound of the right superficial femoral artery near the groin. The lack of color at the white arrow shows a complete blockage of the artery. (B) Computed tomographic angiography (CTA) of the abdomen and pelvis. The white arrow shows calcium-rich plaque in the aorta and common iliac arteries, which provide blood flow to the legs. (C) Angiogram of the right leg. The arrow points to multiple stents placed in the artery to prop it open.
CTA and MRA require contrast dye, which is injected through an IV and causes the arteries to be better visible in the images. In traditional contrast angiography, dye is injected through a catheter, a small tube placed directly into an artery, to create a real-time picture of the arteries on a type of X-ray called fluoroscopy. Although angiography is an invasive procedure performed under sterile conditions in an angiography suite (also known as a catheterization laboratory or ‘cath lab’), one of its advantages is that a procedure to open blocked arteries can be performed at the same time imaging is obtained.
What are the risks of having PAD?
People with PAD are at risk for decreased physical functioning and impaired physical and psychological quality of life. PAD is considered a high-risk atherosclerotic disease, and PAD increases the risk of atherosclerosis in other parts of the body, including the arteries of the heart, the neck and brain, and the kidneys. As a result, people with PAD are at high risk for heart attack and stroke.
Perhaps the most feared complication of PAD is leg amputation. People who have severe PAD are at increased risk for amputation, as are people with PAD and diabetes and people who continue to smoke cigarettes after PAD diagnosis. Black people are at higher risk for amputation, which may be the first treatment offered for PAD because they are often diagnosed with PAD late in the course of the disease due to unequal access to medical care and other geographical and environmental factors. 2 Many patients who undergo a major limb amputation—that is, an amputation of the leg below or above the knee—are at increased risk of dying within the next year.
How is PAD treated?
Treatment of PAD is focused on three major areas: preventing CVD-related illness and death; improving physical functioning and walking ability; and preventing amputation (Table 1).
Summary of treatment goals for peripheral artery disease.
ACE, angiotensin-converting enzyme; ALI, acute limb ischemia; ARB, angiotensin receptor blocker; CLTI, chronic limb-threatening ischemia; CVD, cardiovascular disease; GLP-1, glucagon-like peptide-1; PAD, peripheral artery disease; PCSK9, proprotein convertase subtilisin/kexin type 9; SGLT2, sodium-glucose cotransporter-2.
Preventing CVD/PAD-related illness and death
To prevent heart attack, stroke, and CVD-related death, all patients with PAD with symptoms should be on low-dose (‘baby’) aspirin or an alternative antiplatelet medication such as clopidogrel. Certain patients with PAD should also be on a low-dose anticoagulant (blood thinner) medication called rivaroxaban, taken twice a day. In large studies, aspirin and rivaroxaban together have been shown to reduce the risk of CVD-related illness and death.
Patients with PAD should be on a high-intensity statin medication such as atorvastatin (40–80 mg) or rosuvastatin (20–40 mg) to lower cholesterol, even if their baseline cholesterol level is normal. The goal low-density lipoprotein (LDL) cholesterol, or ‘bad’ cholesterol, is less than 70 mg/dL; an LDL less than 55 mg/dL is preferred in very high-risk patients. Ezetimibe and/or newer cholesterol-lowering medications called PCSK9 inhibitors may be added if the cholesterol remains above the goal, or in patients who are not able to tolerate statin medications.
Controlling hypertension is important to reduce CVD risk. Patients with PAD should be started on a blood pressure-lowering medication called an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). Additional medications may also be needed to maintain blood pressure less than 130/80 mmHg.
It is essential that patients who smoke quit smoking immediately to reduce the risk of heart attack, stroke, and amputation. Quitting smoking is best accomplished through either varenicline or combination nicotine replacement therapy with patches plus nicotine gum or lozenges. 4
Patients with type 2 diabetes and PAD are candidates for medications called glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT2) inhibitors to control blood sugar and reduce the risk of CVD-related illness and death.
Improving physical functioning and walking ability
The first-line treatment for claudication is walking exercise, either through a supervised exercise therapy program at a health facility or home-based structured exercise. 5 Patients are asked to walk until they have moderate pain, at which point they rest until the pain or discomfort eases. Once the pain has eased, the patient starts walking again. Over time, structured walking exercise can increase the pain-free walking distance by up to double, but the key to improving is walking until it hurts. Patients who undertake a walking exercise program should ensure that their shoes fit properly and do not rub, which could lead to skin breakdown.
Patients with claudication may also be prescribed a medication called cilostazol, which has been shown to increase the pain-free walking distance by about half. However, some patients do not tolerate cilostazol because of gastrointestinal side effects or palpitations; it may also cause a headache initially.
Patients who are still limited by their symptoms after an exercise program should be offered a revascularization procedure to open up the affected artery and improve or restore blood flow. Revascularization procedures include angioplasty, in which a balloon inserted into the artery during angiography is inflated to compress the plaque against the wall, often followed by placement of a stent – a small metal scaffold that props the artery open. Some patients are not candidates for angioplasty with a stent and may undergo open surgical procedures to restore blood flow. For patients with ALI or CLTI, revascularization procedures are an important part of patient care.
Preventing amputation
Low-dose rivaroxaban has been shown to reduce the risk of amputation in patients with PAD. Patients who are candidates for this medication should be started on rivaroxaban in addition to low-dose aspirin. Patients who are on anticoagulant therapy for other reasons (e.g., atrial fibrillation, prior blood clots) and those who take medications like clopidogrel and ticagrelor in addition to aspirin (e.g., patients who have had recent coronary artery stents) are not candidates for low-dose rivaroxaban.
Patients with diabetes should control their blood sugar and have regular foot care with a podiatrist (foot doctor). Uncontrolled diabetes increases the risk of amputation due to nonhealing foot ulcers that may progress to require amputation.
All patients with PAD (with or without diabetes) should look at their feet, including the soles, every day; a mirror can be helpful. Because of poor blood flow to the feet, people who get sores or wounds on their feet are at risk for nonhealing wounds that may eventually require amputation. Daily foot inspection can identify minor injuries that may worsen without attention. Patients who have leg or foot pain with rest or nonhealing ulcers on their feet should have urgent revascularization to prevent progression to amputation.
What is recommended for long-term follow-up of PAD?
Patients with PAD should be seen in the clinic regularly for assessment of leg symptoms, walking ability, and CVD risk factors. At each visit, pulses and feet should be checked and medications should be reviewed. Multispecialty care is recommended, which may include a cardiovascular or vascular medicine specialist, a diabetes specialist, a podiatrist, and other specialists.
How can PAD be prevented?
The best prevention for PAD is to avoid smoking and avoid the development of diabetes. Regular medical care to identify and treat high blood pressure and high cholesterol may reduce the risk of PAD. Maintaining a healthy body weight and exercising daily may also be helpful. A diet high in vegetables, fruits, legumes, nuts, and whole grains may be helpful in decreasing the risk of PAD. People should be aware of the symptoms of PAD and ask their doctor to check the pulses in their feet.
Summary
PAD is common and causes leg discomfort with walking and reductions in physical functioning. It also increases the risk of heart attack and stroke. PAD is most commonly diagnosed using a simple, noninvasive test called the ABI. Patients with PAD should take medications to reduce the risk of CVD-related illness and death and amputation. Those with decreased walking ability should participate in walking exercise programs, but some people may need to undergo procedures to open up blocked blood vessels. All patients with PAD must check their feet frequently.
Footnotes
Acknowledgements
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
Dr Elizabeth Ratchford’s work was supported in part by the generosity of David Kotick (1926–2021).
