Peripheral artery disease: detection and treatment

Understanding the disease

Peripheral arterial disease (PAD) is a common condition that occurs when arteries become blocked or narrowed, reducing the flow of blood to the limbs. In the U.S., PAD currently affects more than 8.5 million adults over the age of 40, and it is estimated that more than 19 million Americans will have the disease by 2050.¹ Worldwide, the incidence of PAD increased by 23.5% between 2000 and 2010² and that growth is expected to continue.

Peripheral artery disease is most common in the lower limbs; this form occurs in 12% to 20% of Americans.² The primary cause of PAD is atherosclerosis — the buildup or hardening of plaque within the arteries.

This buildup can lead to a variety of symptoms and signs in patients including:

• Painful cramping in hips, thighs or calf muscles after certain activities, such as walking or climbing stairs
• Leg numbness or weakness
• Coldness in lower leg or foot, especially when compared with the other side
• Sores on toes, feet or legs that won't heal
• Change in the color of legs
• Hair loss or slowed hair growth on feet and legs
• Slowed growth of toenails
• Shiny skin on legs
• Weak or no pulse in legs or feet
• Erectile dysfunction in men
• Pain or cramping when using arms

If detected early, PAD can be managed with lifestyle changes and medication; however, if left untreated, PAD can lead to worsening health conditions — including limb amputation, heart attack, stroke and death. In 2018, PAD was the underlying cause of more than 12,500 deaths.³

Risk factors and detection

Peripheral arterial disease affects both men and women; however, it is slightly more prevalent in men. The disease is also more common in Black Americans.⁴ Age is a risk factor, with prevalence increasing to 50% in Americans 85 years and older. A history of smoking is also a significant risk factor; one study found that more than 80% of patients diagnosed with PAD were current or former smokers.²

Other risk factors include:

• High blood pressure
• Diabetes mellitus
• High cholesterol
• Chronic kidney disease

Early detection of PAD is vital to the treatment and management of the disease, but detection can be challenging. One significant challenge is low awareness of the disease among both patients and nonvascular physicians and clinicians. In a survey conducted by the American Heart Association in 2018, only 26% of adults 50 years or older were familiar with PAD. In comparison, 56% of adults in that age group were aware of coronary artery disease.¹ As a result, patients suffering from PAD often mistake their symptoms for other conditions.

There are various methods of diagnosing the condition, including ankle-brachial index (ABI) test, ultrasound, computed tomographic angiography, and duplex ultrasonography.³ The primary method for diagnosing the disease is the noninvasive ABI test, which compares systolic blood pressure in the upper and lower limbs. The measurement in the lower limb is divided by the measurement in the upper; a ratio < 1 indicates PAD. The inflatable cuff used for the ABI test can be used at various points in the lower extremities, including the toes, thigh, calf and foot.⁵

Current treatment options

Treatment for PAD has two major goals⁶: To stop the progression of atherosclerosis throughout the patient’s body, thereby reducing risk of heart attack or stroke, and to manage symptoms or pain to enable the patient to resume physical activity.

Selecting the best treatment pathway can be a complex decision based on the overall health of the patient, history of vascular problem(s) and the location and severity of the arterial blockage.⁷ In mild cases, patients may be able to manage or possibly stop the progression of the disease by making lifestyle changes, especially if the disease is detected early.

Lifestyle changes that can help mitigate PAD include⁸:

• Quitting smoking
• Eating a balanced diet
• Exercising
• Managing other health conditions
• Practicing good foot and skin care

In some cases, medication may be necessary to modify risk factors, reduce limb-related morbidity,⁹ or manage symptoms.

Treatment for severe cases

In more severe cases of PAD, minimally invasive treatment or surgery may be recommended. Angioplasty and atherectomy are two common minimally invasive procedures. Angioplasty involves inflating a balloon within the blocked portion of the artery or blood vessel and then placing a stent to maintain blood flow. Atherectomy involves navigating a specialized catheter into the blocked artery or vessel to remove plaque.

Peripheral bypass surgery is another treatment, and offers an option for patients who:

• Are not candidates for angioplasty or atherectomy
• Previously underwent angioplasty without success
• Possess a narrowed or blocked portion of the artery that is elongated

Peripheral bypass surgery entails attaching a graft above & below the blocked portion of an artery or vessel to reroute blood flow through an unobstructed conduit. Two primary factors — the material used for bypass grafts and the condition of the arteries to which the grafts are attached — determine the short- and long-term success of the procedure.⁷

Types of vascular grafts

Autologous grafts taken from the patient, such as sections of the saphenous vein or internal mammary artery,¹⁰ are most commonly used in peripheral vascular bypass graft procedures for two reasons. First, due to their higher patency rates and also because they allow for a normal physiologic response from the vascular wall to control thrombosis and clotting. In cases where an autologous graft is not an option, alternatives include allografts and synthetic grafts.

A cryopreserved allograft — a biologic graft sourced from a human cadaver — closely resembles native tissue and provides a similar vascular wall response as an autologous graft.¹¹ However, allografts have disadvantages — in particular, they have a poor primary patency rate at one year. Higher secondary patency and limb salvage rates, however, continue to support the use of cryopreserved allografts.¹²

Synthetic vascular grafts are another alternative to autologous veins. Synthetic grafts are made of nondegradable polymers that allow flexibility, length and ability to tailor the viscoelasticity and tensile strength. Materials currently in use for synthetic grafts include expanded polytetrafluorethylene (ePTFE), polyethylene terephthalate (Dacron), and polyurethane.

Exploring modified synthetic grafts to increase patency

Studies of the potential use of synthetic polymers as bypass grafts, do not demonstrate patency rates and thromboresistance equivalent to an autologous graft.¹⁰ Therefore, suppliers are exploring coatings, chemical modifications and endothelial cell seeding to the surface of synthetic materials to improve patency rates and thromboresistance. Such modified synthetic grafts have the potential to reduce the need for later revisions, increase amputation-free survival and decrease the total cost of care.¹³

One is bonding the anticoagulant heparin onto nondegradable polymers. Gore Propaten Vascular Grafts (Gore Medical), which has shown success, are ePTFE grafts that use end-point covalent technology to bond heparin to the graft surface while maintaining its bioactivity to help prevent clotting (Figure 2). The heparin-coated graft has been shown to reduce acute graft thrombosis after implantation, compared with a standard ePTFE graft.¹³

Figure 2: Gore Medical Propaten heparin-coated synthetic graft

© 2022 Gore Medical. All rights reserved. Used with the permission of Gore Medical.

The Gore Propaten graft has demonstrated an average primary patency rate of 46% at year 4 in below-knee bypasses (Figure 3), an increase of nearly 60% compared with standard uncoated grafts.¹³ This, as well as increased secondary patency, led to a 36% decrease in revision procedures, a 28% increase in amputation-free survival and an overall 38% decrease in average cost after year three of implantation, compared with standard ePTFE grafts.¹⁴

Figure 3: Average primary patency rates for heparin-coated synthetic graft at years 1-5

© 2022 Gore Medical. All rights reserved. Used with the permission of Gore Medical.

Daenens et al noted that, “Overall, our results...provide solid additional evidence that heparin-bonded ePTFE grafts represent an important new option in the treatment of peripheral arterial disease.”¹³