Peripheral Arterial Disease

Peripheral arterial disease affects approximately 6% of adults globally^[1] and is characterized by atherosclerosis (a build-up of fatty plaques in arteries) causing a narrowing or blockage of arteries supplying blood to the limbs, usually the lower limbs.^[2][3] Peripheral arterial disease lowers a person’s quality of life (due to pain and poor mobility), increases their risk of requiring a lower limb amputation, and raises their risk of dying from coronary heart disease.^[2][3]

The main symptom of peripheral arterial disease is lower-leg pain, aching, or cramping that develops during physical activity (e.g., walking) and subsides after stopping. This symptom is called intermittent claudication. One other symptom which suggests more severe disease is lower leg and foot pain when lying down, which improves when the leg hangs down. This symptom is called rest pain. People with peripheral arterial disease may also have cold or numb toes and notice persistent sores or ulcers on their legs.^[2][3]

The signs of peripheral arterial disease include clinical tests showing a weak or absent pulse in the feet, muscle atrophy and weakness in the lower leg, poor muscle oxygenation during exercise, and leg pain during a treadmill walking test.^[2][3]

To make a diagnosis, people with signs and symptoms of peripheral arterial disease undergo a resting ankle-brachial index (ABI) test. This test uses Doppler ultrasound to compare blood pressure in the ankles with blood pressure in the arms, at rest. In some people, a resting ABI test is followed up with an exercise ABI test during treadmill walking. A person with an abnormal ankle-to-arm blood pressure ratio (e.g., ABI ≤ 0.90) is typically followed up with ultrasound imaging, magnetic resonance angiography, or computed tomographic angiography. These imaging tests visualize the affected arteries to identify the location of narrowing (stenosis) or blockage (occlusion) and to measure the extent to which the narrowing/blockage has progressed. These tests help inform the subsequent therapeutic approach.^[2]

Treatment of peripheral arterial disease focuses on the “modifiable” risk factors: smoking, physical inactivity, high blood glucose, high blood lipids, and high blood pressure.^[2][3][4]

• Stopping smoking reduces the risk of amputation and heart attack, and prolongs survival.^[5]
• Regular exercise relieves intermittent claudication (calf pain during walking) and improves exercise capacity and quality of life.^[6][7]
• Lipid-lowering drugs lessen the risk of coronary events.^[8][9] If the patient has diabetes or hypertension, glucose-lowering and blood pressure-lowering therapies are also recommended.^[2][10]

Other drugs are also used to lessen symptoms of intermittent claudication and improve walking distance (e.g., cilostazol^[11]) and to help prevent major cardiovascular events (e.g., clopidogrel^[12][13]).

Several supplements have been studied in people with peripheral arterial disease. These include alpha-lipoic acid, arginine, carnitine, creatine, fish oil (which contains omega-3 fatty acids), flaxseed, ginkgo biloba, nitrate, resveratrol, etc. For many of these supplements, including creatine, omega-3 fatty acids, and ginkgo biloba, there is no clear benefit.^{[14][15][16][17][18][19]} However, carnitine supplementation lowers intermittent claudication (calf pain during exercise) and increases walking distance in people with peripheral arterial disease.^[20] Furthermore, emerging data show that nitrate supplementation can improve limb blood flow, vascular function, and exercise capacity in people with peripheral arterial disease.^{[21][22][23][24]}

In some studies, a higher saturated fat intake is associated with a greater risk of peripheral arterial disease.^[25] Furthermore, one intervention study found that people randomized to a Mediterranean diet had a lower risk of developing peripheral arterial disease compared to people receiving a control diet.^[26][27] But, due to a lack of high-quality randomized controlled trials, the direct effects of specific diets (e.g., a Mediterranean diet) or specific nutrients (e.g., saturated fat) on peripheral arterial disease are unclear and require further investigation.^[28] In general, these dietary patterns can also modify the risk of other vascular diseases (e.g., coronary artery disease) that share the same underlying mechanism of disease: atherosclerosis, the narrowing or blockage of arteries due to fatty plaques.^[29][30][31]

When the main treatments are insufficient to treat the symptoms of peripheral arterial disease, revascularization is also used to restore blood flow to lower limbs.^[2][3][4] This typically involves a procedure called balloon angioplasty, which widens blocked or narrowed arteries, consequently relieving intermittent claudication (calf pain during exercise) and improving exercise capacity and quality of life.^[32][33]

Emerging treatment options include nitrate drugs (e.g., nitroglycerin), to improve blood flow; autologous stem cell therapy, to increase vascularization; and lower extremity electrical stimulation, to improve functional capacity.^[4][34] But these options require further investigation before firm conclusions about their safety and efficacy are possible.

The narrowing or blockage of arteries in peripheral arterial disease is caused by a progressive build-up of fatty plaques in the lining of the affected artery.^[4] This complex process is called atherosclerosis, and it is influenced by genetics and promoted by lifestyle factors such as smoking, diet, physical inactivity, and excessive weight gain.^[4]