Peripheral ischaemia – Diagnostics – Overview of Information and Clinical Research

Peripheral ischaemia, also known as peripheral artery disease or PAD, affects millions of people worldwide and occurs when narrowed arteries reduce blood flow to the limbs, usually the legs. Many people with this condition don’t realize they have it because symptoms can be mild or absent altogether, yet early diagnosis is crucial for preventing serious complications and improving quality of life.

Introduction: Who Should Undergo Diagnostics and When

If you experience leg pain when walking that goes away with rest, it’s time to see your doctor. This symptom, though often dismissed as a normal part of aging, may signal peripheral ischaemia and should never be ignored. Many people mistakenly think recurring leg pain during exercise is just something they have to live with, but this isn’t true for an otherwise healthy person^[1].

Diagnostics for peripheral ischaemia are particularly important for people over 60 years old, as the condition affects 12% to 20% of Americans in this age group, with prevalence increasing to nearly 50% in those 85 years and older^[2]. However, you should seek testing earlier if you have certain risk factors. These include smoking or tobacco use, diabetes, high blood pressure, high cholesterol, or a family history of heart disease or stroke^[3].

Black individuals should be especially aware of their risk, as they face higher chances of developing peripheral ischaemia compared to non-Hispanic white people, particularly after age 50 for men and age 60 for women^[4]. The presence of three or more risk factors can increase your odds of having the disease by ten times^[5].

You should also consider testing if you notice other warning signs beyond leg pain. These include coldness in your lower leg or foot, hair loss or slowed hair growth on your legs, shiny or smooth skin on your legs or feet, color changes in your legs or feet (turning pale, blue, or purple), numbness or weakness in your legs, brittle or slow-growing toenails, or open sores on your feet and legs that won’t heal^[6]. Men may also experience erectile dysfunction, which is the inability to achieve or maintain an erection, as this can be related to blockages in the arteries that supply the pelvic area^[7].

⚠️ Important

If your symptoms develop quickly or suddenly get much worse, this could be a sign of a serious problem requiring immediate treatment. Seek medical care right away if you suddenly lose feeling in your foot and cannot move it, or if it becomes blue, very pale, or colder than the other foot. These are signs of a medical emergency that needs urgent attention^[8].

More than 20% of patients with peripheral ischaemia have no symptoms at all, and nearly the same percentage experience atypical symptoms that don’t fit the classic pattern^[9]. This means you could have the condition without knowing it. Because of this, if you fall into a high-risk category based on age and risk factors, it’s worth discussing screening tests with your doctor even if you feel fine.

Diagnostic Methods

When you visit your doctor with concerns about peripheral ischaemia, they will begin with a thorough physical examination. During this exam, your doctor will check the pulses in your legs and feet by feeling for them with their fingers. Weak or absent pulses can be an important clue that blood flow is reduced^[10]. They will also use a stethoscope to listen for a bruit, which is a whooshing sound in the arteries of your legs. This sound occurs when blood flows through a narrowed artery and can indicate blockages^[11].

Your doctor will carefully examine the skin on your legs and feet, looking for changes in color, temperature, texture, or the presence of wounds or ulcers. They’ll check for hair loss on your legs, changes in toenail thickness, and any signs of muscle wasting. They may also perform a neurological examination to assess sensation and movement in your affected limbs^[12].

Ankle-Brachial Index (ABI)

The most important initial test for diagnosing peripheral ischaemia is called the ankle-brachial index or ABI. This test is simple, painless, and provides valuable information about blood flow in your legs. During the test, a healthcare provider measures the blood pressure in your arm and compares it to the blood pressure in your ankle^[13].

To perform the test, a blood pressure cuff is placed on your arm and another on your ankle. The provider uses a special ultrasound device called a Doppler to detect blood flow and measure the pressure. The ankle pressure is then divided by the arm pressure to calculate the ABI. A difference between the two measurements may indicate peripheral ischaemia^[14].

Current guidelines recommend ABI testing for patients with a history or examination findings that suggest peripheral ischaemia. However, routine ABI screening is not recommended for people who don’t have symptoms and aren’t at increased risk, as testing those at low risk doesn’t provide much benefit^[15].

Exercise ABI Testing

Some people have symptoms of peripheral ischaemia but show normal results on a resting ABI test. For these individuals, an exercise ABI test can provide more information. This test involves measuring your ABI before and after you walk on a treadmill or perform other exercises^[16].

The exercise test can reveal problems that don’t show up when you’re at rest because your muscles need more blood flow during activity. If the ABI drops significantly after exercise, this suggests that your arteries cannot provide enough blood to meet your muscles’ increased demands, confirming the diagnosis of peripheral ischaemia^[17].

Imaging Tests

If your ABI test is abnormal or if your doctor needs more detailed information about the location and severity of blockages, they may order imaging tests. These tests create pictures of your blood vessels and help identify exactly where narrowing or blockages are located.

Doppler ultrasound is a type of ultrasound that can measure both the direction and speed of blood flow through your vessels. It’s a non-invasive test that uses sound waves to create images and doesn’t involve radiation or needles^[18].

CT angiography is an advanced X-ray procedure that uses a computer to generate three-dimensional images of your blood vessels. Before the scan, you receive an injection of a special dye called contrast material, which makes your blood vessels visible on the images^[19].

Magnetic resonance angiography, or MR angiography, uses radiofrequency waves in a strong magnetic field to create detailed images of your blood vessels. A computer measures the energy released by your body and uses this information to construct two- and three-dimensional pictures. This test doesn’t use radiation^[20].

Angiogram, also called arteriography, is an X-ray study of the blood vessels taken using contrast dyes. During this procedure, a thin tube called a catheter is inserted into an artery, usually in your groin. The catheter is guided to the area being studied, and contrast dye is injected. X-rays are then taken to show the flow of dye through your arteries, revealing any narrowing or blockages^[21].

Blood Tests

While blood tests don’t directly diagnose peripheral ischaemia, they are important for identifying underlying conditions that contribute to the disease. Your doctor will likely order tests to check your cholesterol levels, blood sugar levels (to screen for or monitor diabetes), and kidney function. High levels of LDL cholesterol (the “bad” cholesterol) or low levels of HDL cholesterol (the “good” cholesterol) increase your risk of atherosclerosis, which causes peripheral ischaemia^[22].

Diagnostics for Clinical Trial Qualification

Clinical trials testing new treatments for peripheral ischaemia use specific diagnostic criteria to determine who can participate. These trials need to ensure that participants actually have the condition and that it’s severe enough to potentially benefit from the treatment being studied.

For enrollment in clinical trials, the ankle-brachial index remains a key diagnostic tool. Researchers typically require participants to have an ABI below a certain threshold to confirm the presence of peripheral ischaemia. The specific ABI cutoff may vary depending on the trial, but values below 0.90 are generally considered abnormal^[23].

Clinical trials may also require imaging studies such as angiography to document the exact location and extent of arterial blockages. This information helps researchers understand which participants might respond best to specific interventions and allows them to measure whether treatments successfully improve blood flow to blocked areas^[24].

For trials focused on advanced disease, participants may need to meet criteria for critical limb ischemia, which is the most severe form of peripheral ischaemia. This diagnosis is based on specific symptoms such as severe pain in the legs and feet while resting, or the presence of non-healing wounds or tissue death (gangrene) on the feet or legs. Diagnostic tests may include measurements showing very low blood pressure in the ankle (typically less than 50 mm Hg) or very low toe pressure^[25].

Some clinical trials may use additional tests to assess how well blood flows to specific areas of tissue. These can include measurements of oxygen levels in the skin or other specialized assessments that help determine the severity of ischemia. Researchers want to ensure they’re studying patients who have significant disease but are still early enough in the condition’s progression that treatment could make a meaningful difference^[26].

⚠️ Important

Participating in a clinical trial may give you access to new treatments before they become widely available, but it’s important to understand that experimental treatments may not work and could have unknown side effects. Talk carefully with your doctor and the research team about the potential benefits and risks before deciding whether to participate in a trial.

Prognosis and Survival Rate

Prognosis

The outlook for people with peripheral ischaemia varies greatly depending on how early the condition is diagnosed and how well risk factors are managed. With proper treatment, including lifestyle changes and medications, most people’s symptoms remain stable and some may even experience improvement in their pain^[27]. The condition is treatable, especially when caught early, and many people can maintain an active lifestyle with appropriate care^[28].

However, peripheral ischaemia is more than just a leg problem. It’s actually a marker that indicates atherosclerosis throughout your body. People with peripheral ischaemia have an equivalent cardiovascular risk to those who have previously had a heart attack. This means they face increased chances of heart attack, stroke, and other serious cardiovascular events^[29]. The majority of patients with peripheral ischaemia also have clinically significant coronary artery disease or cerebrovascular disease affecting the brain^[30].

If peripheral ischaemia progresses to the most severe stage called critical limb ischemia, the prognosis becomes much more serious. This severe form causes intense pain at rest and non-healing wounds, dramatically increasing the risk of major medical complications^[31].

Survival Rate

Within one year of developing critical limb ischemia, about 1 in 4 people die, most commonly from heart disease or stroke. Almost 1 in 3 people require amputation of the affected limb^[32]. The mortality rate for those with critical limb ischemia can exceed 50%, which is higher than many cardiovascular diseases^[33]. Studies have shown that amputation rates for those diagnosed with critical limb ischemia can reach 40%^[34].

Among people with peripheral ischaemia who smoke, cardiovascular mortality rates are more than double that of those who have never smoked. This underscores how important it is to quit smoking if you have this condition^[35]. Having low HDL cholesterol (less than 40 mg per dL in men and less than 50 mg per dL in women) is also associated with increased risk of death in people with peripheral ischaemia^[36].

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