Approach

Peripheral arterial disease (PAD) is often under-recognised and under-treated.[3][9]​ Many patients with PAD are asymptomatic, but will have 1 or more risk factors.[2][3]​ The resting ankle-brachial index (ABI) is the initial diagnostic test for PAD.[2] It is recommended in all patients with suspected lower limb disease with a history of exertional leg symptoms, non-healing wounds/foot ulcers, or abnormal lower extremity pulse examination. The toe brachial index (TBI) is useful in those patients where the ABI is unreliable (e.g., non-compressible arteries in patients with diabetes and advancing age, as well as in many renal patients on dialysis). Other tests used to establish diagnosis include:[2][44]

  • Segmental pressure examination

  • Duplex ultrasound

  • Pulse volume recording

  • Continuous wave Doppler ultrasound

  • Exercise ABI

  • Computed tomography angiography (CTA)

  • Magnetic resonance angiography (MRA)

  • Angiography

Patients at risk

Classic claudication symptoms occur in a minority of patients and it is reasonable to measure the ABI in people at increased risk of PAD but who have no history or physical examination. This includes people:[2]

  • Aged 65 years or older

  • Aged 50-64 years with risk factors for atherosclerosis (e.g., diabetes mellitus, history of smoking, hyperlipidaemia, hypertension) or a family history of PAD

  • Who are less than 50 years old with diabetes mellitus and one additional risk factor for atherosclerosis

  • With known atherosclerotic disease in another vascular bed (e.g., coronary, carotid, subclavian, renal, mesenteric artery stenosis, or abdominal aortic aneurysm).

Other symptoms and signs

Further symptoms and signs may lead to a diagnosis of PAD in the presence of risk factors:

  • Calf or foot cramping with walking that is relieved with rest

  • Thigh or buttock pain with walking that is relieved with rest

  • Erectile dysfunction

  • Pain worse in one leg

  • Diminished pulse.

Critical limb ischaemia should be suspected with the following:

  • Foot pain at rest

  • Gangrene

  • Non-healing wound/foot ulcer

  • Muscle atrophy

  • Dependent rubor

  • Pallor when the leg is elevated

  • Loss of hair over the dorsum of the foot

  • Thickened toenails

  • Shiny/scaly skin.

Acute limb ischaemia should be suspected with the following:[2]

  • The classic 6 signs of acute limb ischaemia, which are pain, paralysis, paraesthesias, pulselessness, poikilothermia, and pallor

  • Symptom duration less than 2 weeks.

Ankle-brachial index

An ABI should be performed in patients who have symptoms or answered positively to a review of questions regarding PAD.[45] An ABI ≤0.9 is diagnostic for the presence of PAD. The resting ABI should be used to establish the diagnosis of PAD in patients with exertional low-extremity claudication, rest pain, chronic limb ischaemia, or non-healing wounds/foot ulcers. It is an inexpensive and rapid surgery-based test.[2][3]​ ABI is performed by measuring the systolic pressure of the left and right brachial arteries and the left and right posterior tibial and dorsalis pedis arteries pressure. The ABI is the highest of the dorsalis pedis and posterior tibial arteries' pressure divided by the higher of the left and right arm brachial artery pulse pressure.

ABI may not be accurate in patients with non-compressible arteries, such as those with comorbid diabetes mellitus or chronic kidney disease (CKD), particularly those on dialysis. Patients with either severely stenotic or totally occluded arteries may also have normal ABI if there is abundant collateral system present.[45] Diagnosis of PAD should not be excluded based on normal or raised ankle-brachial pressure index alone in people with diabetes or CKD.[2][46] The ABI is a marker of peripheral atherosclerosis, as well as a predictor of vascular events.[47]

Toe-brachial index

A TBI should be used to establish the diagnosis of PAD in patients in whom lower extremity PAD is clinically suspected, but in whom the ABI test is not reliable due to non-compressible vessels, such as in patients with comorbid diabetes or CKD, or those with advanced age. TBI should also be measured to diagnose patients with suspected PAD when the resting ABI is >1.40.[2]

Additional tests to help diagnose PAD

Evaluation of the arterial pressure waveform using pulse volume recording via pneumoplethysmography can add valuable information to the isolated ABI, particularly if the ABI is falsely elevated. Exercise ABIs are also a valuable adjunct. An exercise ABI does not provide information about the location of the lesion. It is useful, however, in establishing the diagnosis of lower extremity PAD in symptomatic patients when resting ABIs are normal or borderline.[2] Walking limitations can be measured with exercise ABI, along with the onset of symptoms, recovery time, and the total walking time.

Location and severity of PAD, using continuous wave Doppler ultrasound, is measured through a decrease in pulsatility index between adjacent proximal and distal anatomical segments.

Pulsatility index is calculated as Vmax - Vmin/Vmean, where:

  • Vmax = peak systolic velocity

  • Vmin = minimum diastolic velocity

  • Vmean = mean blood flow velocity.

Location and magnitude of stenosis can be determined with segmental pressure examination, based on pressure gradients between adjacent segments. Segmental pressure measurement may be artifactually elevated in patients with non-compressible arteries.

Further tests

Depending on the patient's symptoms, other diagnostic tests may be needed, including a more thorough assessment of the lower-extremity vasculature.[2][3] If the ABI/TBI is abnormal and symptoms warrant revascularisation, the next test to guide the therapeutic decision is duplex ultrasonography of the lower-extremity arteries.[48] The duplex ultrasound is cost-effective and non-invasive, and should be done first to verify stenoses. This is most useful for counselling patients who may not have a minimally-invasive option to treat mild or moderate claudication.

Computed tomography angiography (CTA), magnetic resonance angiography (MRA), and catheter angiography can provide the anatomical detail necessary to determine a revascularisation strategy and are appropriate initial investigations for patients presenting with acute limb ischaemia but require intravenous contrast.[49]​ The spatial resolution of CTA and MRA may be lower than digital subtraction angiography.

  • The location and degree of stenosis can also be assessed by duplex ultrasound. This is the preferred and most widely used modality to assess stenoses.[48] The accuracy is diminished in tortuous, calcified prosthetic bypass grafts, and in vessels with multiple stenoses. In the aortoiliac arterial segment, accuracy can also be diminished due to bowel gas and body habitus.

  • Visualisation of tissue surrounding the artery using CTA can demonstrate stenosis due to aneurysms, popliteal entrapment, or cystic adventitial disease that cannot be detected by angiography.

  • Revascularisation can occur at the same time as catheter angiography. It is the only accepted modality and is considered the investigation of choice for assessing vascular anatomy and stenosis.

  • Anatomical location and stenosis can be diagnosed using MRA, although patients with pacemakers, defibrillators, and some cerebral aneurysm clips cannot be scanned safely. Gadolinium has caused nephrogenic systemic fibrosis in patients with chronic renal insufficiency.

Evaluation for comorbidities and risk enhancers

The presence of specific comorbidities and risk factors increases the risk for major adverse cardiovascular events and major adverse limb events in those with PAD, which may affect management choices. Evaluation of patients with PAD should include assessment for:[2]

  • Hypertension

  • Dyslipidaemia

  • Diabetes

  • CKD/end-stage renal disease

  • Depression

  • Atherosclerotic disease in more than one vascular bed (PAD, coronary artery disease, cerebrovascular disease)

  • Microvascular disease (retinopathy, neuropathy, nephropathy)

  • Current smoking/tobacco use

  • Older age and geriatric syndromes (frailty, mobility impairment, sarcopenia, malnutrition)

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