Peripheral Arterial Disease

Introduction

Peripheral arterial disease is atherosclerotic obstruction of the arteries supplying the limbs. It affects an estimated 20% of people over 60 in the UK, though only a quarter of those have symptoms, and it is substantially underdiagnosed because patients attribute a reduced walking distance to age or arthritis.

The topic is best learned as a spectrum defined by whether the ischaemia is present only on exertion or also at rest.

The older term critical limb ischaemia has largely been replaced by chronic limb-threatening ischaemia (CLTI), which better reflects that limb loss is driven by a combination of perfusion, wound extent and infection rather than by a single pressure threshold.

Pathophysiology and anatomy

The underlying process is atherosclerosis, identical to that in the coronary and cerebral circulations, which is why peripheral arterial disease is above all a marker of systemic vascular risk. Plaque forms preferentially at bifurcations and points of tethering, where flow is turbulent.

Symptoms appear when a stenosis limits the rise in blood flow needed for exercising muscle. At rest a moderately stenosed artery delivers adequate flow; on walking, oxygen demand rises several-fold, supply cannot follow, and anaerobic metabolism produces the cramping pain of claudication. Rest pain develops only when perfusion is inadequate even for basal metabolic requirements, which is usually when the disease is multilevel.

As a rule of thumb, the pain is felt one level below the occlusion, because it arises in the muscle group supplied beyond the block.

Risk factors

• Smoking - the strongest risk factor, increasing risk three to four fold and the one most strongly linked to progression and to graft failure. Roughly 80 to 90% of patients with claudication are current or former smokers.
• Diabetes mellitus - increases risk two to four fold, produces distal tibial disease, and combines with neuropathy so that patients present late with painless ulceration
• Hypertension
• Dyslipidaemia, particularly raised LDL cholesterol and low HDL
• Increasing age and male sex
• Chronic kidney disease, which also causes medial arterial calcification and an artefactually high ABPI
• Family history and known atherosclerosis elsewhere - coronary or cerebrovascular disease
• Hyperhomocysteinaemia and raised fibrinogen, and inflammatory conditions

Clinical features

Intermittent claudication

• Cramping, aching pain in a muscle group brought on by walking
• A reproducible claudication distance - the same distance produces the same pain each time, and it is shorter uphill or hurrying
• Relieved by two to five minutes of standing still, without needing to sit or bend forward
• Recurs at the same distance on resuming walking
• The patient may describe having to stop and look in shop windows, which is where the historical name window-shopper's disease comes from

Chronic limb-threatening ischaemia

• Rest pain, typically burning pain in the forefoot and toes, worse at night when the leg is elevated in bed and cardiac output falls
• Relieved by hanging the leg out of bed or sleeping in a chair - because gravity augments perfusion pressure. Ask this question directly; it is close to diagnostic.
• Arterial ulcers - punched out, with a sharply demarcated edge, a pale or necrotic base with little granulation, situated over pressure points, the tips of the toes, the heel and the lateral malleolus. They are painful, unlike neuropathic ulcers.
• Gangrene, dry or wet
• Chronic changes - hairless, shiny, cool skin, thickened brittle nails, muscle wasting, and slow capillary refill

Examination

1. Inspect both legs fully, including between the toes and the heels, for ulcers, gangrene, pallor, hair loss and trophic changes
2. Palpate temperature and capillary refill, comparing sides
3. Palpate all pulses - femoral, popliteal, posterior tibial and dorsalis pedis - and listen for femoral and aortic bruits
4. Buerger test - elevate the leg and note the angle at which it becomes pale (the Buerger angle; below 20 degrees indicates severe ischaemia), then hang it over the side of the couch and watch for the reactive hyperaemia that produces a dusky red foot
5. Assess sensation and motor function, both for diabetic neuropathy and to detect the sensorimotor deficit of acute ischaemia
6. Cardiovascular examination - blood pressure, heart rhythm for atrial fibrillation, carotid bruits, and abdominal palpation for an aneurysm
7. Measure the ABPI

The ankle-brachial pressure index

The ABPI is the highest systolic pressure at the ankle in that leg, divided by the highest brachial systolic pressure of the two arms, measured with a hand-held Doppler probe. It is the key bedside investigation and it is worth being able to describe how to perform it.

Differential diagnosis

Also consider popliteal artery entrapment syndrome and cystic adventitial disease in a young patient with claudication and no risk factors, Buerger disease (thromboangiitis obliterans) in a young heavy smoker with distal ischaemia and superficial thrombophlebitis, and simple musculoskeletal or arthritic pain, which is not reproducible by distance.

Investigations

• ABPI, at rest and after exercise if needed
• Duplex ultrasound - the first-line imaging test. It is non-invasive, gives anatomical and haemodynamic information, and identifies the level and severity of stenoses.
• CT angiography or MR angiography - reserved for planning revascularisation, defining run-off vessels and assessing the aortoiliac segment
• Digital subtraction angiography - now largely a therapeutic procedure performed at the time of angioplasty
• Blood tests - FBC (anaemia and polycythaemia both worsen ischaemia), U&Es, HbA1c, lipid profile, and thrombophilia or vasculitis screen in young patients with no risk factors
• ECG and cardiovascular assessment, since coexisting coronary disease is the rule rather than the exception
• Wound swabs and imaging for osteomyelitis where there is an infected ulcer, with plain radiographs and MRI

Management

Secondary prevention in every patient

This is the part that changes mortality, and it applies whether or not the leg is treated.¹

• Smoking cessation - the single most important intervention, with pharmacological support and referral to a cessation service
• A high-intensity statin, atorvastatin 80 mg daily, for secondary prevention of cardiovascular disease²
• Antiplatelet therapy - NICE recommends clopidogrel 75 mg as first line in peripheral arterial disease, with aspirin if clopidogrel is unsuitable
• Blood pressure control to target, and optimisation of diabetes
• Weight management and a structured exercise habit
• Foot care - daily inspection, well-fitting footwear, podiatry review, and prompt attention to any break in the skin. In diabetic patients this should be formalised as part of annual foot screening.

Treating intermittent claudication

1. A supervised exercise programme is first line. NICE recommends offering two hours of supervised exercise a week for three months, with patients encouraged to exercise to the point of maximal pain. It works by promoting collateral formation, improving muscle metabolic efficiency and endothelial function, and typically improves walking distance by 50 to 200% - comparable to angioplasty at one year and considerably cheaper.¹
2. Naftidrofuryl oxalate may be considered where supervised exercise has not helped and the patient does not want revascularisation, with review at three to six months and discontinuation if there is no benefit
3. Angioplasty with or without a stent is offered when exercise has failed, symptoms are lifestyle-limiting, and imaging shows suitable disease. It is most effective for short, focal, iliac and proximal femoral lesions.
4. Bypass surgery - femoropopliteal or femorodistal bypass, preferably using autologous vein (usually reversed or in situ great saphenous vein), which has better patency than a prosthetic graft below the knee. Reserved for extensive disease unsuitable for angioplasty.
5. Do not offer revascularisation for asymptomatic disease or mild claudication, since the risks outweigh the benefit

Chronic limb-threatening ischaemia

This is a different problem: the aim shifts from improving walking distance to saving the limb and relieving pain. Refer urgently to vascular surgery.

• Analgesia, which usually requires opioids, and often neuropathic agents in addition
• Revascularisation wherever technically possible - angioplasty or bypass, guided by the anatomy and the patient's fitness. The BASIL trials suggested that bypass with vein is preferable where a patient is expected to survive more than two years, and angioplasty where they are not.³
• Wound care and offloading, with a multidisciplinary diabetic foot team where relevant
• Treat infection promptly with antibiotics, and drain or debride collections urgently
• Amputation where the limb is not salvageable, where sepsis is uncontrolled, or where a painful non-functional limb is worse than a prosthesis. This should be a considered multidisciplinary decision with the patient, including rehabilitation planning, not a failure.
• Palliative approach in patients unfit for intervention - pain control, wound management and honest discussion about prognosis

Complications

• Progression to chronic limb-threatening ischaemia, which occurs in around 1 to 2% of claudicants per year
• Acute limb ischaemia from thrombosis on an existing plaque or from embolus
• Non-healing ulceration, infection, osteomyelitis and gangrene
• Major amputation, with all its functional, psychological and mortality consequences
• Myocardial infarction and stroke - the commonest causes of death in this population by a wide margin
• Graft failure, restenosis and the need for repeat intervention
• Reduced mobility, falls, deconditioning and depression, which are consistently underestimated

Red flags

Prognosis

For the leg, the outlook in claudication is more benign than patients fear. Around three quarters remain stable or improve with exercise and risk factor modification, and only about 1 to 2% per year progress to limb-threatening ischaemia. Reassurance on this point is a legitimate and useful part of the consultation.

For the patient, the outlook is considerably worse. Claudication identifies a person with advanced systemic atherosclerosis, and roughly 20% will have a non-fatal cardiovascular event within five years and 30% will be dead, almost always from myocardial infarction or stroke rather than from anything to do with the leg. A patient with chronic limb-threatening ischaemia has a five-year mortality approaching 50%, which is worse than many common cancers.

This asymmetry is the single most important message of the topic. The leg is a window on the coronary arteries, and the intervention that most extends a claudicant's life is not an angioplasty but a statin, an antiplatelet and stopping smoking.