Peripheral Vascular Disease

Synonym: peripheral arterial disease

Peripheral vascular disease occurs when there is significant narrowing of arteries distal to the arch of the aorta, most often due to atherosclerosis. Symptoms vary from calf pain on exercise (intermittent claudication) to rest pain (critical limb ischaemia), skin ulceration, and gangrene. Patients diagnosed as having peripheral vascular disease, including those who are asymptomatic, have an increased risk of mortality, myocardial infarction and stroke.¹

• Chronic limb ischaemia is almost always caused by atherosclerosis of the peripheral arteries.
• Prevalence increases with age: when measured by non-invasive tests, is about 3% in people under the age of 60 years but rises to over 20% in people over 75 years. Only a quarter of those affected have symptoms.²
• It is more common in men than women.

Risk factors³

• Smoking
• Diabetes mellitus
• Hypertension
• Hyperlipidaemia
• Physical inactivity
• Obesity

• The most common symptom is muscle pain in the lower limbs on exercise (intermittent claudication):⁴
  • Severe cramping pain and weakness in the calf and/or buttocks on walking. The onset of pain is usually gradual and occurs at a fixed distance walked before it recurs.
  • The pain usually disappears when standing still.
  • Pain comes on more rapidly when walking uphill than on the flat.
  • Claudication can occur in both legs but is often worse in one leg.
  • Similar pain may occur in buttocks and thighs associated with absent femoral pulses and male impotence (Leriche's syndrome; caused by aorto-iliac obstruction).
• Ischaemic rest pain:
  • Severe, extensive peripheral vascular disease can lead to a severe unremitting pain in the foot, particularly at night.
  • It is partially relieved by hanging the foot out of the bed.

The Edinburgh Claudication Questionnaire is very specific and sensitive.^4,5

Signs

A full cardiovascular history and examination is essential.

• Examination of the affected limb(s) reveals absent pulsation and sometimes the leg is pale, cold and with a loss of hair.
• Examination usually reveals weak or absent pulses.
• Patients with severe peripheral vascular disease or critical lower limb ischaemia may have ulceration or gangrene.
• Examination must include the whole cardiovascular system, including the abdomen for possible aortic aneurysm.

The differential diagnosis of pain in the lower limb when walking includes sciatica and spinal stenosis, deep vein thrombosis, entrapment syndromes and muscle/tendon injury.

Adverse/risk factors

Any patient suspected or diagnosed as having peripheral vascular disease should have a full cardiovascular risk assessment.¹

• Blood pressure.
• Full blood count (anaemia will aggravate peripheral vascular disease), ESR (inflammatory process, e.g. giant cell arteritis), thrombophilia screen.
• Fasting blood glucose.
• Lipid levels.
• ECG: 60% of patients with intermittent claudication have ECG evidence of pre-existing coronary heart disease.

Confirm diagnosis

• The main method to confirm the diagnosis is Doppler ultrasonography (duplex scanning). The ratio of systolic blood pressure at the ankle and in the arm - ankle-brachial pressure index (ABPI) - provides a measure of blood flow at the level of the ankle (as a general guide, normal = 1, claudication 0.9-0.6, rest pain 0.3-0.6, impending gangrene 0.3 or less). Duplex ultrasonography is also able to determine the site of disease and indicate the degree of stenosis and length of an occlusion.
• Other methods of investigation now include magnetic resonance angiography and computed tomography angiography.¹
• Digital subtraction arteriography is not recommended as the primary imaging modality and is essentially a pre-operative investigation. Its use is limited to an adjuvant of endovascular management, surgical planning or the management of an acute ischaemic limb.

• Coronary heart disease: Because of the probability of significant coronary artery disease, patients who require vascular surgery to the lower limb(s) may need coronary artery revascularisation as a prelude.
• Cerebrovascular disease.
• Up to 20% of patients with intermittent claudication have diabetes.

• Patients with suspected peripheral vascular disease should be referred to secondary care if:¹
• There is any doubt about the diagnosis or there is concern that the symptoms may have an unusual cause.
• Risk factors can't be managed to recommended targets.
• The patient has symptoms which limit lifestyle and objective signs of arterial disease.
• Young and otherwise healthy adults, presenting prematurely with claudication, should be referred to exclude entrapment syndromes and other rare disorders.

Initial management should consist of modification of all cardiovascular risk factors in order to reduce the risk of critical limb ischaemia and improve the patient's functional status. Most patients' symptoms improve with optimal medical treatment and invasive intervention is often not required.⁴

• Smoking cessation.
• Promote regular exercise: walking through discomfort is not damaging and promotes the collateral circulation leading to an improvement in walking capacity.
• Weight reduction for patients who are overweight or obese.
• Antiplatelet therapy is recommended for those with symptomatic peripheral vascular disease.
  • The antiplatelet agents aspirin, clopidogrel, aspirin plus dipyridamole, have been shown to reduce major cardiovascular events. Antiplatelet agents reduce vascular death in patients with any manifestation of atherosclerotic disease by about 25%.⁶
  • Clopidogrel alone is recommended for people who are intolerant of low-dose aspirin and either have experienced an occlusive vascular event or have symptomatic peripheral vascular disease.⁷
  • Clopidogrel is at least as effective as aspirin in patients with peripheral vascular disease and has a better side-effect profile. However, it is much more expensive and is generally reserved for those who cannot take or tolerate aspirin or who continue to have events on aspirin.
• Management of diabetes mellitus: optimal control of glucose and all other cardiovascular risk factors.
• Hypertension: long-term benefit but in the short-term a reduction in blood pressure, whatever drug treatment has been used, may worsen intermittent claudication.⁴
• ACE inhibitors (ramipril in the HOPE study⁸) have been shown to reduce cardiovascular morbidity and mortality in patients with peripheral vascular disease by about 25%. This reduced risk is greater than that just due to blood pressure control.
• Reduction in cholesterol: lowering total cholesterol and low-density lipoprotein cholesterol by 25% with a statin reduces cardiovascular mortality and morbidity in patients with peripheral vascular disease by around a quarter.⁹ Lipid lowering therapy with a statin is recommended, aiming to maintain total cholesterol level below 3.5 mmol/l.¹
• Peripheral vasodilators:¹⁰
  • Naftidrofuryl may alleviate symptoms and improve pain-free walking distance in moderate disease, but it is not known whether there is any effect on the outcome of the disease.
  • Cilostazol has been shown to increase walking distance significantly in people with claudication.¹¹ The precise role of cilostazol remains uncertain. Cilostazol is licensed for use in intermittent claudication to improve walking distance in patients without peripheral tissue necrosis and who do not have pain at rest.
  • Inositol nicotinate, pentoxifylline and cinnarizine are not established as being effective.
• Elevated plasma levels of homocysteine (hyperhomocysteinaemia) are increasingly recognised as a potential risk for atherothrombotic vascular diseases.¹² There is currently insufficient evidence to support the treatment of hyperhomocysteinaemia with folate and B₁₂.

Surgical

• Two options are percutaneous angioplasty and bypass surgery. Indications for surgical intervention in peripheral vascular disease include: disabling claudication, critical limb ischaemia (urgent referral recommended) or weak or absent femoral pulses. Percutaneous transluminal angioplasty has only a transient benefit and there is no clear evidence of long-term benefit of bypass surgery.
• Bypass surgery is performed only infrequently for intermittent claudication because, even though symptoms are frequently unilateral, most people with claudication have bilateral disease and revascularising one leg often unmasks previously asymptomatic disease in the other leg.
• No convincing evidence supports the use of percutaneous balloon angioplasty or stenting in patients with intermittent claudication. Although percutaneous balloon angioplasty may lead to a short term (six months) improvement in walking distance, in the longer term (two years) optimal medical management, as outlined above, is better than percutaneous balloon angioplasty in terms of walking distance and quality of life.⁴
• The threshold for percutaneous balloon angioplasty, stenting, and surgery is lower in patients who have predominantly aorto-iliac (suprainguinal) disease. Because these patients seem to benefit less from optimal medical management, percutaneous balloon angioplasty and stenting in the aorta or iliac arteries is more durable than that below the inguinal ligament and aorto-iliac reconstruction deals with both legs at the same time.
• Ischaemic rest pain: requires urgent referral to a specialist vascular unit. About 90% of patients with ischaemic rest pain can be successfully treated by balloon angioplasty or surgical revascularisation. However, about 10% of patients will require an amputation (usually below the knee). Amputation is most likely to be necessary in those patients who continue to smoke.

• Acute limb ischaemia may result from thrombosis arising within a peripheral artery or from embolic occlusion.
• Infection and poor healing of tissue with reduced blood supply.
• Gangrene.
• Amputation: in the Framingham Heart Study, only 1.6% of patients with claudication reached the amputation stage after 8.3 years of follow-up.¹³

• Very variable: Intermittent claudication may resolve spontaneously, remain stable or progress rapidly to critical limb ischaemia. About 15% of people with intermittent claudication eventually develop critical leg ischaemia, which endangers the viability of the limb.
• Coronary heart disease is the major cause of death in people with peripheral vascular disease. The mortality rate, mainly from coronary and cerebrovascular events, is three to four times greater than age-sex matched controls without claudication. The risk is similarly increased in those who have asymptomatic disease as well as those with intermittent claudication.¹⁴
• Outcome for patients presenting with intermittent claudication over five years:⁴
  • 50% will improve, 25% will stabilise and 25% will worsen. Of those who worsen, 20% (5% of total) will need intervention and 8% (2% of total) will need a major limb amputation.
  • 5-10% will have a non-fatal cardiovascular event.
  • 30% will die: cardiac 16%, cerebral 4%, other vascular 3%, non-vascular 7%.
  • 55-60% will survive with no cardiovascular event.

See separate article: Primary Prevention of Cardiovascular Disease.