Peripheral arterial disease (PAD) is an atherosclerotic process that leads to significant arterial narrowing or blockage of the arteries supplying the lower limbs below the level of the renal arteries. It does not include coronary and intracranial vessels. It is frequently underdiagnosed and often subject to suboptimal care.
PAD is extremely common and has an estimated worldwide prevalence of almost 10%, increasing to 15-20% in people above 70 years of age.1,2 However, only 25% of these patients have symptoms.
The following are risk factors for PAD:
- Age. Incidence and prevalence of PAD increase with age.
- Sex. Men are more likely to develop PAD. The male:female ratio is 2:1 for PAD and 3:1 for critical limb ischaemia (CLI).
- Ethnicity. Black ethnicity is an independent risk factor.
- Obesity and poor exercise. Increased body mass is associated with an increased atherosclerotic burden.
- Smoking. This is the most important modifiable risk factor for developing PAD and the link between the two may be even stronger than that between coronary artery disease and smoking.3 Smokers are four times more likely to develop intermittent claudication (IC). Stopping smoking can reduce the cardiovascular risk by 50% within one year. The failure rate of surgical bypass graft is three times higher in those who continue to smoke.4
- Diabetes. Patients with diabetes are twice as likely to develop PAD and disease progresses more rapidly in them.3The amputation rate is five to 10 times higher in patients with diabetes. A 1% increase in HbA1c is associated with a 26% increase in risk of developing PAD.5
- Hypertension. BP >160/95mmHg increases the risk of developing IC. The increase is fourfold in females and two- to fivefold in males.
- Hyperlipidaemia. Fasting cholesterol >7mmol/L doubles the risk of developing IC. Data from the Framingham Heart Study confirmed that high BP and high cholesterol are both independent risk factors.6
- Chronic renal insufficiency, and raised haematocrit and homocysteine are linked to increased risk of PAD, but the mechanism is unclear.
PAD increases the risk of all-cause mortality.7 Data from the REACH registry give a good indication of the risk of a vascular event in patients with PAD. The REACH trial recorded 55,499 patients; those recruited to the trial with PAD had the highest three-year event rate of MI/stroke/death/hospitalisation (40.4%).7
PAD is a spectrum of disease, from being asymptomatic to symptoms of IC, CLI and limb amputation. It is a strong indicator of cardiovascular risk, so prompt diagnosis is important. Even asymptomatic PAD has a risk of cardiovascular and cerebrovascular events. Increasing awareness of the disease helps to identify these patients at an early stage. Diagnosis is made on clinical symptoms, examination and ankle-brachial pressure index (ABPI) measurement.
IC is a common symptom characterised by cramp-like pain in the leg, precipitated by walking or exercising, which rapidly stops by resting, only to return on resumption of walking or exercising.
The muscle group affected depends on the level of arterial disease (table 1). The distance at which the pain limits mobility is called claudication distance. Patients with IC are four times more likely to die from stroke or MI. Pain at rest or at night can indicate CLI. Waking with pain when lying in bed, requiring the patient to hang their leg out of bed or walk around, is due to poor blood flow velocity.
CLI is a severe manifestation of PAD characterised by rest pain, ulceration, tissue loss or gangrene. For every 100 patients with IC, approximately one to two a year will develop CLI;8 50% of those with CLI die within two years.
|Table 1. Symptoms associated with level of disease|
|Level of disease||Symptoms|
|Internal Iliac||Buttock claudication|
|External iliac||Calf and thigh claudication|
|Aortic||Bilateral buttock and thigh claudication|
A general assessment is essential, including BP, BMI and abdominal palpation to exclude aortic aneurysm. A thorough limb examination should be performed, including:
- Inspection for hair loss, discoloration of toes, ulcer, gangrene
- Palpation for difference in temperature; check femoral, popliteal, posterior tibial (PT) and dorsalis pedis (DP)
Remember the six Ps of acute leg ischaemia:
- Paralysis of abrupt onset
- Perishing with cold (poikilothermia)
Acute leg ischaemia is associated with an amputation rate of 13% and a mortality rate of 10%. Both are increased by delayed diagnosis and treatment.9
ABPI measurement is a quick, non-invasive, powerful tool in the assessment of PAD, which should be carried out by somebody trained in the procedure. ABPI quantifies the severity of arterial occlusion in the leg. It is 95% sensitive and 100% specific.
It has its limitations in patients with diabetes or endstage renal disease, and heavy smokers, because calcified arteries can give a false high reading. Aortoiliac stenosis with rich collateral network can give a normal ABPI reading.
How to perform the ABPI test
Make sure the patient is lying flat and rested for 15-20 minutes.
- Approximately 2cm above the malleoli, apply a standard 15cm cuff (for a large leg, a larger cuff is needed)
- Detect the DP and PT pulses
- Apply ultrasound gel over the first pulse
- Position the probe at an angle of 45-60 degrees and identify the pulse
- Inflate the cuff until you hear no signal
- Start deflating the cuff until you hear the first signal – the systolic pressure
- Measure the systolic BP of the brachial artery (bilaterally)
- The higher of the two pressures from the DP and the PT pulses is taken as the numerator and the higher of the two brachial pressures as the denominator
Normal ABPI is 0.9-1.2 in the supine position (table 2). In the presence of typical symptoms of PAD, a normal ABPI does not exclude PAD. In this situation, the ABPI measurement should be repeated after treadmill exercise testing.
|Table 2. ABPI interpretation|
|>1.2||Abnormal vessel hardening||Modify cardiovascular risks|
|<0.9||PAD||Modify cardiovascular risks
Refer if meets criteria
Recommended blood tests
- FBC to exclude anaemia, polycythaemia and thrombocythaemia
- Serum urea and creatinine (U&Es)
- Fasting cholesterol
- For patients aged under 50 years, thrombophilia screen and serum homocysteine10
The role of primary care
All patients with PAD should be offered advice, support and treatment with respect to the secondary prevention of cardiovascular disease as recommended by NICE.11 The following are important aspects of primary care management:
- Weight loss and exercise. NICE recommends that all patients with IC should be offered a supervised exercise programme.11
- Smoking cessation. This is extremely important and should be treated aggressively as recommended by NICE guidelines.
- Target BP. Some 55% of patients with PAD have hypertension. Target systolic BP less than 130mmHg and diastolic BP less than 80mmHg with appropriate therapy this reduces stroke risk by 38% and cardiovascular death by 14%
- Target HbA1c in patients with diabetes. These patients have a worse prognosis in terms of progression to CLI and increased risk of lower limb amputation.
- Target hyperlipidaemia and statin therapy. Total cholesterol <4mmol/L, LDL <2mmol/L. In the Heart Protection Study, a 17.6% reduction in cardiovascular events was seen in patients with PAD.12
- Antiplatelet therapy. Aspirin 75mg or clopidogrel 75mg.10 The use of clopidogrel to prevent occlusive vascular events in patients who have established PAD has been approved by NICE.13
- Vasoactive drugs. NICE recommends naftidrofuryl for use in patients with PAD and suggests it should be reserved for those whose symptoms have failed to improve with exercise therapy and who do not wish to have angioplasty or surgery. All patients must be reviewed in three to six months and treatment discontinued if there is no symptom improvement.14
- Management of claudication symptoms. Supervised exercise programme, vasoactive medications, referral for interventions when conservative measures have failed and PAD is severely affecting the patient’s lifestyle. Interventions may be angioplasty, stenting or bypass surgery.
- CLI. Patients with diabetes and smokers are at particularly high risk of developing CLI. All patients should be referred urgently.
Quality standard for PAD
NICE Quality Standard 52 covers the diagnosis and management of PAD in adults over the age of 18 years.15 Quality statements are:
- People who have symptoms of, or are at risk of developing, PAD are offered clinical assessment and ABPI measurement
- People with PAD are offered assessment for cardiovascular comorbidities and modifiable risk factors
- People with IC are offered a supervised exercise programme
- People with PAD being considered for revascularisation who need further imaging after a duplex ultrasound are offered magnetic resonance angiography
- People with IC are offered angioplasty only after being advised on the benefits of modifying risk factors, and a supervised exercise programme has not improved their symptoms
Dr Anita Sharma is a GP in Oldham and was the GP member of PAD NICE guideline development group
Information for patients: NHS choices: Peripheral arterial disease.
- Hiatt WR, Hoag S, Hamman RF. Effect of diagnostic criteria on the prevalence of peripheral arterial disease. Circulation 1995; 91: 1472-9
- Criqui MH, Langer RD, Fronek A et al. Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med 1992; 326: 381-6
- Norgren L, Hiatt WR, Dormandy JA et al. Inter-society consensus for the management of peripheral arterial disease. Vasc Surg 2007; 45: S5-67
- Willigendael EM, Teijink JAW, Bartelink ML et al. Smoking and the patency of lower extremity bypass grafts: a meta-analysis. Vasc Surg 2005; 42: 67-74
- Selvin E, Marinopoulos S, Berkenblit G et al. Meta analysis: glycosylated haemoglobin and cardiovascular disease in diabetes mellitus. Ann Intern Med 2004; 141: 421-31
- Murabito JM, D’Agostino RB, Silbershatz H et al. Intermittent claudication. A risk profile from the Framingham Heart Study. Circulation 1997; 96: 44-9
- Alberts M, Bhatt D, Mas J et al. Three-year follow-up and event rates in the REduction of Atherothrombosis for Continued Health Registry. Eur Heart J 2009; 30(19): 2318-26
- Trans-Atlantic Inter-Society Consensus (TASC) Document. J Vasc Surg 2000; 31: S5-35
- Henke P. Contemporary management of acute limb ischaemia: factors associated with amputation and in-hospital mortality. Semin Vasc Surg 2009; 22: 34-40
- Peach G, Griffin M, Jones K et al BMJ 2012; 345: e5208
- NICE. Peripheral arterial disease: diagnosis and management. CG147. London, NICE, August 2012
- Heart Protection Study Collaborative Group. MCR/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002; 360: 7-22
- NICE. Clopidogrel and modified-release dipyridamole for the prevention of occlusive vascular events. TA210. London, NICE, December 2010
- NICE. Cilostazol, naftidrofuryl oxalate, pentoxifylline and inositol nicotinate for the treatment of intermittent claudication in people with peripheral arterial disease. TA223. London, NICE, May 2011
- NICE. Peripheral arterial disease. QS52. London, NICE, January 2014