Peripheral arterial disease (PAD) is the internationally recognised term to describe chronic lower limbs atherosclerotic disease, leading to a reduction of lower limb arterial blood supply. This is part of a systemic atherosclerotic process which not only has local impact on the loss of mobility and functional decline, but is a major marker for widespread cardiovascular disease. The severity of PAD is associated with an increased risk of cardiovascular death, of all-cause mortality and is the third leading cause of atherosclerotic cardiovascular morbidity.

This is a worldwide disease which has increased throughout all income level countries in recent years. This, coupled with our ageing population, has lead to a large burden of disease and has become a public health challenge. To this end there is a growing international move (which includes the Irish Heart Foundation, European Angiology Days and the WHO with the first WHO PAD Awareness Day in March 2014) to promote awareness, in an attempt to achieve earlier diagnosis and improve treatment of the disease.

Epidemiological studies report total disease prevalence of PAD in the 3-33% range, where objective testing was performed. The prevalence increases with age to one in 10 for people over 70 years. The prevalence rates have increased globally by 23.5%, in the 10 years to 2010, to an estimated 202 million cases. 

Presentation

The spectrum of PAD ranges from the sub-clinical, the asymptomatic patient, the non-healing ulcer, rest pain through to the amputee. The location and the type of symptoms is dependant in the level of disease, severity of the occlusion and the physical activity of the patient. The classic intermittent claudication symptom of pain on exertion (in a major muscle group, of the lower limb) which is relieved by rest is only reported in 10% of patients with PAD documented on objective testing. The exercise limitation symptom may be described as pain, fatigue, numbness or tiredness, typically in buttock, thigh, calf or foot. The presence or absence of symptoms has no impact on outcome and indeed may be masked by the reduced mobility of the patient. The natural history of the disease is progressive stenosis to occlusion, with 25% of patients progressing to critical limb ischemia. Symptoms can commonly  be mistaken for musculoskeletal or neurological conditions, which contributes to the underdiagnosis of lower limb PAD.

Diagnosis 

The diagnosis is made by objective non-invasive measurement of upper and lower limb blood pressure and is expressed as ankle brachial index (ABI) or ankle brachial pressure index (ABPI).

Measurement of ankle brachial indices

In simple terms the ankle brachial index is a comparison of brachial systolic pressure to ankle systolic pressure and is simple to perform in any surgery or clinic room. The only equipment that is required is a hand-held Doppler and a sphygmomanometer. Guidelines on the measurement and interpretation of ABIs were published by the American Heart Association in 2012. Although there are several methods for measuring blood pressure, they recommend measurement using a Doppler probe. Systolic pressures are measured from both brachial arteries and from the posterior tibial and anterior tibial arteries bilaterally. The guidelines also emphasise the importance of appropriate cuff size (cuff width should be 40% of limb circumference). A simple protocol is recommended for resting ABIs and this includes:

• Patient resting for 5-10 minutes
• Supine position
• Non-smoking for two hours
• All pressures to be measured by Doppler
• The first reading should always be repeated and an average taken.

To calculate the ABI, the ankle systolic pressure is divided by the higher of the brachial systolic pressures.

Recommendations for interpretation are:

• ABI < 0.90 is the threshold for confirming the presence of PAD
• When the ABI is > 0.90 but there is a clinical suspicion of PAD then post-exercise ABIs should be measured
• Individuals with an ABI < 0.90 or > 1.4 should be considered at increased risk of CV events independently of the presence of symptoms of PAD.

It is recommended that the measurement of ABIs should be part of the standard curriculum for medical and nursing students, and all health professionals who perform ABI should have didactic as well as experiential training. 

Patients who should have ABIs measured fall into three main groups:

• Suspicion of PAD
• Assessment of cardiovascular risk
• Management of lower extremity ulceration.

The measurement of ABIs is a simple, non-invasive and repeatable test which provides invaluable information in the early identification of PAD.

Risk factors

The major cause of lower limb PAD is atherosclerosis and the risk factors include cigarette smoking, diabetes, dyslipidaemia, hypertension and homocysteinaemia.

Treatment

The primary treatment goal in the PAD patient is to impede the progression of the disease and to prevent lower limb amputation, with a secondary goal to decrease future cardiovascular events. Treatment is primarily medical until the disease progresses to the limb-threatening stage where revascularisation is indicated.  

Medical management of PAD

In 2013, updated recommendations were published by the American College of Cardiology/American Heart Foundation task force on the management of patients with PAD, the most robust being Class I (representing an intervention that is proven to be beneficial and effective), with level of evidence A (derived from multiple randomised trials or meta-analysis), to the lowest of Class III, level C.

Medical management comprises management of cardiovascular risk factors with particular attention to smoking cessation and supervised exercise programmes.  

Smoking

The amount and duration of cigarette consumption directly correlates with the development and progression of PAD increasing the risk by a factor of eight to 10. Tobacco cessation not only improves PAD prognosis and progression but also improves the pain-free walking distance. It has been shown that the use of multiple rather than single intervention modalities significantly increases the smoking cessation rates and can result in a cessation rate of up to one-third on first attempt. Interventions should including multiple sessions, particularly face to face with both physicians and counsellors and in the absence of contraindications should include pharmacological therapies such as varenicline, bupropion and nicotine replacement therapy (Class I, level A evidence). 

The addition of varenicline has shown a modest increase over nicotine replacement patches alone, but a higher success rate than bupropion and a two to three increase over placebo. However, the concern remains over depressive mood, agitation and suicidal thoughts.  

In Ireland there is currently a HSE QUIT online support system which has reported increased usage since its inception.  

Tobacco cessation at age 30 avoids all risk associated with tobacco consumption, while stopping at 60 can add three years of healthy life.  

Exercise therapy and pharmacology 

Unstructured advice to exercise has been shown to have little effectiveness in the treatment of PAD in comparison to supervised exercise programmes (Class I level A evidence). The aim of the exercise is to achieve a high level of claudication pain during the exercise sessions. The sessions should comprise cycles of exercise and rest comprising of a 30 minute session three times a week, initially increasing to a 60 minute session. Duration of the exercise programme should be at least 12 weeks and this shows up to a 66% increase in the pain-free walking distance; however benefit is lost if exercise after a three-month period is not continued.  

Pharmacological intervention with cilostazol, a phosphodiesterase 111 inhibitor with vasodilator and antiplatelet activity, 100 mg BD PO, is the only agent shown to increase both maximum and pain-free walking distance (Class I, level A) and as such should be considered in the patient with lifestyle-limiting claudication, but is contraindicated in the presence of congestive cardiac failure. 

Phentoxifylline 400mg TDS may be considered as a second-line, but effect is marginal (Class IIb level A).

Other medical therapies

Nutritional supplements with a large L-arginine have been shown to have a small impact (18%) on the pain-free walking distance (Class IIb , level B) but this is significantly lower than that achieved by exercise alone (66%).  

Similarly, propionyl-L-carnitine and ginkgo biloba are not well established (Class 11b, level B).

Vasodilator prostaglandins, vitamin E and chelation are not effective to improve walking distance (Class 111).

Blood pressure

Blood pressure control has no direct affect on the symptoms or pain-free walking distance in PAD patients.  However, a target blood pressure control of less than 140/90mmHg with further reduction in the diabetics to 130/80mmHg is recommended to reduce the risk of MI, stroke and cardiovascular death (Class I, level A).

Lipid lowering

Statins are recommended to achieve reduction in total cholesterol to less than 4.5mg/l and LDL to less than 2.6mg/l. (Class IIa, level B)

In the presence of multiple risk factors low HDL, normal LDL and increased triglycerides the addition of fibric acid derivate is recommended (Class IIa, level B).  

Conclusion

While PAD is common, with increasing prevalence, it is under diagnosed, with only 10% of patients presenting with classical symptoms. 

PAD not only reduces functional capacity and quality of life, but can also progress to amputation and is associated with increase mortality rate. Earlier diagnosis and medical management, with emphasis on exercise and smoking cessation, can arrest the progression of the disease and add years of healthy living.  

References

1. Fowkes FG et al. Comparison of global estimates of prevalence and risk factors for peripheral disease in 2000 and 2010: a systematic review and analysis. Lancet  2013 Oct 19;382(9901):1329-40
2. Doll R, Hill AB. The mortality of doctors in relation to their smoking habits: a preliminary report. BMJ 1954; 26;328 (7455): 1529-33 
3. Lancaster T et al. Effectiveness of interventions to help people stop smoking: findings from the Cochrane Library. BMJ 2000; 5;321(7257):355-8
4. Chen YF et al. Effectiveness and cost-effectiveness of computer and other electronic aids for smoking cessation: a systematic review and network meta-analysis. Health Technol Assess. 2012;16(38):1-205
5. Stoyioglou A, Jaff MR. Medical treatment of peripheral arterial disease: a comprehensive review. J Vasc Interv Radiol. 2004 Nov;15(11):1197-207
6. Norgren L et al. Inter-society consensus for the management of peripheral arterial disease. Int Angiol 2007 Jun;26(2):81-157
7. Anderson JL et al. Management of patients with peripheral artery disease (compilation of 2005 and 2011 ACCF/AHA guideline recommendations): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013 Apr 2;127(13):1425-43