Peripheral Arterial Disease
Definition/DescriptionPeripheral arterial disease (PAD) is known as a condition where by the blood flow in the limb arteries are obstructed . Commonly, the legs are the . These arteries are obstructed due to plaque deposits that restrict blood flow through the peripheries . Although blood flow may be also restricted by deep vein thrombosis, which may be a blood clot that occurs in the periphery of the limbs . Most patients are asymptomatic, but may experience intermittent claudication (pain on walking). Common symptoms of PAD include pain during walking and rest, skin ulcers,
cramping, aching, clubbing of the finger or toenails, cold skin, blue tinged skin, and slow blood refill . Thus there is a lack of blood flow to remove anaerobic metabolites that cause a pain sensation when built up . Critical limb ischaemia occurs when the blood flow reduction is so severe that it causes pain on rest or loss of tissue (ulceration or gangrene).
Peripheral artery disease affects around 13% of the Western population who are more than 15 years old. In the United Kingdom, an estimated 500-1000 new cases of PAD are diagnosed per million each year. Patients at high risk of PAD are those with cardiac disease, diabetes mellitus, older than 70 years or 50 years old with multiple cardiovascular factors. These factors include smoking, dyslipedmia, dysglycemia, hypertension, family history of atherosclerotic vascular disease. In lower socioeconomic areas, PAD is more frequent as a result of increased incidence of smoking . Some studies report no difference in prevalence between the sexes , however, other studies have found a 3:1 ratio comparing men to women. A few studies have suggested that black non-Hispanics have an increased prevalence of PAD, with a reported 2.39 to 2.83 odd ratio. Although, a study that controlled for atherosclerotic risk factors found a small difference between whites and African Americans; 1.54 and 1.89, respectively. The majority of cases are asymptomatic..
The most common cause of PAD is atherosclerosis, similarly, they share the same risk factors: smoking, diabetes, age, hypertension, and hyperlipidemia. Uncommon vascular symptoms, such as vasculitis, thromboangiitis obliterans, popliteal entrapment syndrome, and fibromuscular dysplasis, account for less than 10% of cases .
Atherosclerosis is a systemic disease. It is the formation of lipid deposits in the tunica media and associated with damage to the endothelial lining .The endothelial cells become swollen with lipids and create a gap between in the linings. Platelets stick to the exposed collagen fibers, forming a localized clot that restricts arterial blood flow, leading to inadequate tissue perfusion. This and other complex interactions can lead to progression from asymptomatic PAD, Intermittent Claudication, Critical Limb Ischemia, Acute Limb Ischemia . It is estimated that up to 60% of patients with PAD will have ischaemic heart disease, and 30% have cerebrovascular disease. Reports suggest that within 5 years of diagnosis, 10-15% of patients suffering from intermittent claudication will die from cardiovascular disease. This highlights the importance of identification and modification of risk factors associated with PAD, heart disease, and stroke.
Cigarette smoking increases the chance of having PAD by seven-fold . Due to a change in the fibrin formation, endothelial cells, blood rheology, and lipoproteins decrease antioxidants in the blood . Specifically, the change in endothelial cells that line the arterial walls is strongly associated with atherosclerosis . As the number of cigarettes smoked each day increase, so does the risk of PAD . A systematic review of 17 studies (n=20,278) reported that half of all PAD can be attributed to smoking and concluded that heavier smokers are more likely to develop PAD than light smokers. Moreover, they suggested that former smokers still have an increased risk when compared with patients who have never smoked.
Diabetes, similarly to smoking causes abnormalities in endothelial cells and their function. The cells are unable to regulate the function and structure of the arterial walls. Diabetes Mellitus leads to a two-to fourfold increase in risk of cardiovascular events . The TASC II guidelines report that those with diabetes have a similar relative risk of developing PAD to those that smoke.  A prospective cohort study found that poor diabetes management was associated with an increased risk of PAD. 
Age - The risk of PAD increases as the population approaches the age of 50. It has been reported that PAD affects 0.9% of 40-49 year olds and increases to 14.5% of 70 year olds and above .Studies also have shown that men are the target population of PAD .
Gender - TASC II guidelines conclude that men are affected at a younger age than women. However, overall there is no clear distinction in risk.
Hypertension - In a study conducted by Lewington et al. illustrated that for each 20-mmHg increase in systolic blood pressure or 10 mmHG in diastolic for people age 40-70 doubled the risk of cardiovascular disease and PAD .
Dyslipidemia - Developing PAD by 10% for every 10-mg/dL rise in total cholesterol.
If PAD is left untreated it does not inevitably lead to amputation. At five years from diagnosis most patients with claudication have stable or improved symptoms. Asymptomatic disease is identified as a marker of sedentary lifestyle rather than less severe disease and outcomes are similar to those with claudication. As much as 25% of symptomatic patients will need some form of intervention, but less than 5% of those will progress to critical limb ischaemia.  The risk of amputation is 1-3.3% and all-cause mortality is 20% within five years from diagnosis of PAD.  The risk of limb amputation is 30% in patients with critical limb ischaemia and five year all-cause mortality is 50%.  Mortality rates for all patients that require leg amputation are twice as high when compared to those without amputation. Patients presenting with diabetes are at a greater risk of amputation or dying when compared to non-diabetic patients with PAD. 
Most patients with PAD are asymptomatic. Claudication is the most reported symptom. It is an aching or burning sensation in the muscles of the leg that it reliably reproduced after a set walking distance and is relieved with rest. It is not exacerbated by position or present at rest. The site of pain can often help in providing an indication to the site of the disease. Occlusion or stenosis of the aorta commonly causes bilateral buttock, thigh, and calf claudication. Occlusion of the common iliac, common femoral, and superficial femoral arteries causes unilateral buttock, thigh, and calf claudication.
For a diagnosis of acute limb ischemia a patient must present with a sudden onset of the Six P's (Pain, Pallor, Pulseless, Parasthesia, Paralysis, 'Perishingly cold, Sudden onset of claudication.
The video below is a good summary of the basics of PAD
A tool used to gain a diagnosis of PAD is Ankle Brachial Pressure Index (ABI), a simple and inexpensive test that measures the ratio between blood pressure in the legs to the blood pressure in the arms. The lower the pressure in the legs illustrates that PAD is present. An ABI of 0.9- 1.0 is normal, 0.70-0.89 is a mild disease, 0.40- 0.69 is a moderate disease, and less than .40 is a severe PAD. When measuring for ABI, make sure the patient is calm and in a rested position . It is also important to assess individuals if they have diabetes, non-healing wounds on their legs and feet, unexplained pain in their peripherals, and check for femoral and popliteal pulses.
Other investigations that are commonly used in the assistance of a diagnosis of PAD are Blood pressure, Electrocardiography, Full blood count, Urea and electrolytes, Random blood glucose or HBA1C, Serum cholesterol, Thrombophillia screen in patients less than 50 years old.
According to NICE:
- non-healing wounds on legs or feet
- unexplained leg pain
- pain on walking that resolves when stopped
- pain in foot at rest made which worsens with elevation
- dry skin
The current NICE clinical guidelines on Cardiovascular disease have identified several key aspects in the management of PAD in the primary care setting. It identifies that all patients should receive the following before a referral is made to secondary care. These include;
- Risk Factor Modification
- Smoking cessation therapy - Patients with PAD that continue to smoke persistently have worse outcomes. A 2016 AHA ( American Heart Association) statement was updated to include that patients with PAD are now strongly advised to avoid second-hand smoke. When compared with former smokers, they have a greater risk of amputation and their chance of surviving 5 years post diagnosis is halved when compared to non-smokers. It is important that patients are made aware of this association with smoking and the benefits of smoking cessation. A combination of behavioural counselling with medication has been shown to increase the proportion of successful attempts at quitting when compared to standard care. Cessation of smoking may help in preventing further declines in symptoms.
- HBA1C control (target value <48 mmol/mol) - Numerous studies have shown that an improvement in glycemic control in patients with diabetes reduces the risk of microvascular complications, but has little effect on the risk of amputation. NICE recommend reaching a target HBA1C level of <48 mmol/mol for all patients with diabetes. 
- Blood pressure control (target value <140/90 mm Hg- for patients <80 years old) - Management of hypertension lowers a patients cardiovascular risk. Ramipril is recommended as first line therapy in guidelines worldwide.
- Clopidogrel (or aspirin) 75 mg lifelong - An RCT of patients with atherosclerotic vascular disease showed that clopidogrel 75 mg was significantly better than aspirin 325 mg for prevention of vascular complications at a mean follow up of 1.9years. When clopidogrel is contraindicated, aspirin is an acceptable alternative. Warfarin is most commonly reserved for patients with limb ischaemia due to arterial emboli.
- Atorvastatin lifelong - A meta- analysis of 12 observational studies reported that statin therapy plays a role in reducing all-cause mortality and the incidence of stroke in those with PAD. NICE guidelines recommend reducing non- HDL cholesterol concentration in patients with PAD by 40%. 
- Symptom control
- Supervised exercise therapy for 3 months - NICE recommends that a supervised exercise programme is offered to all patients where applicable consisting of 2hrs a week for a 3month period.  They report that it is more cost effective than either unsupervised exercise or angioplasty. Despite this, it is estimated that up to 70% of clinical commission groups in the UK fail to provide this service.
One method of treating PAD is to reduce cardiovascular risk factors by quitting smoking, managing diabetes mellitus, treating dyslipidemia and hypertension . Another method is to treat PAD symptoms to improve quality of life through pharmacotherapy, exercise rehabilitation program, revascularization, thrombolysis and surgical procedures .
The least invasive and most appropriate treatment for PAD conducted by Physiotherapists would be by prescribing an exercise program. The recommended parameters of physical exercise are a 6 month program of 30-35 minutes walking sessions at a frequency of 3-5 times a week at near-maximal pain tolerant.
Supervised exercise programs have proved to be have better results that unsupervised exercise programs. An updated Cochrane review 2018 reports that the original version of this review was released in 2006, prescribed exercise therapy consisted mostly of “go home and walk” advice. However the compelling evidence now suggests that "Evidence of moderate and high quality shows that SET (supervised exercise programs) provides an important benefit for treadmill‐measured walking distance (MWD and PFWD) compared with HBET (home based exercise programs) and WA (walking advice) respectively."
Even for clients having invasive therapies exercise is important A 2018 Cochrane review comparing mono invasive therapies (monotherapies) to supervised exercise programs (SET) with invasive therapies, concluded " that exercise is a complication-free treatment, it appears to offer significant improvements in patients walk distances with a combination of both SET and intervention offering a superior walking outcome to monotherapy in those requiring invasive measures."
A 2018 review of the best exercise perscription for PAD summarised their findings thus
- Supervised treadmill exercise improves treadmill walking performance in patients with PAD.
- Supervised treadmill exercise has greater benefit on treadmill walking performance than home-based walking exercise.
- Home-based walking exercise interventions that involve behavioral techniques are effective for functional impairment in people with PAD and improve the 6-min walk distance more than supervised treadmill exercise.
- Upper and lower extremity ergometry improve walking performance in patients with PAD and improve peak oxygen uptake.
- Lower extremity resistance training can improve treadmill walking performance in PAD, but is not as effective as supervised treadmill exercise.
The optimal exercise program for PAD recommended by the American Heart Association states the following
Exercise Prescription for Supervised Exercise Treadmill Training in Patients With Claudication
- Modality Supervised Treadmill Walking
- Intensity 40%–60% maximal workload based on baseline treadmill test or workload that brings on claudication within 3–5 min during a 6-MWT
- Session duration 30–50 min of intermittent exercise; goal is to accumulate at least 30 min of walking exercise
- Claudication intensity Moderate to moderate/severe claudication as tolerated
- Work-to-rest ratio Walking duration should be within 5–10 min to reach moderate to moderately severe claudication followed by rest until pain has dissipated (2–5 min)
- Frequency 3 times per week supervised
- Program duration At least 12 wk
- Progression Every 1–2 wk: increase duration of training session to achieve 50 minAs individuals can walk beyond 10 min without reaching prescribed claudication level, manipulate grade or speed of exercise prescription to keep the walking bouts within 5–10 min
- Maintenance Lifelong maintenance at least 2 times per week
Based on currently available evidence. Exercise prescription should be individualized to each patient as tolerated. 6-MWT indicates 6-minute walk test. 
According to Warren there are several methods one can prevent PAD. Firstly, help change the patient's lifestyle by educating them on the risk factors and the effects PAD. If the patient smokes cigarettes, it is important to address the issue and promote cessation. Those who consume a high fat diet have a higher chance of being diagnosed with PAD, thus one should encourage a reduced fat diet as a strong prevention method. Along with diet, it is important to live an active lifestyle. By being active and working up to the general standards of physical activity per week will allow a decrease in weight along with a decrease in risk of PAD.
Highlights from the 2016 AHA advice regarding PAD management
- Patients with peripheral artery disease (PAD) should be on a program of guideline-directed medical therapy (including antiplatelet drugs that thin blood and statins to lower cholesterol) and should participate in a structured exercise program.
- Restoring blood flow to the legs through vascular procedures is appropriate for many patients with severe symptoms due to PAD.
- Eliminating exposure to all tobacco – including second-hand smoke – is highly recommended for patients with PAD.
Peripheral Vascular Disease, NHS Choices
Peripheral Arterial Disease, Circulation FoundationPeripheral Artery Disease, Mayo Clinic
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