History and exam

Key diagnostic factors

common

presence of risk factors

Key risk factors include smoking, diabetes, hyperlipidaemia, and a history of coronary artery disease or cerebrovascular disease.

asymptomatic

Most patients with peripheral arterial disease are asymptomatic and diagnosis is based on risk factors.

intermittent claudication

It is important to assess patients with detailed questions on walking impairment, claudication symptoms, ischaemic rest pain, or presence of non-healing wound/foot ulcer. Classic claudication symptoms occur in a minority of patients.

thigh or buttock pain with walking that is relieved with rest

Intermittent claudication can also occur in the larger muscle groups of the upper leg. This is indicative of narrowing of the deep femoral artery or aorto-iliac level disease.

diminished or absent pulse

Key component of physical examination includes assessment of pulses in all extremities. Palpation of pulses at the brachial, radial, ulnar, femoral, popliteal, dorsalis pedis, and posterior tibial artery is essential. Also, auscultation of carotid, femoral, and abdominal vessels is essential to assess for bruit.

uncommon

sudden onset of severe leg pain accompanied by numbness, weakness, pale, and cold leg

The classic 6 signs of acute limb ischaemia are: pain, paralysis, paraesthesias, pulselessness, poikilothermia, and pallor.

Other diagnostic factors

common

erectile dysfunction

May be an early sign of peripheral arterial disease. Erectile dysfunction may be a symptom of aorto-iliac atherosclerotic disease.[50]

uncommon

leg pain at rest

May be a sign of chronic limb-threatening ischaemia.[2] The pain is severe and will be associated with chronic ischaemic signs on their physical examination. The pain is worse when the patient is supine and may be better when the leg is dependent.

gangrene

Necrosis that may involve one or more toes or other parts of the foot (i.e., heel). This is a sign of chronic limb-threatening ischaemia.[2]

non-healing wound/ulcer

A non-healing wound/ulcer in the lower extremities below the level of the knee may be a sign of chronic limb-threatening ischaemia, particularly if it persists despite appropriate wound care.[2]

muscle atrophy

Muscle atrophy of one lower extremity (reduced circumference compared with the contralateral extremity) may be suggestive of peripheral arterial disease.[2]

dependent rubor

Sign of critical limb ischaemia.

pallor when the leg is elevated

Sign of acute limb ischaemia.[2]

loss of hair over the dorsum of the foot

Suggestive of peripheral arterial disease.[2]

nail bed changes

Suggestive of peripheral arterial disease.[2]

shiny/scaly skin

Suggestive of peripheral arterial disease.[2] Due to loss of subcutaneous tissue.

pale extremity

Sign of acute limb ischaemia.[2]

nerve loss

Sign of acute limb ischaemia.[2]

Risk factors

strong

smoking

Because the most common aetiology of peripheral arterial disease (PAD) is atherosclerosis, the risk factors for PAD are similar to those of coronary artery disease (CAD).[2]​ However, smoking is 2-3 times more likely to cause PAD than CAD.​[3] Smoking is the most powerful predictor and is independently associated with the development of PAD; an almost 4-fold increased risk of PAD due to smoking has been reported (odds ratio per year 3.83; 95% CI 2.49 to 5.91). Additionally, a dose-dependent association between smoking and the severity of PAD has been supported.[12] Both active and passive cigarette smoking impair flow-mediated endothelium-dependent peripheral arterial vasodilation (arterial stiffness). Smoking cessation is therefore essential to prevent disease progression, as well as to decrease clinical deterioration (i.e., walking distance) and amputation rates.[13][14][15][16]

diabetes

Diabetes is a risk factor for development and progression of peripheral arterial disease (PAD) and they are common comorbidities. In large epidemiology studies, diabetes has been shown to increase the risk of PAD by 2- to 4-fold.[2] Diabetes increases the risk of intermittent claudication by 3- to 9-fold. The risk is proportional to the severity and duration of diabetes. Patients with both PAD and diabetes are 7-15 times more likely to undergo limb amputation. The UK Prospective Diabetes Study Group showed that each 1% increase in glycosylated haemoglobin levels is associated with a 28% increased risk of incident PAD and with a 28% increased risk of death, independent of other variables, such as blood pressure, serum cholesterol, age, or smoking status. Thus, aggressive control of hyperglycaemia in diabetes mellitus is essential to prevent disease progression and reduce cardiovascular risk.[17][18][19]

hypertension

Hypertension is a common comorbidity; it is identified in 35% to 55% of patients with peripheral arterial disease (PAD) at diagnosis.[20]​ It is a key risk factor for PAD, with odds ratios for hypertension ranging from 1.5 to 2.2.[2][21]​ In the Framingham Heart Study, PAD was increased by the severity of hypertension and the risk of intermittent claudication overall was increased 2- to 4-fold.[22] An even higher population risk attributable to hypertension of 41% was reported in the Health Professionals Follow-up Study.​[23]

Risk factor modifications should include control of blood pressure.[24][25] The Heart Outcomes Prevention Evaluation (HOPE) study found that treatment with the angiotensin-converting enzyme inhibitor ramipril was associated with a reduced risk of vascular death, myocardial infarction, and stroke in a broad range of patients who were at high risk for cardiovascular events, including those with PAD.[26]​​

The Appropriate Blood Pressure Control in Diabetes study demonstrated the superiority of intensive over moderate blood pressure control.[27] Patients with diabetes receiving intensive antihypertensive treatment had significantly fewer cardiovascular events compared with those patients on moderate blood pressure-lowering treatment.

hyperlipidaemia

Elevated total cholesterol, low-density lipoprotein (LDL), triglycerides, and lipoprotein(a) have been associated with increased risk of peripheral arterial disease (PAD).[2] Decreased levels of high-density lipoprotein have also been associated with increased risk. The risk of PAD increased by 5% to 10% for each 10 mg/dL rise in total cholesterol. Therefore, aggressive pharmacological management of lipid abnormalities in patients with PAD (e.g., with statins) is crucial.[28]

Lowering LDL cholesterol (LDL-C) levels not only reduces the atherosclerosis burden in these patients (thus decreasing disease progression), but also reduces cardiovascular event, morbidity, and mortality rates.[2]​​[29]

High-dose statin therapy has been shown to be more effective at preventing PAD than moderate-dose therapy.[30]

age >40 years

Prevalence increases from 0.9% in 40- to 49-year-olds to 14.5% in people over 70 years of age.[31]

history of coronary artery disease/cerebrovascular disease

The same risk factors that predispose to coronary disease and stroke increase the risk of peripheral arterial disease (PAD). A personal or family history of these conditions increases the risk of developing PAD.[2]

low levels of exercise

Individuals who do not take regular physical exercise are at increased risk of developing peripheral arterial disease. Regular exercise also produces favourable alterations in cardiovascular risk factor profile.[32]

chronic kidney disease (CKD)

Patients with CKD have an increased risk of developing peripheral arterial disease (PAD) and the risk increases with severity of renal impairment.[2][33]​​ Up to 25% of patients with CKD have PAD, and this increases to 45% in those with end-stage renal disease.[2]

weak

elevated C-reactive protein (CRP)

Physicians' Health Study found an increased risk of developing peripheral arterial disease in men with elevated baseline levels of CRP.[34]​​

hyperhomocysteinaemia

An elevated homocysteine level is associated with an increased risk of peripheral arterial disease (PAD).[35][36]​​ Elevated levels of homocysteine increase the risk of progression of PAD. There is, however, no evidence to support treatment of hyperhomocysteinaemia in PAD.[35]

vasculitis/inflammatory conditions

The presence of a vasculitis such as Buerger's disease or Takayasu's arteritis, particularly in combination with smoking, can increase the risk of developing peripheral vascular disease.[37]

arterial fibrodysplasia

This can affect any artery, but often involves the femoral, iliac, and popliteal arteries and can contribute to peripheral vascular disease, particularly in younger patients.[38]

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