Summary
Peripheral arterial disease (PAD) is characterized by narrowing and, in final stages, occlusion of the peripheral arteries due to atherosclerotic plaques. Smoking is the most important risk factor for developing PAD. PAD is often a silent disease, but patients may present with features of arterial insufficiency (intermittent claudication, reduced temperature and pulse rate in affected limb, skin discoloration, and trophic changes). On occasion, critical limb ischemia is the only presenting complaint. Segmental blood pressures and pulse volume recordings, particularly the ankle-brachial index (ABI), may support the diagnosis. Further imaging may confirm and assess the location and severity of arterial stenosis or occlusion. Treatment focuses on smoking cessation, graduated exercise, avoiding extremely cold temperatures, and modifying other cardiovascular risk factors. If conservative treatment fails, interventional and surgical management is recommended for low-risk patients with potential long-term success.
Epidemiology
-
Prevalence: 8.5 million in the US
- Prevalence increases with age, starting from the age of 40
- US incidence rates are highest among African Americans, followed by Hispanics, who are at a slightly higher risk than non-hispanic whites.
- Peak incidence: 60–80 years of age
- Sex: ♂ = ♀
References:[1][2]
Epidemiological data refers to the US, unless otherwise specified.
Etiology
- Insufficient tissue perfusion due to atherosclerosis in the aorta and peripheral arteries
- Often coexists with coronary artery disease (CAD), stroke, atrial fibrillation, and renal disease
- See risk factors for atherosclerosis
PAD usually coexists with coronary artery disease. Smoking is the most important risk factor for PAD!
References:[3]
Classification
Fontaine Classification of PAD | |
---|---|
Stage I |
|
Stage II |
|
Stage III | |
Stage IV |
References:[4]
Clinical features
Characteristic features | Description |
---|---|
Silent disease |
|
Intermittent claudication (10–35% of patients) |
|
Absent or diminished pulses | |
Trophic changes |
|
Rest pain |
|
Critical limb ischemia |
A bruit, suggestive of arterial stenosis, may be heard in > 60–70% of cases with PAD!
References:[5][6][7][8]
Diagnostics
Ankle-brachial index (ABI)
- First-line diagnostic test (high specificity and sensitivity) [9]
- Defined as the ratio of systolic ankle blood pressure (BP) to systolic brachial BP
- The ABI is calculated for each leg by dividing the higher systolic pressure of either the dorsalis pedis or posterior tibialis of the respective leg by the higher blood pressure of either the right or left arm
- Normally, ankle BP and brachial BP are equal (ABI = 1), or ankle BP is only slightly higher because of gravity (ABI > 1)
- Differences in systolic BP indicate different pathologies:
- > 1.3 = medial sclerosis with incompressible vascular wall (generally calcified vessels)
- 1.0–1.30 = normal value
- 0.91–0.99 = borderline
- 0.40– 0.90 = mild to moderate PAD → claudication
- < 0.40 = severe PAD → resting pain, gangrene (critical limb ischemia)
- Exercise testing may be required if patients have a normal resting ABI [10]
Imaging
While vascular imaging is not necessarily required for diagnosis, it is useful to determine the site and severity of arterial stenosis or occlusion (especially preoperatively and postoperatively)
- Color-coded duplex ultrasonography
- Digital subtraction angiography (DSA): gold standard
- CT angiography
- MR angiography
- Oscillography
ABI measurements in diabetic or older patients may be inaccurate because of Monckeberg sclerosis!
References:[11][12][13]
Differential diagnoses
Differential diagnosis of claudication | ||||
---|---|---|---|---|
Patient characteristics | Clinical features | |||
Causes of arterial occlusion | Vasculitides | Takayasu arteritis |
|
|
Obliterative endarteritis |
|
| ||
(Lower-extremity) fibromuscular dysplasia |
|
| ||
Popliteal aneurysm |
|
| ||
Arterial embolism |
|
| ||
Popliteal entrapment syndrome |
| |||
Cystic adventitial disease |
|
| ||
Mimics of arterial occlusion | Deep vein thrombosis |
| ||
Spinal stenosis |
|
| ||
Diabetic neuropathy |
|
|
The differential diagnoses listed here are not exhaustive.
Treatment
Conservative [13]
- Smoking cessation!
- Supervised graded exercise therapy
- Foot care (especially in diabetic patients)
- Avoid cold temperatures
Medical therapy
-
Modify cardiovascular risk factors: see therapy of atherosclerotic disease
-
Antiplatelet therapy reduces morbidity and mortality
- Aspirin: irreversible cyclooxygenase inhibition → decreased thromboxane A2 synthesis → decreased platelet aggregation
-
ADP receptor inhibitors
- Clopidogrel: inhibition of the P2Y12 ADP receptor → decreased platelet activation and platelet-fibrin crosslinking
- Ticagrelor; : reversible inhibition of the P2Y12 ADP receptor (otherwise identical downstream effects as clopidogrel)
- Lipid-lowering agent (usually statins)
- Antihypertensive treatment
- Hyperglycemia control
-
Antiplatelet therapy reduces morbidity and mortality
-
PDE inhibitors
-
Cilostazol (the single most effective medication)
- It is indicated in patients with lifestyle-limiting intermittent claudication; only after 3 months of supervised graded exercise therapy.
- It is administered as a therapeutic trial for 3–6 months.
- If no or minimal improvement occurs, consider advanced vascular imaging (see “Imaging” above).
- Mechanisms
- Phosphodiesterase 3 (PDE3) inhibition → increased cAMP → increased activity of protein kinase A → reduced platelet aggregation
- Myosin light chain kinase inhibiton → vascular smooth muscle relaxation → arterial vasodilation
-
Cilostazol (the single most effective medication)
Revascularization[15]
-
Indications [11]
- Critical limb ischemia
- Failure of conservative and pharmacologic treatment
- Inability to perform normal work or activities because of claudication
- No limitations to exercise by other disease (e.g., chronic heart failure) if claudication is improved
- Anatomy of the lesion allows low-risk and long-term success of intervention
- Minimally invasive interventional radiology: percutaneous transluminal angioplasty (PTA) with or without stenting
-
Surgical procedures
- Operative vascular reconstruction (bypass surgery): an autologous vein (e.g., great saphenous vein) is used to bypass the stenosis
- Endarterectomy
Amputation
- Last resort in the event of gangrene
References:[6][7][11][13][15][16]
Complications
-
Arterial ulcer
- Definition: skin defect due to impaired blood flow to the lower extremities
- Etiology: most often seen in peripheral arterial disease
-
Clinical features
- Punched-out ulcer with well-defined borders [17]
- Usually involves the foot, particularly pressure points (e.g., lateral malleolus, tips of the toes)
- Often severe pain [18]
- Differential diagnosis: venous ulcer
- Infection of ulcers; sepsis
- Acute limb ischemia
- Complications of endovascular intervention: see “Complications at the site of vascular access”
- Surgical complications: bleeding, infection of vascular prosthesis, relapse
We list the most important complications. The selection is not exhaustive.
Prognosis
- Intermittent claudication → good prognosis
- Rest pain and/or ischemic ulcers → poor prognosis
- Increased cardiovascular mortality → high risk for secondary MI or stroke
A low ABI in PAD is also predictive of an increased risk of all-cause and cardiovascular mortality! [5]
Prevention
Related One-Minute Telegram
- One-Minute Telegram 6-2020-3/3: Statins underprescribed in patients with PAD
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