Lower extremity arterial occlusive disease is a chronic condition caused by atherosclerosis affecting the arteries of the lower limbs, leading to arterial stenosis or occlusion and resulting in ischemic symptoms in the limbs. It represents the manifestation of systemic atherosclerotic disease in the lower extremities.
Etiology and Pathogenesis
This disease is considered equivalent in risk to coronary artery disease, as the risk factors for coronary atherosclerosis are also commonly associated with this condition. The pathogenesis is similar to that described in atherosclerosis. Smoking increases the incidence by 2-5 times, while diabetes increases it by 2-4 times.
Pathophysiology
The primary pathophysiological mechanism causing ischemic symptoms in the limbs is impaired regulation of blood supply to the affected extremity. This includes thickening of arterial plaques, insufficient collateral circulation, poor compensatory vasodilation, reduced nitric oxide production, diminished responsiveness to vasodilators, and increased circulating vasoconstrictors such as thromboxane, angiotensin II, and endothelin. Additionally, abnormalities in blood rheology contribute to dysregulation of blood supply and microthrombosis formation.
Clinical Manifestations
The disease involves the aorta and iliac arteries in 30% of cases, the femoral and popliteal arteries in 80-90%, and the tibial and peroneal arteries in 40-50%.
Symptoms
The typical symptoms include intermittent claudication and rest pain. Intermittent claudication is characterized by localized pain, tightness, numbness, or weakness triggered by physical activity and relieved by rest. The location of pain often correlates with the affected artery. Pain in the buttocks, hips, or thighs with intermittent claudication often suggests partial obstruction of the aorta and iliac arteries. The most common presentation is calf pain during intermittent claudication, typically caused by femoral or popliteal artery stenosis. Pain in the ankles or toes during intermittent claudication is frequently associated with tibial or peroneal artery disease. Progression of the disease leading to arterial occlusion may result in rest pain. Commonly used clinical staging systems include Fontaine staging and Rutherford classification.
Table 1 Clinical staging of lower extremity arterial occlusive disease
Signs
Diminished or absent arterial pulses distal to the stenosis are with systolic murmurs audible over the stenotic site.
The affected limb may feel colder, with thin, shiny, pale skin, sparse hair, and thickened toenails. Severe cases may present with edema, gangrene, or ulcers.
Positional changes in the limb may indicate arterial stenosis and poor collateral formation. A time of >10 seconds for skin color to return to red after lowering the limb from an elevated position, or >15 seconds for superficial vein filling, suggests arterial stenosis and inadequate collateral circulation.
Auxiliary Examinations
Ankle-Brachial Index (ABI)
ABI is the simplest and most commonly used clinical test, calculated as the ratio of ankle systolic pressure to brachial systolic pressure. The normal range is 1.0-1.4. A value of 0.91-0.99 is considered "borderline," while <0.90 indicates the presence of peripheral arterial disease (PAD). An ABI >1.40 is often associated with vascular calcification. The sensitivity of ABI for diagnosing PAD is 95%, but in cases of severe stenosis with well-developed collateral circulation, false-negative results may occur.
Segmental Blood Pressure Measurement
A pressure gradient between segments suggests the presence of arterial stenosis.
Exercise Treadmill Test
This test evaluates the blood supply to the limb by assessing the workload and duration until ischemic symptoms appear.
Doppler Ultrasound
As arterial stenosis progresses, Doppler blood flow velocity curves become flattened. Combined with imaging results, this method provides more reliable diagnostic information.
Magnetic Resonance Angiography (MRA) and CT Angiography (CTA)
These imaging modalities are valuable for confirming the diagnosis.
Arteriography
This provides direct evidence for surgical or percutaneous interventional treatment planning.
Diagnosis and Differential Diagnosis
The diagnosis is generally straightforward when patients present with typical symptoms of intermittent claudication or rest pain, combined with physical signs such as asymmetry, weakening, or absence of arterial pulses in the limbs, along with an analysis of risk factors and auxiliary examination results. However, it is noteworthy that less than 20% of confirmed patients exhibit the classic symptom of intermittent claudication.
This condition should be differentiated from Takayasu arteritis involving the iliac arteries and thromboangiitis obliterans (also known as Buerger's disease). Takayasu arteritis is more common in young females and is characterized by systemic symptoms during the active phase, such as fever, elevated erythrocyte sedimentation rate, and abnormal immune markers. The lesions are often multifocal, frequently involving the renal arteries and causing renovascular hypertension. Buerger's disease primarily affects young male heavy smokers, involving small- and medium-sized arteries throughout the body, including the upper limbs. It is often associated with recurrent superficial phlebitis and Raynaud's phenomenon. Ischemic ulcers with severe pain should be distinguished from those caused by neuropathy or venous ulcers due to varicose veins. Additionally, claudication should be differentiated from pseudoclaudication caused by conditions such as spinal stenosis, arthritis, or compartment syndrome.
Treatment
Medical Therapy
Smoking cessation, control of hypertension, diabetes, and dyslipidemia are essential. Proper wound care, including cleaning, moisturizing, and preventing trauma, is recommended. For patients with rest pain, elevating the head of the bed may enhance lower limb blood flow and reduce pain.
Exercise and Rehabilitation Therapy
Regular aerobic exercise can improve maximum walking distance. Exercise should be performed under professional guidance, with each session lasting 30-45 minutes at least three times per week for a minimum of 12 weeks. Recommended exercises include walking, ankle flexion, and knee flexion. Routine exercise therapy is not advised for patients in Fontaine stage IV.
Antiplatelet and Anticoagulant Therapy
Antiplatelet agents such as aspirin and clopidogrel can reduce the risk of myocardial infarction, stroke, and vascular-related death in patients with lower extremity arterial occlusive disease. Cilostazol, which has both antiplatelet and vasodilatory properties, is considered a first-line treatment for intermittent claudication. Conventional anticoagulants, such as warfarin, do not reduce cardiovascular events and may increase the risk of major bleeding.
Prostaglandin Drugs
Prostaglandin-based medications can dilate blood vessels, alleviating symptoms such as intermittent claudication and rest pain.
Pain Management
Pain relief can follow a stepwise approach, starting with nonsteroidal anti-inflammatory drugs (NSAIDs). If ineffective, opioid analgesics may be considered.
Anti-Infection Therapy
For patients with ischemic ulcers or gangrene complicated by infection, broad-spectrum antibiotics should be administered based on pathogen identification, in adequate dosages and for an appropriate duration.
Revascularization
Revascularization may be considered for patients who continue to experience rest pain, tissue necrosis, or significant disability despite aggressive medical therapy. Endovascular interventions include intra-arterial thrombolysis, thrombectomy, balloon angioplasty, and stent placement. These procedures are associated with low perioperative complication rates and are often the first choice. For cases where the guidewire cannot pass through the lesion, surgical options such as endarterectomy or bypass grafting may be selected.
Amputation
Amputation is necessary for patients with extensive necrosis or infectious gangrene accompanied by rest pain, inability to walk, and unsuitability for revascularization.
Prognosis
The prognosis of this disease is closely related to coexisting coronary artery disease and cerebrovascular disease. The 5-year survival rate for patients with intermittent claudication is approximately 70%, and the 10-year survival rate is about 50%, with most deaths attributed to coronary artery disease and cerebrovascular events. Patients with diabetes and those who smoke have a poorer prognosis, with approximately 5% requiring amputation.