Peripheral Artery Disease: Pathophysiology, Risk Factors, Clinical Features, Diagnosis, Management and Prevention

Peripheral Artery Disease (PAD): Pathophysiology, Diagnosis and Management

~Introduction

Peripheral Artery Disease (PAD) is a common circulatory disorder characterized by narrowing or blockage of arteries supplying the limbs, most often the legs. This condition primarily results from atherosclerosis, where fatty deposits (plaques) build up on arterial walls, restricting blood flow. PAD is a major cause of morbidity worldwide, affecting millions of people, especially older adults and those with diabetes or smoking history. It is also a marker of systemic atherosclerosis and is associated with increased risk of heart attack and stroke.

PAD can be asymptomatic or present with symptoms ranging from intermittent claudication to critical limb ischemia. Early diagnosis and appropriate management are crucial to prevent complications such as gangrene and limb amputation.

~Epidemiology

Peripheral artery disease affects more than 200 million people globally, with higher prevalence in older adults. The risk rises significantly after age 50 and is more common in men, though postmenopausal women are increasingly affected. The global burden is increasing due to aging populations and rising rates of diabetes, hypertension, and obesity.

In India and other developing nations, PAD is underdiagnosed and undertreated, often due to lack of awareness and limited access to vascular care.

~Anatomy and Pathophysiology

The peripheral arterial system supplies oxygenated blood from the aorta to the limbs and other peripheral tissues. In PAD, atherosclerosis is the predominant cause of obstruction.

Mechanism

1. Endothelial injury occurs due to risk factors such as smoking, hypertension, or hyperlipidemia.

2. Lipid infiltration and inflammation lead to the formation of atherosclerotic plaques.

3. Plaque progression narrows the arterial lumen, reducing blood flow.

4. Plaque rupture or thrombosis can cause acute limb ischemia.

Reduced perfusion to tissues causes ischemic pain, impaired healing, and in advanced stages, necrosis and gangrene.

~Risk Factors

Several modifiable and non-modifiable factors contribute to PAD development.

1. Modifiable Risk Factors

• Smoking: The most important risk factor; smokers have up to four times higher risk.

• Diabetes Mellitus: Causes endothelial dysfunction and accelerates atherosclerosis.

• Hypertension: Damages arterial walls and promotes plaque formation.

• Hyperlipidemia: Elevated LDL and low HDL levels accelerate plaque buildup.

• Obesity and Sedentary Lifestyle: Reduce peripheral circulation.

• Chronic Kidney Disease: Associated with vascular calcification.

2. Non-Modifiable Risk Factors

• Age: Incidence increases significantly after 50 years.

• Gender: Slight male predominance in early age; women are more affected in older age.

• Genetics: Family history of atherosclerosis or cardiovascular disease increases risk.

~Classification

Peripheral artery disease is classified based on severity and location.

1. Anatomic Classification

• Aortoiliac disease: Involves the arteries supplying the pelvis and thighs.

• Femoropopliteal disease: Involves arteries of the thigh and knee.

• Infrapopliteal disease: Affects arteries below the knee (tibial and peroneal).

2. Functional Classification

Fontaine Stages

Stage	Description
I	Asymptomatic
II	Intermittent claudication
III	Rest pain (ischemic pain at night)
IV	Ulcers or gangrene (critical limb ischemia)

Rutherford Classification

A more detailed scale (0–6) describing symptoms from asymptomatic (0) to severe tissue loss (6).

~Clinical Features

The clinical presentation of PAD depends on the degree of arterial obstruction and collateral circulation.

1. Intermittent Claudication

• The hallmark symptom of PAD.

• Described as cramping, aching, or fatigue in the calves, thighs, or buttocks after walking a specific distance, relieved by rest.

• Caused by muscle ischemia during exertion.

2. Rest Pain

• Occurs in advanced stages when blood flow is inadequate even at rest.

• Typically affects the toes and feet, worsens at night, and improves when the leg is dangled off the bed.

3. Non-Healing Ulcers and Gangrene

• Result from chronic ischemia and tissue necrosis.

• Often develop on toes, heels, or pressure points.

4. Other Signs

• Cool, pale skin on the affected limb.

• Weak or absent peripheral pulses.

• Shiny skin, loss of hair, brittle toenails.

• Delayed capillary refill and prolonged wound healing.

~Complications

Untreated or advanced PAD can lead to severe consequences:

• Critical Limb Ischemia (CLI): Persistent rest pain, ulcers, or gangrene.

• Acute Limb Ischemia: Sudden occlusion leading to limb-threatening emergency.

• Amputation: From irreversible gangrene.

• Cardiovascular Events: PAD patients have a 6-fold increased risk of heart attack and stroke.

• Infection: Due to ulceration and poor tissue perfusion.

~Diagnosis

A thorough clinical evaluation supported by non-invasive and imaging studies is essential for diagnosis.

1. History and Physical Examination

• Detailed assessment of risk factors and symptoms.

• Pulse examination: Femoral, popliteal, dorsalis pedis, and posterior tibial arteries.

• Skin inspection for color, temperature, ulcers, and trophic changes.

2. Ankle-Brachial Index (ABI)

• Primary screening test for PAD.

• ABI = (Ankle systolic pressure) / (Brachial systolic pressure).

• Normal: 1.0–1.4

• Borderline: 0.91–0.99

• Abnormal (PAD): ≤0.90

• Severe ischemia: <0.40

ABI is quick, non-invasive, and reliable for early detection.

3. Doppler Ultrasound

• Assesses blood flow and identifies the site and extent of stenosis.

4. Imaging Studies

a) Computed Tomography Angiography (CTA)

• Provides detailed visualization of arterial anatomy and occlusions.

• Useful for surgical or endovascular planning.

b) Magnetic Resonance Angiography (MRA)

• Non-invasive and free of ionizing radiation.

• Offers 3D imaging of arteries.

c) Digital Subtraction Angiography (DSA)

• Gold standard for diagnosis and intervention.

• Allows simultaneous therapeutic procedures (angioplasty or stenting).

5. Laboratory Tests

• Lipid profile, blood glucose, renal function, and inflammatory markers.

• Useful to assess cardiovascular risk and comorbidities.

~Differential Diagnosis

PAD must be differentiated from other conditions causing leg pain or ischemia:

• Neurogenic claudication (spinal stenosis)

• Chronic venous insufficiency

• Deep vein thrombosis

• Buerger’s disease (thromboangiitis obliterans)

• Musculoskeletal disorders (arthritis, myalgia)

~Management

Management of PAD focuses on symptom relief, functional improvement, and prevention of cardiovascular events. Treatment can be medical, interventional, or surgical depending on the stage and severity.

1. Lifestyle Modification

The cornerstone of PAD management:

• Smoking cessation – the single most effective intervention.

• Regular exercise: Supervised walking programs improve collateral circulation and walking distance.

• Healthy diet: Low-fat, high-fiber diet to control cholesterol.

• Weight management: To reduce cardiovascular load.

2. Pharmacological Therapy

a) Antiplatelet Therapy

• Aspirin (75–325 mg/day) or Clopidogrel (75 mg/day) reduces risk of cardiovascular events.

• Dual therapy may be considered in high-risk patients.

b) Statins

• Lower LDL cholesterol and stabilize atherosclerotic plaques.

• Recommended for all PAD patients regardless of baseline cholesterol.

c) Antihypertensive Agents

• ACE inhibitors or ARBs are preferred for their cardiovascular protective effects.

• Beta-blockers are safe in PAD contrary to earlier beliefs.

d) Glycemic Control

• Strict control in diabetic patients slows progression of PAD.

e) Cilostazol

• A phosphodiesterase III inhibitor that improves walking distance and reduces claudication symptoms.

• Contraindicated in patients with heart failure.

f) Pentoxifylline

• Improves erythrocyte flexibility and blood flow; less effective than cilostazol.

3. Interventional Management

When medical therapy fails or ischemia becomes critical, revascularization is indicated.

a) Endovascular Therapy

• Percutaneous transluminal angioplasty (PTA): Balloon dilation of the stenosed artery.

• Stenting: Placement of a stent to maintain patency.

• Atherectomy: Removal of atherosclerotic plaque using specialized devices.

Advantages: Minimally invasive, shorter recovery, and high success rates in focal lesions.

b) Surgical Revascularization

Indicated for long-segment occlusions or failed endovascular therapy.

• Bypass grafting: Using autologous vein (saphenous vein) or synthetic grafts.

• Endarterectomy: Removal of plaque from arterial wall.

c) Amputation

Reserved for non-reconstructable disease with irreversible gangrene or infection.

~Management of Critical Limb Ischemia (CLI)

Critical limb ischemia represents the most severe form of PAD with rest pain or tissue loss.
Management includes:

• Immediate pain control and infection management.

• Revascularization (endovascular or surgical) wherever possible.

• Wound care and debridement.

• Hyperbaric oxygen therapy in selected cases.

• Amputation if limb salvage is not feasible.

~Complications of Treatment

• Restenosis or graft occlusion.

• Infection at surgical or catheter sites.

• Embolization or thrombosis during angioplasty.

• Contrast-induced nephropathy after imaging or intervention.

~Prognosis

The long-term prognosis of PAD depends on the stage at diagnosis and adherence to treatment.

• Mild PAD (claudication) can remain stable or improve with lifestyle changes.

• Advanced disease with critical ischemia carries high risk of amputation and mortality.

• PAD patients have up to a 6-fold increased risk of cardiovascular death compared to non-PAD individuals.

Early detection and comprehensive management significantly improve quality of life and survival.

~Prevention

Prevention strategies target modifiable risk factors:

• Regular screening (ABI testing) in high-risk individuals.

• Smoking cessation and public health education.

• Control of diabetes, blood pressure, and lipids.

• Healthy diet and regular exercise.

• Regular foot care in diabetics to prevent ulcers.

~Recent Advances

• Drug-eluting stents and balloons: Reduce restenosis rates after angioplasty.

• Gene and cell therapy: Experimental approaches to stimulate angiogenesis in ischemic limbs.

• Artificial intelligence (AI): Used for automated image analysis and early PAD detection.

• Wearable technologies: Devices that monitor blood flow and walking performance.

~Conclusion

Peripheral Artery Disease is a major manifestation of systemic atherosclerosis and an important cause of disability and mortality. Although often underdiagnosed, it provides an opportunity for early detection of widespread vascular disease. Comprehensive management—combining lifestyle changes, pharmacologic therapy, and revascularization—can significantly improve limb outcomes and survival.

Public awareness, early screening, and multidisciplinary care involving cardiologists, vascular surgeons, and primary physicians are essential to reduce the global burden of PAD.