What are the typical presentation, differential diagnosis (ddx), investigations (invx), management (mx), and complications of Peripheral Arterial Disease (PAD)?

Peripheral Arterial Disease: Clinical Presentation, Diagnosis, Management, and Complications

Peripheral Arterial Disease (PAD) presents with four distinct clinical subsets: asymptomatic PAD, chronic symptomatic PAD, chronic limb-threatening ischemia (CLTI), and acute limb ischemia (ALI), each requiring specific diagnostic approaches and management strategies based on disease severity and presentation. 1

Typical Presentation (Signs and Symptoms)

Clinical Subsets of PAD

1. Asymptomatic PAD

   • No reported leg symptoms but may have functional impairment
   • Patients often self-limit activity to avoid symptoms
   • Affects 20-59% of patients with objectively proven PAD 1
   • Associated with increased risk of cardiovascular events and mortality 1

2. Chronic Symptomatic PAD

   • Most common clinically evident subset
   • Includes claudication and other ischemia-related exertional leg symptoms
   • Typical claudication: pain, aching, cramping, or fatigue in buttocks, thigh, calf, or foot
   • Symptoms occur consistently during walking, not at rest
   • Usually relieved within 10 minutes of rest 1
   • Other symptom descriptors: tingling, numbness, burning, throbbing, or shooting 1

3. Chronic Limb-Threatening Ischemia (CLTI)

   • Severe clinical subset affecting 11-20% of PAD patients 1
   • Manifests as ischemic rest pain, nonhealing wounds/ulcers, or gangrene
   • Symptoms present for >2 weeks 1
   • Rest pain often affects forefoot, worsens with limb elevation, relieved by dependency
   • Responsible for most PAD-related amputations 1

4. Acute Limb Ischemia (ALI)

   • Severe clinical subset with sudden onset of symptoms (<14 days)
   • Requires immediate revascularization to prevent irreversible tissue damage 2
   • Can lead to irreversible tissue damage within 4-6 hours 2

Physical Examination Findings

• Diminished or absent pulses (femoral, popliteal, dorsalis pedis, posterior tibial)
• Vascular bruits (especially femoral)
• Elevation pallor and dependent rubor
• Asymmetric hair growth and calf muscle atrophy
• Poikilothermia (cooler temperature in affected limb)
• Thickened, brittle, or discolored toenails
• Nonhealing wounds or ulcers (in advanced cases)
• Gangrene (black, necrotic tissue in distal areas) 2

Differential Diagnosis (DDx)

Several conditions can mimic PAD symptoms:

Condition	Location	Characteristics	Effect of Exercise	Effect of Rest	Other Features
Hip arthritis	Lateral hip, thigh	Aching discomfort	After variable exercise	Not quickly relieved	Improved when not weight-bearing
Foot/ankle arthritis	Ankle, foot, arch	Aching pain	After variable exercise	Not quickly relieved	May improve when not weight-bearing
Nerve root compression	Radiates down leg	Sharp lancinating pain	Variable with sitting, standing, walking	Often present at rest	Improved by position change
Spinal stenosis	Bilateral buttocks, posterior leg	Pain and weakness	May mimic claudication	Variable relief	Relief by lumbar spine flexion
Popliteal cyst	Behind knee, down calf	Swelling, tenderness	With exercise	Present at rest	Not intermittent
Venous claudication	Entire leg, worse in calf	Tight, bursting pain	After walking	Subsides slowly	Relief with leg elevation
Chronic compartment syndrome	Calf muscles	Tight, bursting pain	After strenuous exercise	Subsides very slowly	Typically in muscular athletes

1

Investigations (InVx)

Initial Diagnostic Testing

1. Ankle-Brachial Index (ABI)

   • First-line diagnostic test for PAD 2
   • Interpretation:
     • ≤0.90: Confirms PAD diagnosis
     • 0.91-0.99: Borderline, requires additional testing
     • 1.00-1.40: Normal

     • 1.40: Noncompressible, requires alternative testing 2

2. Exercise ABI

   • Useful when resting ABI is normal but clinical suspicion is high
   • Post-exercise ABI decrease >20% is diagnostic for PAD 2

3. Toe-Brachial Index (TBI)

   • Alternative when ABI >1.30 (noncompressible vessels)
   • Abnormal if <0.70 2
   • Particularly useful in patients with diabetes or renal failure 2

4. Pulse Volume Recordings (PVR)

   • Useful when ABI is nondiagnostic or vessels are noncompressible 1

Advanced Imaging

1. Duplex Ultrasound

   • First-line imaging test
   • Assesses location and extent of occlusion, collateral circulation 2

2. CT Angiography (CTA)

   • Provides detailed anatomical information
   • Useful for planning revascularization 2

3. MR Angiography (MRA)

   • Alternative to CTA, especially in patients with renal insufficiency 2

4. Invasive Angiography

   • Reserved for concurrent intervention
   • Gold standard for anatomical assessment 2

Management (Mx)

Risk Factor Modification

1. Smoking Cessation

   • Physician advice, nicotine replacement therapy, bupropion 3
   • Critical for improving symptoms and reducing cardiovascular events 3

2. Exercise Therapy

   • Supervised exercise programs
   • Improves walking distance and quality of life 3, 4

3. Lipid Management

   • High-intensity statin therapy for all PAD patients 2, 4

4. Blood Pressure Control

   • Target <140/90 mmHg
   • ACE inhibitors preferred 2, 3

5. Diabetes Management

   • Target HbA1c <7%
   • Consider GLP-1 receptor agonists and SGLT-2 inhibitors 2, 4

Pharmacological Therapy

1. Antiplatelet Therapy

   • Single antiplatelet (clopidogrel preferred over aspirin) 4
   • Reduces risk of cardiovascular events 3

2. Cilostazol

   • For patients with lifestyle-limiting claudication
   • Improves pain-free and peak walking distances 3, 5
   • Contraindicated in heart failure 6

Revascularization

Indicated for:

• Lifestyle-limiting claudication despite optimal medical therapy
• Chronic limb-threatening ischemia
• Acute limb ischemia 2

Options include:

1. Endovascular Therapy

   • Angioplasty, stenting
   • Less invasive, preferred for focal lesions 2

2. Surgical Revascularization

   • Bypass surgery
   • For extensive disease or failed endovascular therapy 2

3. Hybrid Procedures

   • Combination of endovascular and surgical approaches 2

Complications

1. Cardiovascular Events

   • Increased risk of myocardial infarction, stroke, and cardiovascular death 3
   • PAD is a marker for systemic atherosclerosis 1

2. Limb-Related Complications

   • Progressive claudication
   • Development of CLTI
   • Tissue loss and gangrene
   • Amputation (major and minor) 1

3. Functional Decline

   • Reduced walking capacity
   • Decreased quality of life
   • Loss of independence 1, 3

4. Mortality

   • 25-35% 1-year mortality rate in patients with CLTI 1
   • Significantly higher mortality compared to age-matched controls 3

Key Pitfalls to Avoid

1. Attributing leg symptoms solely to arthritis or neuropathy without considering PAD 2
2. Relying on pulse palpation alone for diagnosis 2
3. Failing to screen high-risk patients 2
4. Delaying treatment for acute limb ischemia 2
5. Not addressing cardiovascular risk factors in asymptomatic PAD patients 1

PAD management requires a comprehensive approach addressing both limb symptoms and cardiovascular risk, with treatment strategies tailored to the clinical subset and disease severity.