Peripheral Arterial Disease: Understanding Risk Factors, Symptoms, and Modern Diagnostic Approaches

Peripheral arterial disease (PAD) represents a significant global health challenge, affecting over 200 million people worldwide and serving as a powerful marker of systemic atherosclerotic burden. This common circulatory condition occurs when narrowed arteries reduce blood flow to the limbs, most commonly the legs, resulting in symptoms ranging from mild discomfort to severe pain and tissue loss. Despite its prevalence and serious implications for both limb viability and cardiovascular mortality, PAD remains underdiagnosed and undertreated in clinical practice. This comprehensive guide explores the epidemiology, pathophysiology, risk factors, clinical presentation, and contemporary diagnostic approaches for peripheral arterial disease, providing evidence-based insights for healthcare professionals and patients navigating this complex condition.

Epidemiology and Global Burden

Prevalence and Distribution

PAD affects diverse populations worldwide:

• Overall prevalence:
• 3-10% of the general population
• 15-20% in adults over age 70
• Higher rates in specific risk groups
• Substantial geographic variations

• Increasing global burden with aging populations

• Gender differences:

• Historically considered male-predominant
• Recent data shows similar prevalence in women
• Different symptom presentation in women
• Later diagnosis in female patients

• Potentially worse outcomes in women

• Ethnic variations:

• Higher rates in Black populations
• Increased prevalence in Hispanic individuals
• Variable rates in Asian populations
• Socioeconomic factors as contributors
• Genetic susceptibility differences

Impact and Consequences

PAD carries significant health and economic burdens:

• Mortality implications:
• 2-3 fold increased cardiovascular mortality
• 5-year mortality rate of 10-15%
• Comparable risk to coronary artery disease
• Mortality increases with disease severity

• Often underappreciated prognostic significance

• Morbidity burden:

• Reduced functional capacity
• Impaired quality of life
• Progressive mobility limitations
• Risk of critical limb ischemia

• Amputation risk in advanced disease

• Economic impact:

• Substantial healthcare costs
• Reduced workforce participation
• Disability-related expenditures
• Caregiver burden
• Rehabilitation requirements

Pathophysiology and Disease Progression

Atherosclerotic Process

Understanding the underlying mechanisms:

• Arterial wall changes:
• Endothelial dysfunction
• Lipid accumulation
• Inflammatory cell infiltration
• Smooth muscle cell proliferation

• Extracellular matrix remodeling

• Plaque development:

• Progressive luminal narrowing
• Arterial wall stiffening
• Reduced vasodilatory capacity
• Compromised collateral formation

• Potential for plaque rupture and thrombosis

• Affected vascular beds:

• Aortoiliac segment
• Femoropopliteal region
• Infrapopliteal arteries
• Multisegment involvement common
• Patterns influence symptomatology

Disease Progression

Natural history without intervention:

• Typical timeline:
• Often decades of subclinical disease
• Gradual symptom development
• Variable progression rates
• Periods of stability possible

• Acute deterioration with thrombotic events

• Progression factors:

• Continued smoking
• Uncontrolled diabetes
• Hypertension severity
• Dyslipidemia management

• Physical activity levels

• Collateral development:

• Compensatory mechanism
• Variable efficiency between individuals
• Enhanced by regular exercise
• Limited in certain conditions (diabetes)
• Critical for maintaining tissue viability

Risk Factors and Prevention

Traditional Risk Factors

Well-established contributors to PAD:

• Tobacco use:
• Strongest modifiable risk factor
• Dose-dependent relationship
• Continued use accelerates progression
• Cessation slows disease advancement

• Benefits begin within months of quitting

• Diabetes mellitus:

• 2-4 fold increased risk
• Earlier disease onset
• More distal arterial involvement
• Accelerated progression

• Worse outcomes including amputation

• Hypertension:

• Contributes to endothelial dysfunction
• Accelerates atherosclerosis
• Compounds hemodynamic compromise
• Often inadequately controlled

• Target organ damage synergy

• Dyslipidemia:

• Elevated LDL cholesterol
• Low HDL cholesterol
• Hypertriglyceridemia
• Lipoprotein(a) emerging role

• Benefit from aggressive management

• Advanced age:

• Progressive risk increase
• Cumulative exposure to risk factors
• Vascular aging processes
• Reduced compensatory capacity
• Comorbidity interactions

Emerging Risk Factors

Newer considerations in risk assessment:

• 炎症指標:
• C-reactive protein
• 白介素
• 腫瘤壞死因子-α
• Fibrinogen

• 髓過氧化物酶

• Metabolic factors:

• Insulin resistance
• Metabolic syndrome
• Obesity (particularly central)
• Non-alcoholic fatty liver disease

• 慢性腎病

• Genetic considerations:

• Family history significance
• Specific genetic polymorphisms
• 表觀遺傳學修改
• Pharmacogenomic implications
• Ethnic susceptibility variations

Preventive Strategies

Approaches to reduce PAD risk:

• Lifestyle modifications:
• Smoking cessation (most important)
• Regular physical activity
• Mediterranean or DASH diet
• Weight management

• Stress reduction

• Medical management:

• Blood pressure control
• Lipid management
• Glycemic control
• Antiplatelet therapy when indicated

• Multifactorial risk intervention

• Screening approaches:

• Risk-based screening strategies
• Ankle-brachial index in high-risk groups
• Integration with cardiovascular risk assessment
• Opportunistic screening during routine care
• 提高公眾意識活動

Clinical Presentation and Symptoms

Symptom Spectrum

Variable manifestations across patients:

• Asymptomatic disease:
• 20-50% of PAD patients
• Detected through screening
• Often significant disease despite absence of symptoms
• Associated with functional impairment

• Same cardiovascular risk as symptomatic PAD

• Intermittent claudication:

• Classic symptom: reproducible exercise-induced discomfort
• Resolves with rest (typically within 10 minutes)
• Location reflects arterial lesion level:
  • Buttock/hip: aortoiliac disease
  • Thigh: common femoral disease
  • Calf: superficial femoral/popliteal disease
  • Foot: infrapopliteal disease
• Stable in 70-80% of patients

• Progresses to critical limb ischemia in 5-10%

• Atypical leg symptoms:

• Particularly common in women and elderly
• Exercise-induced discomfort not meeting classic criteria
• Variable relationship to exertion
• Confounded by comorbidities (arthritis, neuropathy)

• Often misattributed to aging

• Critical limb ischemia:

• Rest pain (typically worse at night, improved with dependency)
• Tissue loss (ulceration or gangrene)
• Severe, persistent pain
• Significant impact on quality of life
• High risk for amputation and mortality

Physical Examination Findings

Key elements of clinical assessment:

• Vascular examination:
• Diminished or absent pulses
• Bruits over stenotic arteries
• Pallor on elevation
• Dependent rubor

• Prolonged capillary refill

• Skin and tissue changes:

• Temperature differences
• Hair loss
• Shiny, atrophic skin
• Thickened nails

• Ulcerations (typically distal or over pressure points)

• Advanced disease findings:

• Muscle atrophy
• Pallor on elevation
• Gangrene
• Tissue necrosis
• Infection signs in ulcerated areas

Functional Impact

Effects on daily living and quality of life:

• Mobility limitations:
• Reduced walking distance
• Avoidance of activities
• Loss of independence
• Social isolation

• Occupational impairment

• Quality of life effects:

• Physical functioning decline
• Psychological impact
• Sleep disturbance with rest pain
• Depression and anxiety
• Fear of amputation

Diagnostic Approaches

Non-Invasive Vascular Testing

First-line diagnostic modalities:

• Ankle-Brachial Index (ABI):
• Gold standard initial test
• Ratio of ankle to brachial systolic pressure
• Interpretation:

  • 0.90: Normal

  • 0.71-0.90: Mild PAD
  • 0.41-0.70: Moderate PAD
  • ≤0.40: Severe PAD

  • 1.30: Non-compressible vessels

• Simple, inexpensive, office-based
• Prognostic value beyond diagnosis

• Limitations with calcified vessels

• Segmental Pressure Measurements:

• Pressures at multiple levels
• Localizes disease segments
• Quantifies hemodynamic significance
• Guides intervention planning

• Useful for monitoring progression

• Pulse Volume Recordings:

• Air plethysmography technique
• Valuable with non-compressible vessels
• Qualitative assessment of perfusion
• Useful for serial monitoring

• Complements pressure measurements

• Exercise Testing:

• Treadmill or active pedal plantar flexion
• Unmasks borderline disease
• Differentiates vascular from non-vascular causes
• Quantifies functional limitation

• Post-exercise ABI enhances sensitivity

• Transcutaneous Oxygen Pressure:

• Measures tissue oxygenation
• Helpful for wound healing assessment
• Guides amputation level decisions
• Identifies microcirculatory dysfunction
• Predicts revascularization outcomes

Advanced Imaging Techniques

Detailed anatomical and functional assessment:

• Duplex Ultrasonography:
• Non-invasive, radiation-free
• Provides anatomical and physiological data
• Characterizes plaque morphology
• Quantifies stenosis severity

• Useful for surveillance after intervention

• Computed Tomographic Angiography (CTA):

• Excellent spatial resolution
• Rapid acquisition
• Visualizes vessel wall and surrounding structures
• Limitations with calcification

• Contrast and radiation considerations

• Magnetic Resonance Angiography (MRA):

• No ionizing radiation
• Excellent soft tissue contrast
• Options for non-contrast techniques
• Functional flow assessment

• Limitations with stents and claustrophobia

• Digital Subtraction Angiography (DSA):

• Historical gold standard
• Now primarily reserved for intervention
• Highest spatial resolution
• Pressure gradient measurement capability
• Invasive with contrast and radiation exposure

Emerging Diagnostic Technologies

Newer approaches with potential advantages:

• Near-Infrared Spectroscopy:
• Non-invasive tissue perfusion assessment
• Exercise-enhanced protocols
• Microcirculatory evaluation
• Research applications expanding to clinical use

• Potential for wearable monitoring

• Hyperspectral Imaging:

• Maps tissue oxygenation
• Identifies compromised perfusion
• Wound healing potential assessment
• Non-contact technology

• Emerging role in critical limb ischemia

• Perfusion Angiography:

• Quantitative assessment of tissue perfusion
• Performed during conventional angiography
• Guides intervention endpoints
• Predicts wound healing potential

• Emerging standardization of techniques

• Intravascular Ultrasound and OCT:

• Detailed plaque characterization
• Guides intervention strategy
• Assesses calcium burden
• Evaluates stent deployment
• Identifies dissection and other complications

Diagnostic Algorithm and Clinical Approach

Initial Evaluation

Systematic assessment pathway:

• History elements:
• 症狀特徵
• Risk factor assessment
• Functional limitation quantification
• Comorbidity evaluation

• Prior vascular interventions

• Physical examination focus:

• Comprehensive pulse examination
• Skin and tissue assessment
• Neurological evaluation
• Wound characteristics if present

• Signs of venous disease (differential diagnosis)

• Initial testing:

• Ankle-brachial index
• Basic laboratory assessment
• Electrocardiogram
• Consider exercise ABI if symptoms atypical
• Risk factor evaluation (lipids, glucose)

Risk Stratification

Determining disease severity and prognosis:

• Symptom classification:
• Rutherford classification (0-6)
• Fontaine staging (I-IV)
• WIfI classification for tissue loss
• Functional impairment assessment

• 對生活品質的影響

• Hemodynamic severity:

• ABI values
• Pressure gradients
• Exercise response
• Tissue perfusion measures

• Collateralization assessment

• Anatomical considerations:

• TASC II classification
• Lesion location and length
• Vessel calcification
• Outflow status
• Prior intervention sites

Advanced Assessment

Tailored to clinical scenario:

• Claudication evaluation:
• Functional testing (treadmill, 6-minute walk)
• 生活品質評估
• Anatomical mapping if intervention considered
• Exclusion of non-vascular causes

• Cardiovascular risk assessment

• Critical limb ischemia approach:

• Urgent hemodynamic assessment
• Tissue perfusion evaluation
• Infection assessment
• Anatomical mapping for revascularization planning
• Multidisciplinary team involvement

醫療免責聲明

重要通知: This information is provided for educational purposes only and does not constitute medical advice. Peripheral arterial disease is a serious medical condition that requires proper evaluation and management by qualified healthcare professionals. The diagnostic approaches discussed should only be implemented under appropriate medical supervision. Individual diagnostic and treatment decisions should be based on patient-specific factors, current clinical guidelines, and physician judgment. If you are experiencing symptoms such as leg pain with walking, non-healing wounds, or color changes in your feet, please consult with a healthcare professional for proper evaluation and treatment recommendations. This article is not a substitute for professional medical advice, diagnosis, or treatment.

總結

Peripheral arterial disease represents a significant global health challenge with implications extending far beyond the affected limbs. As a powerful marker of systemic atherosclerosis, PAD signals increased risk for cardiovascular events and mortality, making early diagnosis and comprehensive management essential. The diagnostic approach to PAD has evolved significantly, with a range of non-invasive and advanced imaging modalities allowing for precise characterization of disease severity and anatomical distribution. A systematic diagnostic algorithm incorporating clinical assessment, physiological testing, and selective use of advanced imaging provides the foundation for appropriate management decisions. As diagnostic technologies continue to advance, the focus remains on earlier detection, better risk stratification, and more personalized approaches to this common but often underdiagnosed condition.