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Peripheral Vascular Disease (PVD) - Comprehensive Review

Definition & Overview

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Etiology and Pathophysiology

Primary Cause

• Atherosclerosis (>90% of cases): lipid accumulation, foam cell formation, plaque development, fibrous cap, eventual stenosis/occlusion

Secondary and Non-Atherosclerotic Causes

Risk Factors for PAD

• Smoking (strongest modifiable risk factor; severity correlates with pack-years)
• Diabetes mellitus
• Hypertension
• Hyperlipidemia / elevated LDL
• Age >50 years
• Male sex (though women with PAD often present atypically)
• Chronic kidney disease / ESRD
• Elevated homocysteine (~1 in 3 PAD patients)
• Elevated C-reactive protein (inflammation drives atherosclerosis)
• Positive family history (heritability ~20%)

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Spectrum of PVD - Major Categories

PERIPHERAL VASCULAR DISEASE
├── Arterial Disease (PAD)
│   ├── Chronic Stable (Claudication)
│   ├── Chronic Limb-Threatening Ischemia (CLTI)
│   └── Acute Limb Ischemia (ALI)
├── Venous Disease
│   ├── Chronic Venous Insufficiency
│   ├── Deep Vein Thrombosis
│   └── Varicose Veins
└── Lymphatic Disease
    └── Lymphedema

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Classification Systems

1. Fontaine Classification (1954) - Chronic PAD

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2. Rutherford Classification (1986, revised) - Chronic Limb Ischemia

• Current Surgical Therapy 14e, p. 1142

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3. Rutherford Classification - Acute Limb Ischemia (ALI)

• Bailey & Love's Surgery 28e, p. 1033

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4. WIfI Classification (SVS, 2014) - Chronic Limb-Threatening Ischemia

• Wound (W): 0=no ulcer/gangrene, 1=small ulcer, 2=deep ulcer/toe gangrene, 3=extensive ulcer/gangrene
• Ischemia (I): 0=ABI ≥0.80, 1=ABI 0.70-0.79, 2=ABI 0.40-0.59, 3=ABI ≤0.39
• foot Infection (fI): 0=none, 1=mild (≤2 cm cellulitis), 2=moderate (deep structures involved), 3=severe (SIRS present)

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5. TASC II Classification - Anatomic Distribution (Aortoiliac & Femoropopliteal)

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Clinical Presentation

Symptomatic Spectrum

• ABI <0.9 but no symptoms (most common presentation - ~50% of cases)
• Still carries full cardiovascular risk

• Reproducible cramping, aching, or fatigue in muscle groups during exercise, relieved within 2-5 minutes of rest
• Calf claudication = femoropopliteal disease
• Buttock/thigh claudication = aortoiliac disease (Leriche syndrome: bilateral buttock claudication + impotence)
• Must be distinguished from pseudo-claudication (neurogenic - spinal stenosis): pain on standing, relieved by bending forward, not purely by rest

• Rest pain (typically worse at night, relieved by hanging leg down)
• Ischemic ulcers (punched-out, painful, on tips of toes/pressure areas, no granulation tissue)
• Gangrene

• Pain (severe, sudden onset)
• Pallor
• Pulselessness
• Parasthesia (numbness)
• Paralysis (late, ominous sign)
• Perishing cold (poikilothermia)

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Investigations

Non-Invasive Vascular Studies

• Used when ABI is falsely elevated (non-compressible arteries in DM/CKD)
• Normal TBI: 0.70-0.80
• Minimum toe pressure for wound healing: 30 mmHg (40 mmHg in diabetics)
• Diagnostic of PAD: TBI <0.70

• Pressure cuffs at thigh, calf, ankle
• Gradient >20 mmHg between adjacent segments = significant stenosis
• Localizes level of disease

• Plethysmographic waveform analysis at each segment
• Normal = triphasic; PAD = biphasic, then monophasic, then flat

• Standard protocol: 3.2 km/hr at 12% incline for 5 minutes
• Post-exercise ABI drop >20% = significant PAD
• Useful when resting ABI is normal but symptoms are classic

• Combines B-mode imaging + Doppler velocity
• Sensitivity/specificity >90% for ≥50% stenosis
• Peak systolic velocity ratio >2.0 = >50% stenosis
• First-line for surveillance of bypass grafts and stents

Imaging

• Requires iodinated IV contrast + ionizing radiation
• Excellent visualization of stents and calcified plaque
• ~1/4 radiation of DSA
• Faster and easier than MRA

• No ionizing radiation; gadolinium contrast (avoid in GFR <60 - risk of nephrogenic systemic fibrosis)
• Cannot be used with ferromagnetic implants (pacemakers, ICDs)
• Tends to overestimate stenosis at vessel ostia (turbulent flow artifact)
• Better soft tissue contrast than CTA

• Gold standard for diagnosis and pre-procedural planning
• Allows concurrent intervention (angioplasty/stenting)
• Complications: contrast allergy 0.1%, access-site bleeding, contrast-induced nephropathy
• Reserved for pre-intervention planning or when non-invasive imaging is inconclusive

PAD Diagnosis Algorithm

Laboratory Tests

• CBC (anemia, polycythemia)
• Lipid panel (LDL-C target <70 mg/dL in established PAD)
• HbA1c and fasting glucose (diabetes screen/monitoring)
• BMP/CMP (renal function - contrast planning)
• Coagulation studies (PT, PTT, INR)
• Homocysteine (elevated in ~33% of PAD patients)
• CRP / ESR (inflammation markers)
• Hypercoagulable workup (if young patient, atypical presentation, or bilateral disease without typical risk factors)

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2024 ACC/AHA Guidelines - Key Updates

Major New Recommendations

• ABI screening recommended for patients >65 years, or >50 years with DM + smoking history
• Women with PAD often present atypically - sex-aware screening emphasized
• New: "Risk Amplifiers" table including CKD, ESRD, history of prior MACE

• Aspirin 75-325 mg/day OR clopidogrel 75 mg/day for symptomatic PAD
• NEW - Rivaroxaban 2.5 mg BID + Aspirin 100 mg/day: Class I recommendation for patients with symptomatic PAD, based on the COMPASS trial (27% reduction in MACE + MALE)
• Single antiplatelet still preferred over DAPT for claudication alone

• 3 sessions/week × 12 weeks of supervised exercise
• Effect size rivals or exceeds stenting for claudication
• Must be prescribed before or alongside revascularization for claudication

• High-intensity statin for all PAD patients regardless of LDL
• LDL-C goal <70 mg/dL for CLTI; consider PCSK9 inhibitors if not achieved

• WIfI score mandated before revascularization decisions
• Multidisciplinary team-based care (vascular surgeon, podiatrist, wound care, endocrinologist)
• Revascularization should aim to restore "straight-line pulsatile flow" to the foot

• Structured foot inspection at every visit for all PAD patients
• Footwear assessment and patient education

• Align largely with ACC/AHA
• Emphasize rivaroxaban + aspirin for LEAD (lower extremity artery disease) with high ischemic/low bleeding risk
• Recommend CTA or MRA as first-line imaging (before DSA)

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Treatment

A. Medical (Guideline-Directed Therapy)

1. Smoking Cessation (Class I - strongest recommendation)

• Single most effective intervention to slow PAD progression
• Bupropion and varenicline improve abstinence rates
• Reduces mortality, limb loss, and graft failure

2. Antiplatelet Agents

• Aspirin 75-325 mg/day
• Clopidogrel 75 mg/day (equal or superior to aspirin; preferred in aspirin intolerance)
• Rivaroxaban 2.5 mg BID + Aspirin 100 mg (2024 ACC/AHA Class I for symptomatic PAD without high bleeding risk - COMPASS/VOYAGER PAD evidence)
• Ticagrelor: no proven advantage over clopidogrel in EUCLID trial

3. Statins

• High-intensity (atorvastatin 40-80 mg or rosuvastatin 20-40 mg)
• LDL goal <70 mg/dL; add ezetimibe or PCSK9 inhibitor if needed
• Additional benefit: increases claudication walking distance (2 independent trials)

4. Antihypertensive Therapy

• Target BP <130/80 mmHg
• ACE inhibitors preferred (ramipril: 25% reduction in cardiac events in PAD patients)
• Beta-blockers: previously feared to worsen claudication - disproven in RCT; safe to use

5. Diabetes Management

• HbA1c goal <7.0% (SVS guidelines)
• SGLT2 inhibitors and GLP-1 agonists have additional cardiovascular benefit

6. Pharmacotherapy for Claudication

7. Homocysteine

• Folic acid + B12 lowers homocysteine levels, but no RCT evidence for reduction in cardiovascular events

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B. Supervised Exercise Therapy

• 3 sessions/week for 12 weeks minimum (ideally 26 weeks)
• Walking until claudication onset → rest → resume
• Improves walking distance, functional capacity, and quality of life
• Class I, Level A evidence in 2024 ACC/AHA guidelines
• Effect rivals endovascular revascularization for claudication (CLEVER trial: exercise = stenting for quality of life at 18 months)

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C. Endovascular Revascularization

Indications

• Claudication: failed ≥3 months of medical + exercise therapy AND lifestyle-limiting symptoms
• CLTI: urgent; preferred when anatomy suitable
• ALI: emergent (onset <14 days preferred over open surgery)

Endovascular Procedures

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D. Open Surgical Revascularization

Indications

• TASC C/D lesions (complex, long segment)
• Failed endovascular procedures
• ALI >14 days (surgical thrombectomy)
• High surgical risk anatomy unsuitable for endovascular

Bypass Surgery Options

Amputation

• Class III ALI (irreversible ischemia)
• Unreconstructable CLTI with uncontrolled infection/sepsis
• Levels: digital → transmetatarsal → below-knee (BKA) → above-knee (AKA)
• Early rehabilitation with prosthesis is the goal

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E. Treatment by Clinical Syndrome - Summary

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Complications and Prognosis

• Cardiovascular mortality: Leading cause of death in PAD (MI, stroke)
• Limb loss: 1-year major amputation rate in CLTI ~20-25%
• Reperfusion injury: After revascularization in ALI - compartment syndrome, rhabdomyolysis, hyperkalemia, renal failure
• Graft failure: 30-40% of femoro-popliteal bypasses occlude within 5 years
• Restenosis: Major limitation of endovascular therapy (10-40% within 1 year for SFA stenting)

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Recent Evidence (2024-2025)

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Key Pearls for Clinical Practice

1. ABI is the cornerstone - measure in any patient with leg symptoms, DM over 50, or age over 65
2. ABI >1.40 in diabetics/ESRD → get TBI instead (non-compressible arteries give false normal reading)
3. Exercise therapy before stenting for claudication - equal or better outcomes in multiple trials
4. Rivaroxaban 2.5 mg BID + aspirin is now Class I for symptomatic PAD in the 2024 guidelines
5. Rutherford Grade III ALI (sensory + motor loss + no Doppler signals) = go straight to amputation - no angiography
6. WIfI score before every CLTI revascularization decision
7. Cilostazol is contraindicated in heart failure (any class) - important prescribing restriction
8. Women with PAD often present without classic claudication - lower threshold for ABI testing
9. Buerger's disease (thromboangiitis obliterans): young male smokers, distal involvement, no atherosclerosis risk factors - complete smoking cessation is the only proven therapy

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