Peripheral Arterial Occlusive Disease

Aka: Peripheral Arterial Occlusive Disease, Peripheral Arterial Disease, Peripheral Artery Disease, Peripheral Vascular Disease, Arterial Insufficiency, Claudication, Vascular Claudication, Aortoilliac Occlusive Disease, Leriche's Syndrome, Iliac Artery Stenosis, Iliofemoral Occlusive Disease, Femoropopliteal Occlusive Disease, Femoropopliteal Stenosis, Femoral Arterial Stenosis, Intermittent Claudication, Arterial Atherosclerosis, Arteriosclerosis, Arterial Occlusive Disease

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II. Background

  1. Claudication derived from latin claudicatio, to limp

III. Epidemiology: Prevalence

  1. Overall
    1. 7-12 million affected in United States
    2. 200 million affected worldwide
  2. Age
    1. Age over 60 years: 3 to 6%
    2. Age over 70 years: 10 to 18%
    3. Age over 85 years: 50%
  3. References
    1. Benjamin (2018) Circulation 137(12): e67-492 [PubMed]

IV. Risk Factors

  1. Precautions
    1. Risks are additive (1.5 fold increase for 1 risk factor, 10 fold increase with 3 or more risk factors)
  2. Age over 60 (Odds Ratio 4.1)
  3. Cerebrovascular Disease (Odds Ratio 3.6)
  4. Coronary Artery Disease (Odds Ratio 3.5)
  5. Diabetes Mellitus (Odds Ratio 2.5)
  6. Hyperlipidemia (Odds Ratio 1.9)
  7. Tobacco Abuse (risk persists >5 years after cessation)
    1. Cigarette smoking 20 per day: 2.11 Relative Risk
    2. Cigarette smoking 11-20 per day: 1.75 Relative Risk
    3. In one study, 80% of PAD cases were in current or former smokers
    4. Meijer (1998) Arterioscler Thromb Vasc Biol 18(20: 185-92 [PubMed]
  8. Black race
  9. Systolic Hypertension
  10. Hyperhomocysteinemia
  11. Increased Body Mass Index (Obesity)
  12. C-Reactive Protein increased
  13. Chronic Kidney Disease with GFR rate <60 ml/min/1.73m2
  14. Eraso (2014) Eur J Prev Cardiol 21(6): 704-11 [PubMed]

V. Associated Conditions

  1. Coronary Artery Disease (Myocardial Infarction)
    1. Major adverse cardiac events (MI, CVA, CV-related death)
  2. Carotid Stenosis (Cerebrovascular Accident)
  3. Abdominal Aortic Aneurysm (9% comorbid Prevalence, 15.8% if age >75 years)
    1. Giugliano (2012) BMC Surg 12(Suppl 1): S17 [PubMed]

VI. Symptoms

  1. Presentations
    1. Classic Claudication: 10% of cases
    2. Atypical Leg Pain: 50% of cases
    3. Asymptomatic: 40% of cases
  2. Classic Claudication
    1. Cramp-like leg Muscle pain or Fatigue with Exercise, better with rest
      1. Calf pain typical (pain may occur in thigh, buttock)
    2. Pain worse with exertion
    3. Pain relieved within 10 minutes rest
    4. Pain relieved with rest and dependent position
  3. Critical Limb Ischemia (1% of presentations)
    1. Tissue loss or gangrene
    2. Burning pain or numbness in the forefoot may awaken patient
    3. Pain improves with hanging leg over the side of the bed (with dependent redness or rubor)
    4. Chronic (>2 weeks) ischemic rest pain, often occurring soon after falling asleep
      1. Chronicity allows for collateral vessel development and preserved limb viability despite severe symptoms
  4. Acute Limb Ischemia (see management below)
    1. Cold, painful, pale limb with diminished or absent pulses
    2. Motor weakness
    3. Decreased Sensation
    4. Abrupt onset allows for no collateral circulation, and a short window of viable tissue for revascularization
  5. Timing of symptoms related to degree of stenosis
    1. Exertional pain: 70% arterial pain
    2. Nocturnal pain: 70 to 90% arterial stenosis
    3. Ischemic rest pain: 90% arterial stenosis

VII. Exam

  1. Vascular Exam (Arterial Bruits or diminished pulses)
    1. Abdominal aorta bruit
    2. Femoral artery bruit
    3. Femoral artery pulse
    4. Dorsalis pedis pulse (absent in up to 3% of normal patients)
    5. Posterior tibial pulse
    6. Carotid Artery pulse and bruit (for comorbid Carotid Stenosis)
  2. Neurologic Exam
    1. Critical in determining Acute Limb Ischemia degree (see Rutherford Classification below)
    2. Extremity Motor Exam
    3. Extremity Sensory Exam

VIII. Signs

  1. Most reliable signs of Peripheral Vascular Disease (Sensitivity, Specificity assumes ABI<0.9)
    1. Posterior tibial artery Doppler Ultrasound
      1. All 3 components present rules-out Peripheral Arterial Disease
      2. Only 1 of 3 components present is strongly suggestive of PAD (Positive Likelihood Ratio = 7.0)
    2. Dorsalis pedis AND posterior tibial pulse absent
      1. Test Sensitivity: 63%
      2. Test Specificity: 99%
    3. Femoral artery bruit
      1. Test Sensitivity: 29%
      2. Test Specificity: 95%
    4. Atypical Skin Color (pale, red, blue) of extremity
      1. Test Sensitivity: 35%
      2. Test Specificity: 87%
  2. Local Signs of Peripheral Vascular Disease
    1. Dry, scaly, shiny atrophic skin
    2. Skin hairless over lower extremity (e.g. shin)
    3. Dystrophic, brittle Toenails
    4. Non-healing ulcers or other lower extremity wounds
      1. See Arterial Ulcer
      2. Ulcers are well-demarcated and appear to be "punched out"
    5. Decreased skin Temperature (cool feet)
    6. Decreased Capillary Refill Time
    7. Distal extremity color change with position
      1. Skin rubor when leg dependent
      2. Skin pallor when leg elevated >1 minute
        1. Color returns within 15 seconds in mild cases
        2. Delay >40 seconds suggests severe ischemia

IX. Signs: Acute Limb Ischemia (5 P's)

  1. Early finding
    1. Pain
  2. Late findings
    1. Pulselessness
    2. Pallor
    3. Paresthesias
    4. Paralysis

X. Signs: Occlusion Location

  1. Inflow Disease: Aortoilliac Occlusive Disease
    1. Also known as Leriche's Syndrome
    2. Bilateral leg diminished pulses throughout
    3. Slow Wound Healing legs
    4. Impotence
  2. Outflow Disease
    1. Iliofemoral Occlusive Disease
      1. Unilateral leg diminished pulses throughout
      2. Buttock Claudication may be present
    2. Femoropopliteal Occlusive Disease
      1. Thigh and calf Claudication
      2. Normal femoral pulses in groin

XI. Classification

  1. Rutherford Classification of Acute Limb Ischemia
    1. Category I: Viable (no immediate threat)
      1. No sensory deficit
      2. No motor deficit
      3. Arterial doppler audible but typically monophasic (but venous doppler audible)
    2. Category IIA: Marginally threatened (salvageable if promptly treated)
      1. Minimal sensory deficit (e.g. toes involved)
      2. No motor deficit
      3. Arterial doppler inaudible (but venous doppler audible)
    3. Category IIB: Immediately Threatened (salvageable if immediately revascularized)
      1. Sensory deficit with rest pain
      2. Mild to moderate motor deficit
      3. Arterial doppler inaudible (but venous doppler audible)
    4. Category III: Irreversible (major tissue loss with permanent nerve injury)
      1. Severe sensory deficit with complete Anesthesia
      2. Severe motor deficit with paralysis or rigor
      3. Arterial doppler inaudible (but venous doppler audible)
  2. Fontaine Stage
    1. Stage I: Asymptomatic
      1. Ankle-Brachial Index < 0.9
      2. Decreased distal pulses
    2. Stage II: Intermittent Claudication
    3. Stage III: Daily rest pain
    4. Stage IV: Focal tissue necrosis (non-healing ulcers)
      1. Ankle-Brachial Index < 0.3 (50% block)
  3. Grading Claudication
    1. Initial Claudication Distance
      1. Distance patient first experiences exertional pain
    2. Absolute Claudication Distance
      1. Furthest distance patient is able to walk

XII. Differential Diagnosis

  1. See Leg Pain
  2. See Hip Pain
  3. See Knee Pain
  4. See Foot Pain
  5. Common and important other Leg Pain causes
    1. Lumbar Spinal Stenosis (Pseudoclaudication)
    2. Peripheral Neuropathy (e.g. Diabetic Neuropathy)
    3. Nerve Entrapment (e.g. Meralgia Paresthetica, Posterior Tarsal Tunnel Syndrome)
    4. Night Cramps
    5. Exertional Compartment Syndrome (or Chronic Compartment Syndrome)
    6. Stress Fracture
    7. Arthritis
    8. Intermittent Claudication (Peripheral Vascular Disease)
    9. Deep Vein Thrombosis (DVT)
    10. Venous Insufficiency
  6. Acute Limb Ischemia differential diagnosis
    1. Congestive Heart Failure with superimposed PVD
      1. Identical presentation to limb ischemia
    2. Deep Venous Thrombosis
      1. Blue extremity without pallor
      2. Swollen, painful extremity
    3. Acute Spinal Cord Compression
      1. Skin Color normal
      2. Limb paralysis with pain and Paresthesias
  7. Acute Limb Ischemia sites of compromise proximal to extremity
    1. Thoracic Aortic Dissection
    2. Abdominal Aortic Aneurysm (AAA)
    3. Embolic phenomenon from a cardiac source

XIII. Labs

  1. Complete Blood Count with Platelets
  2. Lipid profile
  3. Serum Homocysteine
  4. Apolipoprotein A
  5. Serum Creatinine
  6. Hemoglobin A1C or Fasting Serum Glucose
  7. Urinalysis for glucosuria or Proteinuria
  8. Consider screening for Hypercoagulability

XIV. Diagnosis

  1. See Edinburgh Claudication Questionnaire
  2. See PAD Score
  3. See Segmental Arterial Pressure
  4. Ankle-Brachial Index
    1. ABI is the Vital Sign of Peripheral Arterial Disease
    2. Obtain for diagnosis and monitor periodically for disease progression
    3. Ankle-Brachial Ratio >1.4: Non-compressable vessels (False Negative)
    4. Ankle-Brachial Ratio >0.9: Normal
    5. Ankle-Brachial Ratio <0.5: Severe, multi-level disease
    6. Ankle-Brachial Ratio <0.3: Limb Threatening Ischemia (requires emergent intervention)
    7. Ankle-Brachial Ratio <0.2: Gangrenous extremity
  5. Alternative Studies
    1. Toe-Brachial Ratio
      1. Typically 0.7 to 0.8
      2. Abnormal <0.7 (severe if <0.4)
    2. Exercise ABI Testing
      1. Obtain ABI immediately after walking 5 minutes on treadmill at 12% grade and 2.0 miles/h OR
      2. Symptoms require patient to stop
    3. Six-Minute Walk Test

XV. Imaging

  1. Ultrasound
    1. Ultrasound Ankle-Brachial Index
    2. Segmental Arterial Doppler Ultrasound
    3. Abdominal Aorta Ultrasound
      1. Consider at time of periperal arterial disease diagnosis (due to association with AAA)
  2. CT Angiography
    1. CTA Abdomen and Pelvis with limb runoff
    2. Preferred definitive study in Acute Limb Ischemia

XVI. Screening: Indications with Ankle-Brachial Index

  1. Guidelines vary per organization
    1. USPTF does not recommend routine screening unless symptomatic
      1. Symptom Example: Exertional Leg Pain or non-healing distal extremity wounds
    2. Cardiovascular Risk Reduction even without PAD diagnosis will benefit PAD in addition to other vascular disease
  2. Diabetes Mellitus (ADA, ACC/AHA)
    1. Start at age 50 years or earlier if other comorbid PAD Risk Factors
      1. Other example risks: Tobacco Abuse, Hyperlipidemia, Diabetes Mellitus >10 years
    2. Repeat every 5 years
  3. Age over 65 years old (ACC/AHA)
  4. Age 50 to 64 years old AND atherosclerosis risks (Hypertension, Diabetes Mellitus, Hyperlipidemia, Tobacco, FHx PAD)
  5. Known vascular disease affecting another system (e.g. AAA, Carotid Stenosis, Coronary Artery Disease, Mesenteric Ischemia)

XVII. Grading

  1. History
    1. Degree of extremity pain
    2. Pain-free walking distance
  2. Questionaires (e.g. Walking Impairment Questionaire)
  3. Treadmill testing
    1. Maximal walking distance
    2. Pain-free walking distance

XVIII. Course

  1. Typical course of non-critical ischemia
    1. Claudication remains stable in 80% of patients
    2. Five year risk of Claudication worsening: 16%
    3. Claudication requiring surgery: 25%
  2. Risk of limb loss (amputation)
    1. Stable non-critical ischemia
      1. Risk at five years: 4-7%
      2. Risk at ten years: 12%
    2. Critical Limb Ischemia
      1. Risk at 6-12 months from onset: 80-90%
  3. Five year Mortality from atherosclerotic cause: 29%
    1. Coronary Artery Disease deaths: 60%
    2. Cerebrovascular Accident related deaths: 15%
  4. Overall survival
    1. Survival at ten years: 38%
    2. Survival at fifteen years: 22%

XIX. Management

  1. Acute Limb Ischemia (Emergency management)
    1. See Acute Limb Ischemia
  2. Chronic Claudication
    1. See Peripheral Vascular Disease Management (Claudication Management)
    2. Cardiovascular Risk Reduction is critical
      1. PAD carries same risk as Coronary Artery Disease

XX. Prognosis

  1. See Peripheral Arterial Disease 10-Year Mortality Index
  2. Intermittent Claudication progresses to Critical Limb Ischemia in 21% of cases
  3. Critical Limb Ischemia is associated with a 25% annual mortality rate (esp. due to cardiovascular cause)

XXI. Resources

  1. Vascular Disease Foundation
    1. http://www.vdf.org

XXII. References

  1. Boccalon (1999) Drugs Aging 14:247
  2. Broder (2024) Crit Dec Emerg Med 38(4): 23-4
  3. Boyd (1962) Proc R Soc Med 55:591-96 [PubMed]
  4. Carman (2000) Am Fam Physician 61(4):1027-32 [PubMed]
  5. Firnhaber (2019) Am Fam Physician 99(6): 362-9 [PubMed]
  6. Firnhaber (2022) Am Fam Physician 105(1): 65-72 [PubMed]
  7. Gardner (1995) JAMA 274(12):975-80 [PubMed]
  8. Gey (2004) Am Fam Physician 69:525-33 [PubMed]
  9. Hennion (2013) Am Fam Physician 88(5): 306-10 [PubMed]
  10. Hirsch (2001) JAMA 286(11):1317-24 [PubMed]
  11. Imparato (1975) Surgery 78:795-9 [PubMed]
  12. Samuelson (March, 2000) Fed Pract, p. 34-50
  13. Santilli (1999) Am Fam Physician 59(7):1899-908 [PubMed]
  14. Santilli (1996) Am Fam Physician 53(4):1245-53 [PubMed]
  15. Sontheimer (2006) Am Fam Physician 73(11):1971-6 [PubMed]
  16. (1999) Med Lett Drugs Ther 41:(1052):44-6 [PubMed]

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