Peripheral arterial disease

Peripheral arterial disease (PAD) is characterized by narrowing and, in final stages, occlusion of the peripheral arteries due to atherosclerotic plaques. Smoking is the most important risk factor for developing PAD. PAD is often a silent disease, but patients may present with features of arterial insufficiency (intermittent claudication, reduced temperature and pulse rate in affected limb, skin discoloration, and trophic changes). On occasion, critical limb ischemia is the only presenting complaint. Segmental blood pressures and pulse volume recordings, particularly the ankle-brachial index (ABI), may support the diagnosis. Further imaging may confirm and assess the location and severity of arterial stenosis or occlusion. Treatment focuses on smoking cessation, graduated exercise, avoiding extremely cold temperatures, and modifying other cardiovascular risk factors. If conservative treatment fails, interventional and surgical management is recommended for low-risk patients with potential long-term success.

• Prevalence: 8.5 million in the US
  • Prevalence increases with age, starting from the age of 40
  • US incidence rates are highest among African Americans, followed by Hispanics, who are at a slightly higher risk than non-hispanic whites.
• Peak incidence: 60–80 years of age
• Sex: ♂ = ♀

References:^[1][2]

Epidemiological data refers to the US, unless otherwise specified.

• Insufficient tissue perfusion due to atherosclerosis in the aorta and peripheral arteries
• Often coexists with coronary artery disease (CAD), stroke, atrial fibrillation, and renal disease
• See risk factors for atherosclerosis

PAD usually coexists with coronary artery disease. Smoking is the most important risk factor for PAD!
References:^[3]

References:^[4]

A bruit, suggestive of arterial stenosis, may be heard in > 60–70% of cases with PAD!

References:^[5][6][7][8]

Ankle-brachial index (ABI)

• First-line diagnostic test (high specificity and sensitivity) ^[9]
• Defined as the ratio of systolic ankle blood pressure (BP) to systolic brachial BP
• The ABI is calculated for each leg by dividing the higher systolic pressure of either the dorsalis pedis or posterior tibialis of the respective leg by the higher blood pressure of either the right or left arm
  • Right ABI = highest systolic BP in the right ankle/brachial BP in the arm with the highest systolic pressure
  • Left ABI = highest systolic BP in the left ankle/brachial BP in the arm with the highest systolic pressure
• Normally, ankle BP and brachial BP are equal (ABI = 1), or ankle BP is only slightly higher because of gravity (ABI > 1)
• Differences in systolic BP indicate different pathologies:
  • > 1.3 = medial sclerosis with incompressible vascular wall (generally calcified vessels)
  • 1.0–1.30 = normal value
  • 0.91–0.99 = borderline
  • 0.40– 0.90 = mild to moderate PAD → claudication
  • < 0.40 = severe PAD → resting pain, gangrene (critical limb ischemia)
• Exercise testing may be required if patients have a normal resting ABI ^[10]

Imaging

While vascular imaging is not necessarily required for diagnosis, it is useful to determine the site and severity of arterial stenosis or occlusion (especially preoperatively and postoperatively)

• Color-coded duplex ultrasonography
• Digital subtraction angiography (DSA): gold standard
• CT angiography
• MR angiography
• Oscillography

ABI measurements in diabetic or older patients may be inaccurate because of Monckeberg sclerosis!

References:^[11][12][13]

The differential diagnoses listed here are not exhaustive.

Conservative ^[13]

• Smoking cessation!
• Supervised graded exercise therapy
• Foot care (especially in diabetic patients)
• Avoid cold temperatures

Medical therapy

• Modify cardiovascular risk factors: see therapy of atherosclerotic disease
  • Antiplatelet therapy reduces morbidity and mortality
    • Aspirin: irreversible cyclooxygenase inhibition → decreased thromboxane A2 synthesis → decreased platelet aggregation
    • ADP receptor inhibitors
      • Clopidogrel: inhibition of the P2Y₁₂ ADP receptor → decreased platelet activation and platelet-fibrin crosslinking
      • Ticagrelor; : reversible inhibition of the P2Y₁₂ ADP receptor (otherwise identical downstream effects as clopidogrel)
  • Lipid-lowering agent (usually statins)
  • Antihypertensive treatment
  • Hyperglycemia control
• PDE inhibitors
  • Cilostazol (the single most effective medication)
    • It is indicated in patients with lifestyle-limiting intermittent claudication; only after 3 months of supervised graded exercise therapy.
    • It is administered as a therapeutic trial for 3–6 months.
    • If no or minimal improvement occurs, consider advanced vascular imaging (see “Imaging” above).
    • Mechanisms
      • Phosphodiesterase 3 (PDE3) inhibition → increased cAMP → increased activity of protein kinase A → reduced platelet aggregation
      • Myosin light chain kinase inhibiton → vascular smooth muscle relaxation → arterial vasodilation

Revascularization^[15]

• Indications ^[11]
  • Critical limb ischemia
  • Failure of conservative and pharmacologic treatment
  • Inability to perform normal work or activities because of claudication
  • No limitations to exercise by other disease (e.g., chronic heart failure) if claudication is improved
  • Anatomy of the lesion allows low-risk and long-term success of intervention
• Minimally invasive interventional radiology: percutaneous transluminal angioplasty (PTA) with or without stenting
• Surgical procedures
  • Operative vascular reconstruction (bypass surgery): an autologous vein (e.g., great saphenous vein) is used to bypass the stenosis
  • Endarterectomy

Amputation

• Last resort in the event of gangrene

References:^{[6][7][11][13][15][16]}

• Arterial ulcer
  • Definition: skin defect due to impaired blood flow to the lower extremities
  • Etiology: most often seen in peripheral arterial disease
  • Clinical features
    • Punched-out ulcer with well-defined borders ^[17]
    • Usually involves the foot, particularly pressure points (e.g., lateral malleolus, tips of the toes)
    • Often severe pain ^[18]
  • Differential diagnosis: venous ulcer
• Infection of ulcers; sepsis
• Acute limb ischemia
• Complications of endovascular intervention: see “Complications at the site of vascular access”
• Surgical complications: bleeding, infection of vascular prosthesis, relapse

We list the most important complications. The selection is not exhaustive.

• Intermittent claudication → good prognosis
• Rest pain and/or ischemic ulcers → poor prognosis
• Increased cardiovascular mortality → high risk for secondary MI or stroke

A low ABI in PAD is also predictive of an increased risk of all-cause and cardiovascular mortality! ^[5]

See primary and secondary prevention of atherosclerosis.

• One-Minute Telegram 6-2020-3/3: Statins underprescribed in patients with PAD

Interested in the newest medical research, distilled down to just one minute? Sign up for the One-Minute Telegram in “Tips and links” below.

1. Peripheral Arterial Disease (PAD) Fact Sheet. http://www.cdc.gov/dhdsp/data_statistics/fact_sheets/fs_pad.htm. Updated: June 16, 2016. Accessed: December 8, 2016.
2. Harris L, Maciej D, Mills JL, Eidt JF, Mohler III ER, Collins KA. Epidemiology, risk factors, and natural history of peripheral artery disease. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/epidemiology-risk-factors-and-natural-history-of-peripheral-artery-disease?source=see_link.Last updated: May 9, 2016. Accessed: December 8, 2016.
3. Hayward RA, Elmore JG, Collins KA. Screening for lower extremity peripheral artery disease. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/screening-for-lower-extremity-peripheral-artery-disease.Last updated: March 5, 2015. Accessed: December 8, 2016.
4. Mills JL, Eidt JF, Collins KA. Classification of lower extremity peripheral artery disease. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/classification-of-lower-extremity-peripheral-artery-disease?source=search_result&search=peripheral%20artery%20disease&selectedTitle=9~150.Last updated: July 18, 2016. Accessed: December 8, 2016.
5. Park CW, Peter K. Ankle-Brachial Index Measurement. Ankle-Brachial Index Measurement. New York, NY: WebMD. http://emedicine.medscape.com/article/1839449-overview#a3. Updated: October 13, 2016. Accessed: December 8, 2016.
6. Neschis DG, Golden MA, Eidt JF, Mills JL, Clement DL, Mohler III ER, Collins KA. Clinical features and diagnosis of lower extremity peripheral artery disease. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-lower-extremity-peripheral-artery-disease?source=search_result&search=leriche%20syndrome&selectedTitle=1~2.Last updated: June 12, 2014. Accessed: December 8, 2016.
7. Minar E. Critical limb ischaemia. Hamostaseologie.. 2009; 29 (1): p.102-109.
8. Neschis DG, Golden MA, Eidt JF, Mills JL Sr, Collins KA. Treatment of Chronic Lower Extremity Critical Limb Ischemia. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/treatment-of-chronic-lower-extremity-critical-limb-ischemia?source=see_link#H2.Last updated: July 17, 2015. Accessed: August 25, 2017.
9. Slovut DP, Sullivan TM. Critical limb ischemia: medical and surgical management. Vasc Med. . 2008; 13 (3): p.281-291. doi: 10.1177/1358863X08091485. . | Open in Read by QxMD
10. Gerhard-Herman MD, Gornik HL, Barrett C, et al. 2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2017; 135 (12). doi: 10.1161/cir.0000000000000471 . | Open in Read by QxMD
11. Hirsch AT et al. ACC/AHA 2005 Practice Guidelines for the Management of Patients With Peripheral Arterial Disease (Lower Extremity, Renal, Mesenteric, and Abdominal Aortic). Circulation. 2006; 113 : p.e463-e654. doi: 10.1161/CIRCULATIONAHA.106.174526 . | Open in Read by QxMD
12. Mitchell E, Eidt JF, Mills JL, Mohler III ER, Collins KA. UpToDate. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/noninvasive-diagnosis-of-arterial-disease?source=see_link§ionName=Ankle-brachial%20index&anchor=H58544655#H58544655.Last updated: September 28, 2016. Accessed: December 8, 2016.
13. Kasper DL, Fauci AS, Hauser SL, Longo DL, Lameson JL, Loscalzo J. Harrison's Principles of Internal Medicine. McGraw-Hill Education ; 2015
14. Kawarai S, Fukusawa M, Kawahara Y. Adventitial Cystic Disease of the Popliteal Artery. Ann Vasc Dis. 2012; 5 : p.190-193. doi: 10.3400/avd.cr.11.00069 . | Open in Read by QxMD
15. Neschis DG, Golden MA, Eidt JF, Mills JL, Mohler III ER, Clement DL, Collins KA. Surgical management of claudication. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/surgical-management-of-claudication?source=search_result&search=peripheral%20arterial%20disease%20treatment&selectedTitle=5~150.Last updated: April 8, 2016. Accessed: December 8, 2016.
16. Mohler III ER, Davies MG, Clement DL, Eidt JF, Mills JL, Collins KA. Management of claudication. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/management-of-claudication?source=search_result&search=peripheral%20arterial%20disease%20treatment&selectedTitle=6~150.Last updated: October 17, 2016. Accessed: December 8, 2016.
17. Arterial Ulcers. http://www.woundsource.com/patientcondition/arterial-ulcers. Updated: March 8, 2017. Accessed: March 8, 2017.
18. Alguire PC, Mathes BM, Eidt JF, Mills JL, Collins KA. Clinical manifestations of lower extremity chronic venous disease. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/clinical-manifestations-of-lower-extremity-chronic-venous-disease?source=see_link#H6.Last updated: August 17, 2015. Accessed: December 7, 2016.
19. Herold G. Internal Medicine. Herold G ; 2014