August 2020

An Update on Peripheral Artery Disease (PAD): Part I #1139100179

This 2-part series examines the current state of peripheral artery disease. This article focuses on disease burden, risk factors, and clinical presentation. Part 2, which will appear next month, will examine current recommendations for diagnosis and treatment.

By Aisha Cobbs, PhD

Peripheral artery disease (PAD) is a widespread chronic condition that is most commonly characterized by atherosclerosis, or blockages, in the arteries supplying blood to lower extremities, such as legs, feet, and toes. It is an indicator of systemic atherosclerosis and is a major risk factor for coronary artery disease, myocardial infarction, and stroke.1

PAD is a global problem, affecting more than 200 million patients worldwide.2 Prevalence estimates for  PAD vary widely from approximately 8.5 million3 to 21 million Americans4 ≥40 years of age. Despite increasing prevalence, PAD continues to be underrecognized because, in many patients, symptoms may not appear until advanced stages of the disease.5

Risk Factors

Major risk factors for PAD include age > 65 years, hypertension, diabetes mellitus, chronic kidney disease, hyperlipidemia, and smoking (Table 1).6,7 Individuals with at least 3 or more of these factors have a 10-fold risk for developing PAD.8

Morbidity and mortality rates associated with PAD are similar or higher to those associated with coronary heart disease.9 Evidence suggests that the earlier detection of PAD can reveal the extent to which patients are at increased risk for complications of atherosclerotic cardiovascular disease, including coronary artery disease, myocardial infarction, and stroke.10 Thus, screening is recommended in patients at risk for PAD to improve patient outcomes (Table 2).1,7

“Individuals with at least 3 or more of these factors have a 10-fold risk for developing PAD.”

Clinical Presentation

Intermittent claudication, the classical symptom of PAD, is defined as leg discomfort while walking that improves at rest.6 It typically manifests as a consistent throbbing soreness in the calves, thighs, buttocks, hips or feet. The cause of this discomfort is the result of insufficient blood flow to the lower extremities causing a lack of oxygen to the muscles required for walking and exercise.5

As PAD continues to progress, the discomfort of intermittent claudication becomes more severe, and takes less exertion to trigger the discomfort.6 As blood flow continues to be further constricted, patients will begin to experience lower extremity discomfort at rest. This discomfort is typically experienced in the feet first, and often at night, because leg elevation decreases blood flow. When a patient is experiencing leg discomfort at rest related to PAD, the patient is considered to have an advanced form of PAD called critical limb ischemia (CLI), which is associated with increased cardiovascular risk.12

The body needs oxygenated blood flowing to the extremities to ensure proper tissue viability and enable the proper recovery from cuts, blisters, or other minor wounds. If lower extremity blood flow is compromised, a wound on that extremity will typically be slow to heal, increasing the risk of infection.13 If a wound that is infected is not properly treated, the infection causes localized death and decomposition of tissue at the wound site, commonly referred to as gangrene. A wound that has progressed to gangrene typically requires amputation to stop the progression of gangrene to other parts of the body. Smoking and elevated hemoglobin A1C levels increase the risk of amputation in patients with PAD.13

Approximately 50% of patients with PAD present with atypical symptoms or do not have the traditional symptoms of PAD, but studies suggest that whether or not a patient with PAD is presenting with typical symptoms does not have an impact on PAD-related mortality.6,14

Barriers to Early Diagnosis

PAD, particularly when it is advanced, is associated with increased morbidity and mortality. Therefore, early diagnosis is critical to reduce the patient’s cardiovascular risk and to preserve their limbs and quality of life. However, common PAD symptoms are typically underreported, especially in patients with a sedentary lifestyle who are not moving to the point of producing symptoms such as intermittent claudication, or discomfort while walking. Others may attribute aches and pains to natural aging. Because of this, a patient may experience symptoms of PAD for a long period of time before reporting them to a healthcare provider.

Even still, PAD may go undetected by healthcare providers for many reasons. They may discount reported symptoms or assume symptoms, such as pain while walking, may be due to arthritis or a musculoskeletal issue, particularly in elderly patients.15 Although the discomfort experienced with intermittent claudication is typically cramp-like uneasiness, it can sometimes be experienced as fatigue, weariness, numbness or tingling, causing PAD symptoms to be misidentified by a healthcare provider.

Increasing awareness of PAD among clinicians and patients is the first step in limb preservation and reducing the risk of cardiovascular deaths associated with PAD. In Part 2 of this series on peripheral artery disease, we will review diagnostic testing for PAD and current treatment options for this stealthy disease.

  1. Aboyans V, Ricco JB, Bartelink MEL, et al. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries. Endorsed by: the European Stroke Organization (ESO), The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS). Eur Heart J. 2018;39(9):763-816.
  2. Bevan GH, White Solaru KT. Evidence-Based Medical Management of Peripheral Artery Disease. Arterioscler Thromb Vasc Biol. 2020;40(3):541-553.
  3. Virani SS, Alonso A, Benjamin EJ, et al. Heart Disease and Stroke Statistics-2020 Update: A Report From the American Heart Association. Circulation. 2020;141(9):e139-e596.
  4. Yost M. Critical Limb Ischemia Volume I, United States Epidemiology, Supplement 2016. Atlanta, GA: The Sage Group; 2016.HCUP Nationwide Inpatient Sample (NIS). Healthcare Cost and Utilization Project (HCUP). Rockville, MD: Agency for Healthcare Research and Quality; 2009.
  5. McDermott MM. Lower extremity manifestations of peripheral artery disease: the pathophysiologic and functional implications of leg ischemia. Circ Res. 2015;116(9):1540-1550.
  6. Firnhaber JM, Powell CS. Lower Extremity Peripheral Artery Disease: Diagnosis and Treatment. Am Fam Physician. 2019;99(6):362-369.
  7. 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):e726-e779.
  8. Eraso LH, Fukaya E, Mohler ER III et al. Peripheral arterial disease, prevalence and cumulative risk factor profile analysis. Eur J Prev Cardiol. 2014; 21(6): 704-711.
  9. Agnelli G, Belch JJF, Baumgartner I, et al. Morbidity and mortality associated with atherosclerotic peripheral artery disease: A systematic review. Atherosclerosis. 2020;293:94-100.
  10. Liu H, Wang H. Early Detection System of Vascular Disease and Its Application Prospect. Biomed Res Int. 2016;2016:1723485.
  11. American Diabetes Association. Peripheral Arterial Disease in People With Diabetes. Diabetes Care. 2003;26(12):3333-3341.
  12. Bailey MA, Griffin KJ, Scott DJ. Clinical assessment of patients with peripheral arterial disease. Semin Intervent Radiol. 2014;31(4):292-299.
  13. Olivieri B, Yates TE, Vianna S, et al. On the Cutting Edge: Wound Care for the Endovascular Specialist. Semin Intervent Radiol. 2018;35(5):406-426.
  14. Diehm C, Allenberg JR, Pittrow D, et al. Mortality and vascular morbidity in older adults with asymptomatic versus symptomatic peripheral artery disease. Circulation. 2009;120(21):2053-2061.
  15. Aronow H. Peripheral arterial disease in the elderly: recognition and management. Am J Cardiovasc Drugs. 2008;8(6):353-364.

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