Peripheral arterial disease history and symptoms
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Peripheral arterial disease Microchapters |
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Differentiating Peripheral arterial disease from other Diseases |
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Diagnosis |
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Treatment |
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Case Studies |
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AHA/ACC Guidelines on Management of Lower Extremity PAD |
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Guidelines for Structured Exercise Therapy for Lower Extremity PAD |
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Guidelines for Minimizing Tissue Loss in Lower Extremity PAD |
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Guidelines for Revascularization of Claudication in Lower Extremity PAD |
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Guidelines for Management of Acute Limb Ischemial in Lower Extremity PAD |
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Guidelines for Longitudinal Follow-up for Lower Extremity PAD |
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Peripheral arterial disease history and symptoms On the Web |
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American Roentgen Ray Society Images of Peripheral arterial disease history and symptoms |
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Peripheral arterial disease history and symptoms in the news |
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Directions to Hospitals Treating Peripheral arterial disease |
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Risk calculators and risk factors for Peripheral arterial disease history and symptoms |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Basir Gill, M.B.B.S, M.D.[2] Cafer Zorkun, M.D., Ph.D. [3] Vishnu Vardhan Serla M.B.B.S. [4] Rim Halaby
Overview
The clinical presentation of peripheral arterial disease (PAD) can be categorized into four clinical subsets: asymptomatic PAD, chronic symptomatic PAD (including claudication), chronic limb-threatening ischemia (CLTI), and acute limb ischemia (ALI). Patients may move between these subsets over time, such as deterioration from chronic symptomatic PAD to CLTI or ALI, or improvement after treatment.
Depending on the population assessed and method of assessment, 20%-59% of patients with objectively proven PAD report no leg symptoms. Among those with symptoms, exertional leg symptoms (typical claudication or other) are reported in up to 80% of patients, though only approximately one-third present with classic claudication. The hallmark symptom of PAD is claudication, an intermittent cramping pain in the leg induced by exercise and relieved by rest, typically within approximately 10 minutes. However, leg symptom descriptors also include tingling, numbness, burning, throbbing, or shooting sensations.
The clinical presentation depends on the location and severity of arterial stenosis. Calf cramping in the upper two-thirds of the calf is usually due to superficial femoral artery disease, while cramping in the lower one-third of the calf is due to popliteal artery disease. Buttock, thigh, calf, or foot claudication can occur either singly or in combination. Leg pain occurs in one leg in approximately 40% of patients and in both legs in approximately 60% of patients.
PAD affects an estimated 7 to 12 million individuals in the United States and approximately 200 million people worldwide. PAD is uncommon before age 50 years and affects approximately 20% of people aged 80 years and older. The prevalence of PAD is nearly twice as high in Black individuals compared with White persons, and lifetime risks of PAD are 30% in Black men, 27.6% in Black women, approximately 22% in Hispanic men and women, and 19% in White men and women. Women and Black patients have a higher prevalence of atypical leg symptoms and asymptomatic PAD, which may lead to underdiagnosis in these populations.
Clinical Subsets of PAD
The 2024 ACC/AHA Guideline defines four clinical subsets of PAD:
Asymptomatic PAD (may have functional impairment): 20%-59% of patients with objectively proven PAD report no leg symptoms. Patients may self-limit activity to remain below their ischemic threshold. Asymptomatic patients have functional impairment comparable to patients with claudication and are at increased risk of MACE, including mortality.
Chronic Symptomatic PAD (includes claudication and other exertional leg symptoms): The most common clinically evident subset. Typical claudication is described as pain, aching, cramping, or tired/fatigued feeling in the buttock, thigh, calf, or foot that occurs consistently during walking, does not start at rest, does not improve during walking, and is usually relieved within approximately 10 minutes of rest. Leg symptom descriptors also include tingling, numbness, burning, throbbing, or shooting.
CLTI: Incidence estimated at 11%-20% among patients with known PAD. Manifests as ischemic rest pain, nonhealing wounds/ulcers, or gangrene with symptoms present for >2 weeks. Historically estimated 1-year mortality rate of 25%-35% and 1-year rate of amputation up to 30%. Ischemic rest pain often affects the forefoot and is worsened with limb elevation and relieved by dependency.
ALI: Incidence of 1.7% (0.8/100 patient-years) in a contemporary RCT. Sudden decrease in arterial perfusion threatening limb viability.[1]
History
An accurate history is the key to the diagnosis of PAD. The 2024 ACC/AHA Guideline recommends that in patients at increased risk of PAD, a comprehensive medical history and review of symptoms should be performed to assess for exertional leg symptoms, lower extremity rest pain, and lower extremity wounds or other ischemic skin changes (Class 1, Level of Evidence B-NR).
The history must include information about:
- Any exertional limitation of the lower extremity muscles or any history of walking impairment (fatigue, numbness, aching, or pain).
- Detailed description of claudication symptoms:
- Pain type: Aching, burning, cramping, discomfort, or fatigue.
- Location: Buttock, thigh, calf, or ankle.
- Onset/offset: Distance, exercise, uphill walking; how long for relief after rest (typically 10 minutes rest to resolve.
- Leg weakness, numbness, or fatigue during walking without pain. Any pain at rest localized to the lower leg or foot and its association with the upright or recumbent positions (ischemic rest pain often affects the forefoot and is worsened with limb elevation and relieved by dependency).
- Atherosclerotic risk factors: older age, diabetes mellitus, cigarette smoking, hypertension, dyslipidemia, elevated inflammatory biomarker levels, lipoprotein(a), and certain genetic markers. Risk of PAD persists 20 to 30 years after smoking cessation. Compared with people without diabetes, those with it have a 2- to 4-fold higher risk of PAD.
- Any poorly healing or nonhealing ulcers of the legs or feet.
- Erectile dysfunction.
- Postprandial abdominal pain that reproducibly is provoked by eating and is associated with weight loss (suggestive of mesenteric ischemia).
- Family history of a first-degree relative with abdominal aortic aneurysm.
- History of atherosclerotic disease in other vascular beds (coronary artery disease, cerebrovascular disease).
History and Physical Examination Findings Suggestive of PAD
The following findings are suggestive of PAD, adapted from the 2024 ACC/AHA Guideline (Table 6):
History findings:
- Claudication: Pain type includes aching, burning, cramping, discomfort, or fatigue; location includes buttock, thigh, calf, or ankle; onset/offset related to distance, exercise, uphill walking, with relief after rest (typically 10 min rest to resolve; leg weakness, numbness, or fatigue during walking without pain.
- Ischemic rest pain: Pain at rest in the forefoot, worsened with elevation, relieved by dependency.
- Wound history: Nonhealing or slow-healing lower extremity wound.
- Erectile dysfunction: May indicate aortoiliac disease.
Physical examination findings:
- Pulse abnormalities: Abnormal lower extremity pulse palpation (femoral, popliteal, dorsalis pedis, or posterior tibial arteries).
- Vascular bruit: Epigastric, periumbilical, or groin bruit.
- Wound/gangrene: Nonhealing lower extremity wound; lower extremity gangrene.
- Other ischemic signs: Asymmetric hair growth, nail bed changes, calf muscle atrophy, elevation pallor/dependent rubor.
Screening Questionnaires
The Edinburgh Claudication Questionnaire (ECQ) is an improved version of the WHO/Rose Questionnaire developed for use in epidemiological surveys. In its original validation, the ECQ was found to be 91.3% sensitive (95% CI 88.1%-94.5%) and 99.3% specific (95% CI 98.9%-100%) for intermittent claudication compared with physician diagnosis, with excellent 6-month repeatability (kappa = 0.76).[2] However, when validated against duplex ultrasound as a reference standard in general practice, the ECQ had a sensitivity of 52.5% (95% CI 42.3%-62.5%) and specificity of 87.1% (95% CI 80.6%-92.0%), suggesting relatively poor diagnostic accuracy in isolation.[3]
Symptoms
Asymptomatic PAD
Depending on the population assessed, 20%-59% of patients with objectively proven PAD report no leg symptoms. Patients classified as having asymptomatic PAD may self-limit and adapt their activity to remain below their ischemic threshold to avoid leg pain. A significant percentage of patients with asymptomatic PAD who report no exertional leg symptoms develop symptoms during an objective walking test. Importantly, patients with PAD who are asymptomatic have functional impairment comparable to patients with claudication and are at increased risk of major adverse cardiovascular events (MACE), including mortality.
Intermittent Claudication
Intermittent claudication is the most common clinically evident symptom of PAD. Typical claudication symptoms may be described as:
- Onset: Always after walking or exercise; does not start at rest; does not improve during walking
- Character: Pain, aching, cramping, burning, discomfort, or tired/fatigued feeling
- Location: Buttock, thigh, calf, or foot; unilateral or bilateral
- Walking distance: Symptoms occur at a relatively consistent walking distance
- Relief: Usually relieved within approximately 10 minutes of rest, without need to change position
- Other descriptors: Tingling, numbness, burning, throbbing, or shooting
For some patients, exertional leg symptoms due to PAD are not typical of claudication because they may not limit walking or may take >10 minutes to resolve after rest. Chronic symptomatic PAD is associated with significant functional (walking) impairment, regardless of whether symptoms are typical of claudication.
Chronic Limb-Threatening Ischemia (CLTI)
CLTI is the most severe chronic clinical subset of PAD. Among patients with known PAD, the incidence of CLTI is estimated to be between 11% and 20%. CLTI manifests as:
- Ischemic rest pain: Often affects the forefoot; worsened with limb elevation and relieved by dependency; symptoms present for >2 weeks
- Nonhealing wounds/ulcers
- Gangrene
CLTI is responsible for most major and minor limb amputations related to PAD. The historically estimated 1-year mortality rate is 25%-35% and the 1-year rate of amputation is up to 30% among patients presenting with CLTI.
Classification Systems for CLTI
Among vascular specialists, the Fontaine and Rutherford classification systems are most commonly used to categorize severity of PAD and CLTI:[4][5]
Fontaine Classification:
- Stage I: Asymptomatic
- Stage IIa: Mild claudication (able to walk >200 meters)
- Stage IIb: Moderate-severe claudication
Rutherford classification: Each component (wound, ischemia, infection) is graded as none, mild, moderate, or severe, and combined into four clinical stages:[6]
- Stage 1 (Very low): Predicted 1-year risk of major amputation 0%
- Stage 2 (Low): Predicted 1-year risk of major amputation 8% (95% CI 3%-21%)
- Stage 3 (Moderate): Predicted 1-year risk of major amputation 11% (95% CI 6%-18%)
- Stage 4 (High): Predicted 1-year risk of major amputation 38% (95% CI 21%-58%)
Acute Limb Ischemia (ALI)
ALI is one of the most treatable and potentially devastating presentations of PAD. It is defined as a sudden decrease in arterial perfusion of the leg that threatens the viability of the limb, with symptom duration ALI occurs in approximately 1.5 per 10,000 patients and is associated with up to 15% mortality.[7]
The classic presentation includes the 6 Ps:
- Pain
- Pallor
- Pulselessness
- Poikilothermia (coolness)
- Paraesthesias
- Paralysis
ALI is a medical emergency. The time constraint is attributable to the period that skeletal muscle will tolerate ischemia—approximately 4 to 6 hours. The longer symptoms are present, the less likely the possibility of limb salvage.
Rutherford Classification for ALI
The status of the limb in ALI is classified according to the Rutherford classification system:
- Category I — Viable: Limb not immediately threatened; no sensory loss; no motor deficit; arterial Doppler audible; venous Doppler audible.
- Category IIa — Marginally threatened: Salvageable if promptly treated; mild-to-moderate sensory loss (limited to toes); no motor deficit; arterial Doppler often inaudible; venous Doppler audible.
- Category IIb — Immediately threatened: Salvageable if urgently treated; sensory loss more than toes; mild-moderate motor weakness; arterial Doppler inaudible; venous Doppler audible.
- Category III — Irreversible: Major tissue loss or permanent nerve damage inevitable; complete sensory loss (anesthetic); complete paralysis; arterial Doppler inaudible; venous Doppler inaudible.
Causes of ALI include embolism, thrombosis within a native artery or at the site of previous revascularization (graft or stent), trauma, peripheral aneurysm with distal embolization, or thrombosis.
Other Symptoms of Advanced PAD
- Calf muscles that shrink (atrophy)
- Hair loss over the toes and feet (asymmetric hair growth)
- Thick toenails (nail bed changes)
- Shiny, tight skin
- Elevation pallor and dependent rubor
- Painful nonhealing ulcers on the feet or toes (usually black) that are slow to heal
Shown below is an image that summarizes the initial presentation of peripheral arterial disease:
Shown below is an image depicting the location of symptoms depending on the nature of involved arteries:
Leriche's Syndrome
Leriche's syndrome, an aortoiliac occlusive disease, is an atherosclerotic occlusive disease involving the abdominal aorta and/or both of the iliac arteries.[8]
The classical triad of symptoms of Leriche's syndrome:
- Claudication of the buttocks and thighs
- Absent or decreased femoral pulses
- Impotence
In addition, any number of symptoms may present depending on the distribution and severity of the disease, such as muscle atrophy and slow wound healing in the legs. Extensive collateral circulation may develop over time, including through the lower intercostal arteries connecting to the deep iliac circumflex and inferior epigastric arteries, and the arc of Riolan (a mesenteric collateral pathway).[9]
Differential Diagnosis of Leg Pain
The differential diagnosis for leg pain or claudication not related to PAD is broad. The following alternative diagnoses should be considered, adapted from the 2024 ACC/AHA Guideline (Table 7):
- Hip arthritis: Aching discomfort in the lateral hip and thigh; occurs after variable degree of exercise; not quickly relieved by rest; improved when not bearing weight; symptoms variable with history of degenerative arthritis.
- Foot/ankle arthritis: Aching pain in the ankle, foot, or arch; occurs after variable degree of exercise and may also be present at rest; not quickly relieved by rest; may be relieved by not bearing weight; symptoms variable.
- Nerve root compression: Sharp lancinating pain that radiates down the leg; induced by sitting, standing, or walking (variable); often present at rest; improved by change in position; history of back problems; worse with sitting; relief when supine or standing.
- Spinal stenosis (e.g., degenerative disc disease or tumor): Pain and weakness often in bilateral buttocks and posterior leg; may mimic claudication; variable relief with rest but can take a long time to recover; relief by lumbar spine flexion; worse with standing and extending spine.
- Symptomatic popliteal (Baker's) cyst: Swelling and tenderness behind the knee and down the calf; occurs with exercise; also present at rest; not intermittent.
- Venous claudication: Tight, bursting pain in the entire leg, worse in the calf; occurs after walking; subsides slowly; relief speeded by leg elevation; history of iliofemoral deep vein thrombosis; edema; signs of venous stasis.
- Chronic compartment syndrome: Tight, bursting pain in the calf muscles; occurs after strenuous exercise (jogging); subsides very slowly; relief with rest; typically in heavy muscled athletes.
The differentiation of neurogenic claudication from vasculogenic claudication is the most common clinical diagnostic challenge. In contrast to vasculogenic claudication, neurogenic claudication most often occurs secondary to nerve root compression on exit from the spinal canal. Radicular pain is frequently brought on by simple weight bearing or changes in posture (e.g., rising after prolonged sitting) and relieved by a change in position to relieve the load on the spine (e.g., lumbar flexion, sitting down). These features are in distinct contrast to vasculogenic claudication, which is induced by leg exercise and quickly relieved by rest (resulting in a decrease in muscular metabolic requirement), without a need to change position.[10]
Health Disparities in PAD Symptoms
Significant disparities exist in the presentation and recognition of PAD symptoms across sex and race.
Prevalence: The prevalence of PAD is similar in men and women; after age 55 years, incidence is not substantially different between sexes. Black individuals have approximately 2-fold higher prevalence compared with White individuals; Black men aged ≥80 years have a 59% prevalence compared with 22.6% in non-Hispanic White individuals at similar ages.
Symptoms: Women with PAD have a higher prevalence of atypical leg symptoms and asymptomatic PAD. Black patients with PAD also have a higher prevalence of atypical leg symptoms and asymptomatic PAD compared with White patients.
Implications: PAD may be overlooked in women if clinicians believe women are protected from cardiovascular disease. Higher prevalence of asymptomatic PAD and atypical symptoms in Black patients may lead to underdiagnosis.
Management of Patients With Peripheral Artery Disease (Compilation of 2005 and 2011 ACCF/AHA Guideline Recommendations) : A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines (DO NOT EDIT) [11]
Vascular History and Physical Examination
| Class I |
| "1. Individuals at risk for lower extremity PAD should undergo a vascular review of symptoms to assess walking impairment, claudication, ischemic rest pain, and/or the presence of nonhealing wounds. (Level of Evidence: C)" |
| "2. Individuals at risk for lower extremity PAD should undergo comprehensive pulse examination and inspection of the feet. (Level of Evidence: C)" |
| "3. Individuals over 50 years of age should be asked if they have a family history of a first-order relative with an abdominal aortic aneurysm. (Level of Evidence: C)" |
Clinical Presentation (Asymptomatic)
| Class I |
| "1.A history of walking impairment, claudication, ischemic rest pain, and/or nonhealing wounds is recommended as a required component of a standard review of symptoms for adults 50 years and older who have atherosclerosis risk factors and for adults 70 years and older. (Level of Evidence: C)" |
| "2.Individuals with asymptomatic lower extremity PAD should be identified by examination and/or measurement of the ankle-brachial index (ABI) so that therapeutic interventions known to diminish their increased risk of myocardial infarction (MI), stroke, and death may be offered. (Level of Evidence: B)" |
| "3.Smoking cessation, lipid lowering, and diabetes and hypertension treatment according to current national treatment guidelines are recommended for individuals with asymptomatic lower extremity PAD. (Level of Evidence: B)" |
| "4.Antiplatelet therapy is indicated for individuals with asymptomatic lower extremity PAD to reduce the risk of adverse cardiovascular ischemic events. (Level of Evidence: C)" |
| Class IIa |
| "1.An exercise ABI measurement can be useful to diagnose lower extremity PAD in individuals who are at risk for lower extremity PAD who have a normal ABI (0.91 to 1.30), are without classic claudication symptoms, and have no other clinical evidence of atherosclerosis. (Level of Evidence: C)" |
| "2.A toe-brachial index or pulse volume recording measurement can be useful to diagnose lower extremity PAD in individuals who are at risk for lower extremity PAD who have an ABI greater than 1.30 and no other clinical evidence of atherosclerosis(Level of Evidence: C)" |
| Class IIb |
| "1.Angiotensin-converting enzyme (ACE) inhibition may be considered for individuals with asymptomatic lower extremity PAD for cardiovascular risk reduction.(Level of Evidence: C)" |
Claudication in PAD Patients
| Class I |
| "1. Patients with symptoms of intermittent claudication should undergo a vascular physical examination, including measurement of the ABI. (Level of Evidence: B)" |
| "2. In patients with symptoms of intermittent claudication, the ABI should be measured after exercise if the resting index is normal. (Level of Evidence: B)" |
| "3. Patients with intermittent claudication should have significant functional impairment with a reasonable likelihood of symptomatic improvement and absence of other disease that would comparably limit exercise even if the claudication was improved (e.g., angina, heart failure, chronic respiratory disease, or orthopedic limitations) before undergoing an evaluation for revascularization. (Level of Evidence: C)" |
| "4. Individuals with intermittent claudication who are offered the option of endovascular or surgical therapies should:(a) be provided information regarding supervised claudication exercise therapy and pharmacotherapy;(b) receive comprehensive risk factor modification and antiplatelet therapy;(c) have a significant disability, either being unable to perform normal work or having serious impairment of other activities important to the patient; and (d) have lower extremity PAD lesion anatomy such that the revascularization procedure would have low risk and a high probability of initial and long-term success. (Level of Evidence: C)" |
| Class III |
| "1. Arterial imaging is not indicated for patients with a normal postexercise ABI. This does not apply if other atherosclerotic causes (e.g., entrapment syndromes or isolated internal iliac artery occlusive disease) are suspected. (Level of Evidence: C)" |
References
- ↑ Gerhard-Herman, Gornik, H. L., Barrett, C., Barshes, N. R., Corriere, M. A., Drachman, D. E., Fleisher, L. A., Fowkes, F. G. R., Hamburg, N. M., Kinlay, S., Lookstein, R., Misra, S., Mureebe, L., Olin, J. W., Patel, R. A. G., Regensteiner, J. G., Schanzer, A., Shishehbor, M. H., Stewart, K. J., … Walsh, M. E. (2017). 2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Journal of the American College of Cardiology, 69(11). https://doi.org/10.1016/j.jacc.2016.11.008
- ↑ Leng, G. C., & Fowkes, F. G. (1992). The Edinburgh Claudication Questionnaire: an improved version of the WHO/Rose Questionnaire for use in epidemiological surveys. Journal of Clinical Epidemiology, 45(10), 1101–1109. https://doi.org/10.1016/0895-4356(92)90150-l
- ↑ Boylan, L., Nesbitt, C., Wilson, L., Allen, J., Sims, A., Guri, I., Mawson, P., Oates, C., Stansby, G., & Investigators OBOTN. (2021). Reliability of the Edinburgh Claudication Questionnaire for Identifying Symptomatic PAD in General Practice. Angiology, 72(5). https://doi.org/10.1177/0003319720984882
- ↑ American College of Cardiology & American Heart Association. (2006). ACC/AHA 2005 practice guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): A collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines. Circulation, 113(25), e463–e654. https://pubmed.ncbi.nlm.nih.gov/16549646/
- ↑ Bailey, S. R., Beckman, J. A., Dao, T. D., et al. (2019). ACC/AHA/SCAI/SIR/SVM 2018 appropriate use criteria for peripheral artery intervention. Journal of the American College of Cardiology, 73(2), 214–237. https://doi.org/10.1016/j.jacc.2018.10.002
- ↑ Fitridge R, Chuter V, Mills J, et al. (2023). "The Intersocietal IWGDF, ESVS, SVS Guidelines on Peripheral Artery Disease in People With Diabetes Mellitus and a Foot Ulcer". J Vasc Surg. 78 (5): 1101–1131. doi:10.1016/j.jvs.2023.07.020. PMID 37436988 Check
|pmid=value (help). - ↑ Bonaca MP, Barnes GD, Bauersachs R, et al. (2024). "Antithrombotic Strategies for Patients With Peripheral Artery Disease: JACC Scientific Statement". J Am Coll Cardiol. 84 (10): 936–952. doi:10.1016/j.jacc.2024.06.027. PMID 39197984 Check
|pmid=value (help). - ↑ Wooten C, Hayat M, du Plessis M, et al. (2014). "Anatomical significance in aortoiliac occlusive disease". Clin Anat. 27 (8): 1264–74. doi:10.1002/ca.22444. PMID 25065617.
- ↑ Liao SL, Luthra M, Rogers KM (2009). "Leriche Syndrome". J Am Coll Cardiol. 54 (19): e11. doi:10.1016/j.jacc.2009.06.037. PMID 19874987.
- ↑ Conte MS, Pomposelli FB, Clair DG, et al. (2015). "Society for Vascular Surgery practice guidelines for atherosclerotic occlusive disease of the lower extremities: management of asymptomatic disease and claudication". J Vasc Surg. 61 (3 Suppl): 2S–41S. doi:10.1016/j.jvs.2014.12.009. PMID 25536405.
- ↑ Rooke TW, Hirsch AT, Misra S, Sidawy AN, Beckman JA, Findeiss L; et al. (2013). "Management of patients with peripheral artery disease (compilation of 2005 and 2011 ACCF/AHA Guideline Recommendations): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines". J Am Coll Cardiol. 61 (14): 1555–70. doi:10.1016/j.jacc.2013.01.004. PMC 4492473. PMID 23473760.