Intermittent claudication (IC) typically refers to lower extremity skeletal muscle pain that occurs during exercise. IC presents when there is insufficient oxygen delivery to meet the metabolic requirements of the skeletal muscles. IC is a common manifestation of peripheral arterial disease (PAD), which includes atherosclerotic stenosis of arteries in the extremities. IC is commonly localized to the thigh, hip, buttock and calf muscles. Pain within these muscle groups is reproducibly induced by walking and relieved with rest. The severity of pain can sometimes correlate with the degree of stenosis or blockage in arteries supplying the lower extremities.[1][2][3]
The key feature of IC is that the muscle discomfort is reproducible. The pain usually comes on during physical activity and subsides after a period of rest. The key reason for the pain is inadequate blood flow. IC is a very common problem seen in smokers and diabetics.
The risk factors for developing IC are similar to those for developing atherosclerosis. Modifiable risk factors include smoking, hypertension, dyslipidemias, obesity, metabolic syndrome, and diabetes mellitus. Non-modifiable risk factors include age, male gender, family history, and congenital predisposition. Investigational risk factors include alcohol, radiation, C-Reactive Protein, infection, homocysteinemia, lipoprotein(a), reduced adiponectin, and fibrinogen.[4][5]
Besides smoking, poor renal function is also deemed a high-risk factor for the development of IC.
In the general population over age 60 IC is present in 5% of men and 2.5% of women. Of all patients with PAD, between 10-35% will have a presentation of “classic” IC. Certain patient groups have a higher incidence of PAD; these include: age greater than 70, smokers and diabetics between ages 50-69, and those with other atherosclerotic cardiovascular diseases.
IC occurs due to atherosclerosis-mediated narrowing of lower extremity vessels. Oxidative injury to the inner layer of endothelial cells is the nidus of atherogenesis. The subsequent dysfunction of endothelial cells promotes localized deposition of oxidized-LDL and synthesis of pro-inflammatory factors. This creates a fibro-inflammatory plaque that propagates as macrophages are recruited and become resident foam cells as they phagocytize the oxidized-LDL. The foam cells form a classic histologic feature called a “fatty-streak”. As the plaque enlarges and matures, surrounding vascular smooth muscles migrate into it, and collagen deposition forms a fibrous cap. The most common location of plaque formation in PAD is in the superficial femoral artery, which may lead to IC symptoms in the calf. Other locations include the aortoiliac bifurcation, producing hip and buttock pain, and the common femoral artery, which can yield thigh or calf claudication.[6]
The resting blood flow in these individuals is similar to healthy adults but during exercise or physical activity, the blood cannot flow through the areas of obstruction. At the same time, these individuals take a long time to recover from physical activity compared to healthy adults.
The typical presentation of IC is a patient with lower extremity pain during ambulation that is relieved with rest. The progression of symptoms is gradual. The pain may be localized to the buttocks or the lower leg, depending on the site of occlusion. Patients with aortoiliac disease frequently develop buttock pain.
Physical examination of these patients may show evidence of arterial insufficiency. The affected limb may feel cool and have diminished pulses. The physical examination should include an assessment of femoral, popliteal, dorsalis pedis, and posterior tibial artery pulses. The patient’s presentation should be carefully distinguished from other causes of leg pain like neurogenic pseudoclaudication (spinal stenosis), musculoskeletal pain, and venous claudication associated with leg swelling and varicosities. In general, the presence of strong pedal pulses argues against a diagnosis of IC.
If pulses are not palpable, one may have to use a handheld Doppler device. In general, in healthy people, the blood pressure in the arms and ankle should be about the same. In fact, ankle pressure is slightly higher in most people. The Ankle-Brachial index should be measured in all individuals. Patients with an ABI of less than 0.9 may have some degree of vascular disease.
In addition to a full cardiac and respiratory history and physical exam, certain non-invasive and invasive tests can be performed based on the severity of symptoms. All patients should have a baseline lipid profile, Doppler waveform pulse assessment and Ankle-Brachial Indices (ABI). An ABI is a ratio of blood pressure at the ankle compared to the arm. An ABI between 0.9-1.3 is normal. Claudication is common in patients with an ABI between 0.4 and 0.9. ABI less and 0.4 suggests more severe PAD, while an ABI >1.3 is associated with non-compressible calcified arteries. In patients with calcified arteries, commonly diabetics, a Toe-Brachial pressure index (TBI) can be used. The TBI in a healthy patient should be 0.70-0.80. If a symptomatic patient has a normal ABI or TBI, standardized exercise testing can be helpful.
In normal patients, the ABI will increase during exercise. In patients with post-exercise ABI drop of >20%, diagnostic imaging and referral to a vascular specialist are warranted. There are three major classification systems for patients with PAD: Wound/Ischemia/Foot Infection (Wifi), Rutherford, and Fontaine. The older Rutherford and Fontaine systems incorporate intermittent claudication as part of their classification.
Common imaging modalities include non-invasive duplex vascular ultrasound, minimally invasive CTA and MRA, and formal peripheral angiography. Imagining modalities elucidate the location of the diseased vasculature. Aortoiliac disease is referred to as inflow disease, and typically produces symptoms in the thigh or gluteal musculature. Meanwhile, disease below the inguinal ligament commonly produces claudication affecting the calf muscles. [7][8]
The guiding principle of treatment for IC is that few patients, around 1-2%, with claudication ever progress to limb threatening ischemia. Under this pretense, initial aggressive treatment strategies are discouraged. Most patient with IC can be treated with medical management.
Medical management includes smoking cessation, antiplatelet agents, statin therapy, blood pressure modification, glucose control, structured walking programs, and cilostazol. Structured walking programs improve pain-free walking distance better than pharmacologic therapy alone. It is important to note that continued smoking with walking therapy restricts improvement in these patients. A three-month trial of smoking cessation, ambulation and cilostazol is typically prescribed. Headaches are the most common side-effect of cilostazol and may warrant a dose-reduction. Patients undergoing medical management should have frequent follow-ups to assess their symptom relief. Most patients are instructed to walk at least three ten-minute walks daily.
Any patient with intermittent claudication or PAD should also be evaluated for coexisting cardiac disease. If symptoms are worsening despite medical treatment, or if symptoms are considered disabling or lifestyle-limiting, intervention may be considered. Other considerations for invasive procedures may include: atherosclerotic lesion characteristics and patient prognosis. Intervention may initially involve minimally-invasive endovascular angioplasty, stenting or atherectomy.
Percutaneous techniques are typically performed via the femoral artery with the insertion of a sheath with wires and catheters to the diseased region. Lesions that are multifocal, long or heavily calcified may not be amenable to endovascular repair. In these cases, intervention may ultimately require endarterectomy or a conduit bypass. The conduit can either be and autogenous vein or a prosthetic material. In 2007 the Society for Vascular Surgery developed the Trans-Atlantic Inter-Society Consensus (TASC II) guidelines that can aid physicians in determining whether endovascular or open surgery should be pursued in a patient. The classification identifies lesions as A, B, C or D based on location, number, length, and severity of the stenosis. The complications of any surgical intervention should also be considered -- these include vessel or graft conduit thrombosis, in-stent stenosis or fracture, and infection. [3][9][10]
Current Guidelines on PVD
The prognosis of IC depends on many factors. For those who continue to smoke, have uncontrolled hypertension or elevated blood glucose, the condition can progress leading to ischemia, necrosis and eventually amputation of the limb. Besides smoking, two factors that negatively affect prognosis include diabetes and advanced age. Overall, the survival of patients with IC is less than that of aged-matched controls. The key reason for the shortened life expectancy is the presence of coronary artery disease. About 5-30% of individuals are dead at 10 years, depending on the severity of the vascular disease.
Vascular surgery
Interventional radiologist
The treatment of intermittent claudication is surrounded with controversy. The past belief that exercise therapy alone could improve the disease and symptoms is now known to have many shortcomings. The older studies were never standardized, did not use adequate measures of outcomes and were heterogeneous- meaning that the patient population was not controlled and the type of exercise was not controlled. While the debate rages, experts agree that prevention of claudication is perhaps the best way to manage the disease. The pharmacist and nurse are in the ideal position to educate the patient on the risks of smoking and lack of exercise. Patients with intermittent claudication must be told to eat a healthy diet, control the blood sugars and hypertension, lower the levels of cholesterol and glucose and participate in an exercise program. There is ample evidence showing that undertaking these measures improves quality of life and reduces the burden of many medical disorders.[11][12][13](Level II)
Outcomes
The latest data suggest that in patients with intermittent claudication, endovascular surgery, open surgery, and exercise therapy are superior to medical management in terms of walking distance and symptom relief. (Level V) However, there are no good long-term studies to determine which of the procedures is more effective. The data on exercise therapy alone are conflicting and only of short-term duration. What is also not known is how many additional endovascular procedures will be required in the future to keep the patient symptom free. Whether any of these treatments can improve claudication over the long term still remains to be seen. [14][15][16]
[1] | Abaraogu U,Ezenwankwo E,Dall P,Tew G,Stuart W,Brittenden J,Seenan C, Barriers and enablers to walking in individuals with intermittent claudication: A systematic review to conceptualize a relevant and patient-centered program. PloS one. 2018 [PubMed PMID: 30048501] |
[2] | Golledge J,Maarij K,Moxon JV,Beard JD,Girold S,Wrang H,Morris DR, Systematic Review and Meta-analysis of Clinical Trials Examining the Benefit of Exercise Programmes Using Nordic Walking in Patients With Peripheral Artery Disease. European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery. 2018 Jul 12 [PubMed PMID: 30017508] |
[3] | Skórkowska-Telichowska K,Kropielnicka K,Bulińska K,Pilch U,Woźniewski M,Szuba A,Jasiński R, Insufficient modification of atherosclerosis risk factors in PAD patients. Advances in clinical and experimental medicine : official organ Wroclaw Medical University. 2018 Jun [PubMed PMID: 30059197] |
[4] | Weiss NS,McClelland R,Criqui MH,Wassel CL,Kronmal R, Incidence and predictors of clinical peripheral artery disease in asymptomatic persons with a low ankle-brachial index. Journal of medical screening. 2018 Jan 1 [PubMed PMID: 29720042] |
[5] | Falconer D,Papageorgiou N,Salem K,Lim WY,Katsargyris A,Avgerinos E,Tousoulis D, Nitric oxide donors for peripheral artery disease. Current opinion in pharmacology. 2018 Apr [PubMed PMID: 29587164] |
[6] | McDermott MM,Carroll T,Carr J,Yuan C,Ferrucci L,Guralnik JM,Kibbe M,Criqui MH,Tian L,Polonsky T,Zhao L,Gao Y,Hippe DS,Xu D,McCarthy W,Kramer CM, Femoral artery plaque characteristics, lower extremity collaterals, and mobility loss in peripheral artery disease. Vascular medicine (London, England). 2017 Dec [PubMed PMID: 28965473] |
[7] | Fabiani I,Calogero E,Pugliese NR,Di Stefano R,Nicastro I,Buttitta F,Nuti M,Violo C,Giannini D,Morgantini A,Conte L,Barletta V,Berchiolli R,Adami D,Ferrari M,Di Bello V, Critical Limb Ischemia: A Practical Up-To-Date Review. Angiology. 2018 Jul [PubMed PMID: 29161885] |
[8] | Ahmed O,Hanley M,Bennett SJ,Chandra A,Desjardins B,Gage KL,Gerhard-Herman MD,Ginsburg M,Gornik HL,Oliva IB,Steigner ML,Strax R,Verma N,Rybicki FJ,Dill KE, ACR Appropriateness Criteria{sup}®{/sup} Vascular Claudication-Assessment for Revascularization. Journal of the American College of Radiology : JACR. 2017 May [PubMed PMID: 28473094] |
[9] | Garrigues D,Ferrari B,Petrissans Ferrando N,Guiraut T, [Vascular rehabilitation in lower-extremity artery diseasein 2018]. Presse medicale (Paris, France : 1983). 2018 Jan [PubMed PMID: 29395558] |
[10] | Espinola-Klein C, [ESC guidelines 2017 on peripheral arterial diseases : Summary of the most important recommendations and innovations]. Herz. 2017 Dec [PubMed PMID: 29143147] |
[11] | Walsworth MK,de Bie R,Figoni SF,O'Connell JB, Peripheral Artery Disease: What You Need to Know. The Journal of orthopaedic and sports physical therapy. 2017 Dec [PubMed PMID: 28992768] |
[12] | Morère PH, [Intermittent claudication and critical limb ischemia : from diagnosis to management]. Revue medicale suisse. 2017 Mar 1 [PubMed PMID: 28714619] |
[13] | Fokkenrood HJ,Lauret GJ,Scheltinga MR,Spreeuwenberg C,de Bie RA,Teijink JA, Multidisciplinary treatment for peripheral arterial occlusive disease and the role of eHealth and mHealth. Journal of multidisciplinary healthcare. 2012 [PubMed PMID: 23093906] |
[14] | Spiliopoulos S,Moulakakis K,Palialexis K,Konstantos C,Reppas L,Kakisis I,Lazaris A,Geroulakos G,Brountzos E, Long-term Outcomes of Percutaneous Stenting of Aortic Endograft Limb Occlusion. Annals of vascular surgery. 2018 Aug 6 [PubMed PMID: 30092436] |
[15] | Hageman D,Fokkenrood HJ,Gommans LN,van den Houten MM,Teijink JA, Supervised exercise therapy versus home-based exercise therapy versus walking advice for intermittent claudication. The Cochrane database of systematic reviews. 2018 Apr 6 [PubMed PMID: 29627967] |
[16] | Kalbaugh CA,Gonzalez NJ,Luckett DJ,Fine J,Brothers TE,Farber MA,Beck AW,Hallett JW Jr,Marston WA,Vallabhaneni R, The impact of current smoking on outcomes after infrainguinal bypass for claudication. Journal of vascular surgery. 2018 Aug [PubMed PMID: 29506947] |