Peripheral Arterial Disease

Last Updated: December 9, 2022

Peripheral arterial disease is a condition characterized by a narrowing of the arteries that carry blood away from the heart to other parts of the body. It is usually caused by atherosclerosis. The legs and feet are most commonly affected, resulting in reduced blood flow to these areas.

examine-databaseExamine Database

Peripheral Arterial Disease falls under theCardiovascular Healthcategory.

What is peripheral arterial disease?

Peripheral arterial disease affects approximately 6% of adults globally[1] and is characterized by atherosclerosis (a build-up of fatty plaques in arteries) causing a narrowing or blockage of arteries supplying blood to the limbs, usually the lower limbs.[2][3] Peripheral arterial disease lowers a person’s quality of life (due to pain and poor mobility), increases their risk of requiring a lower limb amputation, and raises their risk of dying from coronary heart disease.[2][3]

What are the main signs and symptoms of peripheral arterial disease?

The main symptom of peripheral arterial disease is lower-leg pain, aching, or cramping that develops during physical activity (e.g., walking) and subsides after stopping. This symptom is called intermittent claudication. One other symptom which suggests more severe disease is lower leg and foot pain when lying down, which improves when the leg hangs down. This symptom is called rest pain. People with peripheral arterial disease may also have cold or numb toes and notice persistent sores or ulcers on their legs.[2][3]

The signs of peripheral arterial disease include clinical tests showing a weak or absent pulse in the feet, muscle atrophy and weakness in the lower leg, poor muscle oxygenation during exercise, and leg pain during a treadmill walking test.[2][3]

How is peripheral arterial disease diagnosed?

To make a diagnosis, people with signs and symptoms of peripheral arterial disease undergo a resting ankle-brachial index (ABI) test. This test uses Doppler ultrasound to compare blood pressure in the ankles with blood pressure in the arms, at rest. In some people, a resting ABI test is followed up with an exercise ABI test during treadmill walking. A person with an abnormal ankle-to-arm blood pressure ratio (e.g., ABI ≤ 0.90) is typically followed up with ultrasound imaging, magnetic resonance angiography, or computed tomographic angiography. These imaging tests visualize the affected arteries to identify the location of narrowing (stenosis) or blockage (occlusion) and to measure the extent to which the narrowing/blockage has progressed. These tests help inform the subsequent therapeutic approach.[2]

What are some of the main medical treatments for peripheral arterial disease?

Treatment of peripheral arterial disease focuses on the “modifiable” risk factors: smoking, physical inactivity, high blood glucose, high blood lipids, and high blood pressure.[2][3][4]

  • Stopping smoking reduces the risk of amputation and heart attack, and prolongs survival.[5]
  • Regular exercise relieves intermittent claudication (calf pain during walking) and improves exercise capacity and quality of life.[6][7]
  • Lipid-lowering drugs lessen the risk of coronary events.[8][9] If the patient has diabetes or hypertension, glucose-lowering and blood pressure-lowering therapies are also recommended.[2][10]

Other drugs are also used to lessen symptoms of intermittent claudication and improve walking distance (e.g., cilostazol[11]) and to help prevent major cardiovascular events (e.g., clopidogrel[12][13]).

Have any supplements been studied for peripheral arterial disease?

Several supplements have been studied in people with peripheral arterial disease. These include alpha-lipoic acid, arginine, carnitine, creatine, fish oil (which contains omega-3 fatty acids), flaxseed, ginkgo biloba, nitrate, resveratrol, etc. For many of these supplements, including creatine, omega-3 fatty acids, and ginkgo biloba, there is no clear benefit.[14][15][16][17][18][19] However, carnitine supplementation lowers intermittent claudication (calf pain during exercise) and increases walking distance in people with peripheral arterial disease.[20] Furthermore, emerging data show that nitrate supplementation can improve limb blood flow, vascular function, and exercise capacity in people with peripheral arterial disease.[21][22][23][24]

How could diet affect peripheral arterial disease?

In some studies, a higher saturated fat intake is associated with a greater risk of peripheral arterial disease.[25] Furthermore, one intervention study found that people randomized to a Mediterranean diet had a lower risk of developing peripheral arterial disease compared to people receiving a control diet.[26][27] But, due to a lack of high-quality randomized controlled trials, the direct effects of specific diets (e.g., a Mediterranean diet) or specific nutrients (e.g., saturated fat) on peripheral arterial disease are unclear and require further investigation.[28] In general, these dietary patterns can also modify the risk of other vascular diseases (e.g., coronary artery disease) that share the same underlying mechanism of disease: atherosclerosis, the narrowing or blockage of arteries due to fatty plaques.[29][30][31]

Are there any other treatments for peripheral arterial disease?

When the main treatments are insufficient to treat the symptoms of peripheral arterial disease, revascularization is also used to restore blood flow to lower limbs.[2][3][4] This typically involves a procedure called balloon angioplasty, which widens blocked or narrowed arteries, consequently relieving intermittent claudication (calf pain during exercise) and improving exercise capacity and quality of life.[32][33]

Emerging treatment options include nitrate drugs (e.g., nitroglycerin), to improve blood flow; autologous stem cell therapy, to increase vascularization; and lower extremity electrical stimulation, to improve functional capacity.[4][34] But these options require further investigation before firm conclusions about their safety and efficacy are possible.

What causes peripheral arterial disease?

The narrowing or blockage of arteries in peripheral arterial disease is caused by a progressive build-up of fatty plaques in the lining of the affected artery.[4] This complex process is called atherosclerosis, and it is influenced by genetics and promoted by lifestyle factors such as smoking, diet, physical inactivity, and excessive weight gain.[4]

Supplements Demystified: Get Our Unbiased, Evidence-Based Guide

Examine Database: Peripheral Arterial Disease
What works and what doesn't?

Unlock the full potential of Examine

Get started

Don't miss out on the latest research

  1. ^Song P, Rudan D, Zhu Y, Fowkes FJI, Rahimi K, Fowkes FGR, Rudan IGlobal, regional, and national prevalence and risk factors for peripheral artery disease in 2015: an updated systematic review and analysis.Lancet Glob Health.(2019-Aug)
  2. ^Gerhard-Herman MD, Gornik HL, Barrett C, Barshes NR, Corriere MA, Drachman DE, Fleisher LA, Fowkes FG, Hamburg NM, Kinlay S, Lookstein R, Misra S, Mureebe L, Olin JW, Patel RA, Regensteiner JG, Schanzer A, Shishehbor MH, Stewart KJ, Treat-Jacobson D, Walsh ME2016 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-Mar-21)
  3. ^Tsao CW, Aday AW, Almarzooq ZI, Alonso A, Beaton AZ, Bittencourt MS, Boehme AK, Buxton AE, Carson AP, Commodore-Mensah Y, Elkind MSV, Evenson KR, Eze-Nliam C, Ferguson JF, Generoso G, Ho JE, Kalani R, Khan SS, Kissela BM, Knutson KL, Levine DA, Lewis TT, Liu J, Loop MS, Ma J, Mussolino ME, Navaneethan SD, Perak AM, Poudel R, Rezk-Hanna M, Roth GA, Schroeder EB, Shah SH, Thacker EL, VanWagner LB, Virani SS, Voecks JH, Wang NY, Yaffe K, Martin SSHeart Disease and Stroke Statistics-2022 Update: A Report From the American Heart Association.Circulation.(2022-Feb-22)
  4. ^Golledge JUpdate on the pathophysiology and medical treatment of peripheral artery disease.Nat Rev Cardiol.(2022-Jul)
  5. ^Armstrong EJ, Wu J, Singh GD, Dawson DL, Pevec WC, Amsterdam EA, Laird JRSmoking cessation is associated with decreased mortality and improved amputation-free survival among patients with symptomatic peripheral artery disease.J Vasc Surg.(2014-Dec)
  6. ^Lane R, Harwood A, Watson L, Leng GCExercise for intermittent claudication.Cochrane Database Syst Rev.(2017-Dec-26)
  7. ^Treat-Jacobson D, McDermott MM, Bronas UG, Campia U, Collins TC, Criqui MH, Gardner AW, Hiatt WR, Regensteiner JG, Rich K,Optimal Exercise Programs for Patients With Peripheral Artery Disease: A Scientific Statement From the American Heart Association.Circulation.(2019-Jan-22)
  8. ^Aung PP, Maxwell HG, Jepson RG, Price JF, Leng GCLipid-lowering for peripheral arterial disease of the lower limb.Cochrane Database Syst Rev.(2007-Oct-17)
  9. ^Sofat S, Chen X, Chowdhury MM, Coughlin PAEffects of Statin Therapy and Dose on Cardiovascular and Limb Outcomes in Peripheral Arterial Disease: A Systematic Review and Meta-analysis.Eur J Vasc Endovasc Surg.(2021-Sep)
  10. ^Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, DePalma SM, Gidding S, Jamerson KA, Jones DW, MacLaughlin EJ, Muntner P, Ovbiagele B, Smith SC Jr, Spencer CC, Stafford RS, Taler SJ, Thomas RJ, Williams KA Sr, Williamson JD, Wright JT Jr2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice GuidelinesHypertension.(2018 Jun)
  11. ^Brown T, Forster RB, Cleanthis M, Mikhailidis DP, Stansby G, Stewart MCilostazol for intermittent claudication.Cochrane Database Syst Rev.(2021-Jun-30)
  12. ^Squizzato A, Bellesini M, Takeda A, Middeldorp S, Donadini MPClopidogrel plus aspirin versus aspirin alone for preventing cardiovascular events.Cochrane Database Syst Rev.(2017-Dec-14)
  13. ^Willems LH, Maas DPMSM, Kramers K, Reijnen MMPJ, Riksen NP, Ten Cate H, van der Vijver-Coppen RJ, de Borst GJ, Mees BME, Zeebregts CJ, Hannink G, Warlé MCAntithrombotic Therapy for Symptomatic Peripheral Arterial Disease: A Systematic Review and Network Meta-Analysis.Drugs.(2022-Aug)
  14. ^Domingues WJR, Ritti-Dias RM, Cucato GG, Wolosker N, Zerati AE, Puech-Leão P, Coelho DB, Nunhes PM, Moliterno AA, Avelar AEffect of Creatine Supplementation on Functional Capacity and Muscle Oxygen Saturation in Patients with Symptomatic Peripheral Arterial Disease: A Pilot Study of a Randomized, Double-Blind Placebo-Controlled Clinical Trial.Nutrients.(2021-Jan-05)
  15. ^Bork CS, Lasota AN, Lundbye-Christensen S, Jakobsen MU, Tjønneland A, Calder PC, Schmidt EB, Overvad KIntake of α-linolenic acid is not consistently associated with a lower risk of peripheral artery disease: results from a Danish cohort study.Br J Nutr.(2019-Jul-14)
  16. ^Enns JE, Yeganeh A, Zarychanski R, Abou-Setta AM, Friesen C, Zahradka P, Taylor CGThe impact of omega-3 polyunsaturated fatty acid supplementation on the incidence of cardiovascular events and complications in peripheral arterial disease: a systematic review and meta-analysis.BMC Cardiovasc Disord.(2014-May-31)
  17. ^Campbell A, Price J, Hiatt WROmega-3 fatty acids for intermittent claudication.Cochrane Database Syst Rev.(2013-Jul-04)
  18. ^Nicolaï SP, Kruidenier LM, Bendermacher BL, Prins MH, Stokmans RA, Broos PP, Teijink JAGinkgo biloba for intermittent claudication.Cochrane Database Syst Rev.(2013-Jun-06)
  19. ^McDermott MM, Leeuwenburgh C, Guralnik JM, Tian L, Sufit R, Zhao L, Criqui MH, Kibbe MR, Stein JH, Lloyd-Jones D, Anton SD, Polonsky TS, Gao Y, de Cabo R, Ferrucci LEffect of Resveratrol on Walking Performance in Older People With Peripheral Artery Disease: The RESTORE Randomized Clinical Trial.JAMA Cardiol.(2017-Aug-01)
  20. ^Kamoen V, Vander Stichele R, Campens L, De Bacquer D, Van Bortel L, de Backer TLPropionyl-L-carnitine for intermittent claudication.Cochrane Database Syst Rev.(2021-Dec-26)
  21. ^Kruse NT, Ueda K, Hughes WE, Casey DPEight weeks of nitrate supplementation improves blood flow and reduces the exaggerated pressor response during forearm exercise in peripheral artery disease.Am J Physiol Heart Circ Physiol.(2018-Jul-01)
  22. ^Bock JM, Treichler DP, Norton SL, Ueda K, Hughes WE, Casey DPInorganic nitrate supplementation enhances functional capacity and lower-limb microvascular reactivity in patients with peripheral artery disease.Nitric Oxide.(2018-Nov-01)
  23. ^Pekas EJ, Wooden TK, Yadav SK, Park SYBody mass-normalized moderate dose of dietary nitrate intake improves endothelial function and walking capacity in patients with peripheral artery disease.Am J Physiol Regul Integr Comp Physiol.(2021-Aug-01)
  24. ^Hughes WE, Treichler DP, Ueda K, Bock JM, Casey DPSodium nitrate supplementation improves blood pressure reactivity in patients with peripheral artery disease.Nutr Metab Cardiovasc Dis.(2022-Mar)
  25. ^Adegbola A, Behrendt CA, Zyriax BC, Windler E, Kreutzburg TThe impact of nutrition on the development and progression of peripheral artery disease: A systematic review.Clin Nutr.(2022-Jan)
  26. ^Ruiz-Canela M, Estruch R, Corella D, Salas-Salvadó J, Martínez-González MAAssociation of Mediterranean diet with peripheral artery disease: the PREDIMED randomized trial.JAMA.(2014)
  27. ^Martínez-González MAProtocol Deviations, Reanalyses, and Corrections to PREDIMED Trial Derivative Study on Peripheral Artery Disease.JAMA.(2018-Dec-04)
  28. ^Wan D, Li V, Banfield L, Azab S, de Souza RJ, Anand SSDiet and Nutrition in Peripheral Artery Disease: A Systematic Review.Can J Cardiol.(2022-May)
  29. ^Lee Hooper, Nicole Martin, Oluseyi F Jimoh, Christian Kirk, Eve Foster, Asmaa S AbdelhamidReduction in saturated fat intake for cardiovascular diseaseCochrane Database Syst Rev.(2020 Aug 21)
  30. ^Karen Rees, Andrea Takeda, Nicole Martin, Leila Ellis, Dilini Wijesekara, Abhinav Vepa, Archik Das, Louise Hartley, Saverio StrangesMediterranean-style diet for the primary and secondary prevention of cardiovascular diseaseCochrane Database Syst Rev.(2019 Mar 13)
  31. ^Rosato V, Temple NJ, La Vecchia C, Castellan G, Tavani A, Guercio VMediterranean diet and cardiovascular disease: a systematic review and meta-analysis of observational studies.Eur J Nutr.(2019-Feb)
  32. ^Vemulapalli S, Dolor RJ, Hasselblad V, Subherwal S, Schmit KM, Heidenfelder BL, Patel MR, Schuyler Jones WComparative Effectiveness of Medical Therapy, Supervised Exercise, and Revascularization for Patients With Intermittent Claudication: A Network Meta-analysis.Clin Cardiol.(2015-Jun)
  33. ^Fakhry F, Fokkenrood HJ, Spronk S, Teijink JA, Rouwet EV, Hunink MGMEndovascular revascularisation versus conservative management for intermittent claudication.Cochrane Database Syst Rev.(2018-Mar-08)
  34. ^Jéhannin P, Craughwell M, Omarjee L, Donnelly A, Jaquinandi V, Mahé G, Le Faucheur AA systematic review of lower extremity electrical stimulation for treatment of walking impairment in peripheral artery disease.Vasc Med.(2020-Aug)
  35. ^Fowkes FG, Rudan D, Rudan I, Aboyans V, Denenberg JO, McDermott MM, Norman PE, Sampson UK, Williams LJ, Mensah GA, Criqui MHComparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysisLancet.(2013 Oct 19)
  36. ^Klarin D, Lynch J, Aragam K, Chaffin M, Assimes TL, Huang J, Lee KM, Shao Q, Huffman JE, Natarajan P, Arya S, Small A, Sun YV, Vujkovic M, Freiberg MS, Wang L, Chen J, Saleheen D, Lee JS, Miller DR, Reaven P, Alba PR, Patterson OV, DuVall SL, Boden WE, Beckman JA, Gaziano JM, Concato J, Rader DJ, Cho K, Chang KM, Wilson PWF, O'Donnell CJ, Kathiresan S, , Tsao PS, Damrauer SMGenome-wide association study of peripheral artery disease in the Million Veteran Program.Nat Med.(2019-Aug)
  37. ^Wassel CL, Loomba R, Ix JH, Allison MA, Denenberg JO, Criqui MHFamily history of peripheral artery disease is associated with prevalence and severity of peripheral artery disease: the San Diego population study.J Am Coll Cardiol.(2011-Sep-20)
  38. ^Wahlgren CM, Magnusson PKGenetic influences on peripheral arterial disease in a twin population.Arterioscler Thromb Vasc Biol.(2011-Mar)
  39. ^Klarin D, Tsao PS, Damrauer SMGenetic Determinants of Peripheral Artery Disease.Circ Res.(2021-Jun-11)
Examine Database References
  1. Intermittent Claudication Symptoms - Castaño G, Más Ferreiro R, Fernández L, Gámez R, Illnait J, Fernández CA long-term study of policosanol in the treatment of intermittent claudicationAngiology.(2001 Feb)
  2. Intermittent Claudication Symptoms - Wilson AM, Harada R, Nair N, Balasubramanian N, Cooke JPL-arginine supplementation in peripheral arterial disease: no benefit and possible harmCirculation.(2007 Jul 10)
  3. Nitric Oxide - Jabłecka A, Bogdański P, Balcer N, Cieślewicz A, Skołuda A, Musialik KThe effect of oral L-arginine supplementation on fasting glucose, HbA1c, nitric oxide and total antioxidant status in diabetic patients with atherosclerotic peripheral arterial disease of lower extremitiesEur Rev Med Pharmacol Sci.(2012 Mar)
  4. Intermittent Claudication Symptoms - William R Hiatt, Mark A Creager, Antonino Amato, Eric P BrassEffect of propionyl-L-carnitine on a background of monitored exercise in patients with claudication secondary to peripheral artery diseaseJ Cardiopulm Rehabil Prev.(Mar-Apr 2011)
  5. Walking Ability - G Brevetti, S Perna, C Sabbà, A Rossini, V Scotto di Uccio, E Berardi, L GodiSuperiority of L-propionylcarnitine vs L-carnitine in improving walking capacity in patients with peripheral vascular disease: an acute, intravenous, double-blind, cross-over studyEur Heart J.(1992 Feb)
  6. Walking Ability - G A Barker, S Green, C D Askew, A A Green, P J WalkerEffect of propionyl-L-carnitine on exercise performance in peripheral arterial diseaseMed Sci Sports Exerc.(2001 Sep)
  7. Walking Ability - G Brevetti, M Chiariello, G Ferulano, A Policicchio, E Nevola, A Rossini, T Attisano, G Ambrosio, N Siliprandi, C AngeliniIncreases in walking distance in patients with peripheral vascular disease treated with L-carnitine: a double-blind, cross-over studyCirculation.(1988 Apr)
  8. Blood Flow - C Corsi, M Pollastri, E Marrapodi, D Leanza, S Giordano, S D'IddioL-propionylcarnitine effect on postexercise and postischemic hyperemia in patients affected by peripheral vascular diseaseAngiology.(1995 Aug)
  9. Intermittent Claudication Symptoms - Bauer U6-Month double-blind randomised clinical trial of Ginkgo biloba extract versus placebo in two parallel groups in patients suffering from peripheral arterial insufficiencyArzneimittelforschung.(1984)
  10. Intermittent Claudication Symptoms - Gardner CD, Taylor-Piliae RE, Kiazand A, Nicholus J, Rigby AJ, Farquhar JWEffect of Ginkgo biloba (EGb 761) on treadmill walking time among adults with peripheral artery disease: a randomized clinical trialJ Cardiopulm Rehabil Prev.(2008 Jul-Aug)
  11. Intermittent Claudication Symptoms - Mouren X, Caillard P, Schwartz FStudy of the antiischemic action of EGb 761 in the treatment of peripheral arterial occlusive disease by TcPo2 determinationAngiology.(1994 Jun)
  12. Intermittent Claudication Symptoms - Vincent HK, Bourguignon CM, Vincent KR, Taylor AGEffects of alpha-lipoic acid supplementation in peripheral arterial disease: a pilot studyJ Altern Complement Med.(2007 Jun)
  13. Peripheral Vascular Disease Symptoms - Kiesewetter H, Jung F, Jung EM, Blume J, Mrowietz C, Birk A, Koscielny J, Wenzel EEffects of garlic coated tablets in peripheral arterial occlusive diseaseClin Investig.(1993 May)
  14. Peripheral Vascular Disease Symptoms - Hammer A, Koppensteiner R, Steiner S, Niessner A, Goliasch G, Gschwandtner M, Hoke MDark chocolate and vascular function in patients with peripheral artery disease: a randomized, controlled cross-over trialClin Hemorheol Microcirc.(2015)
  15. Peripheral Vascular Disease Symptoms - Loffredo L, Perri L, Catasca E, Pignatelli P, Brancorsini M, Nocella C, De Falco E, Bartimoccia S, Frati G, Carnevale R, Violi FDark chocolate acutely improves walking autonomy in patients with peripheral artery diseaseJ Am Heart Assoc.(2014 Jul 2)
  16. C-Reactive Protein (CRP) - Mackay I, Ford I, Thies F, Fielding S, Bachoo P, Brittenden JEffect of Omega-3 fatty acid supplementation on markers of platelet and endothelial function in patients with peripheral arterial diseaseAtherosclerosis.(2012 Jan 13)
  17. Endothelial Function - Mohammadipoor N, Shafiee F, Rostami A, Kahrizi MS, Soleimanpour H, Ghodsi M, Ansari MJ, Bokov DO, Jannat B, Mosharkesh E, Pour Abbasi MSResveratrol supplementation efficiently improves endothelial health: A systematic review and meta-analysis of randomized controlled trials.Phytother Res.(2022-Sep)