Review Article

Peripheral Arterial Disease: Current Perspectives and New Trends in Management

Authors: Farhan Aslam MD, Attiya Haque MD, Joanne Foody MD, L Veronica Lee MD

Abstract

Abstract:Peripheral arterial disease (PAD) is defined as an arterial brachial index (ABI) of ≤0.90 in the lower extremities and results from a narrowing of the arteries as a result of progressive atherosclerosis. PAD affects 12–20% of Americans aged 65 years or older; however, most are asymptomatic and many do not seek treatment. Improved awareness and education in both the general population and among health care providers about these modifiable risk factors has the potential to improve general health and decrease morbidity and mortality secondary to atherosclerotic vascular disease.

This content is limited to qualifying members.

Existing members, please login first

If you have an existing account please login now to access this article or view purchase options.

Purchase only this article ($25)

Create a free account, then purchase this article to download or access it online for 24 hours.

Purchase an SMJ online subscription ($75)

Create a free account, then purchase a subscription to get complete access to all articles for a full year.

Purchase a membership plan (fees vary)

Premium members can access all articles plus recieve many more benefits. View all membership plans and benefit packages.

References

References1. Norgren L, Hiatt WR, Dormandy JA, et al; TASC II Working Group. Inter-society consensus for the management of peripheral arterial disease (TASC II). J Vasc Surg 2007;45(Suppl S):S5–S67.NorgrenL]]HiattWR]]DormandyJA&etal;TASC II Working GroupInter-society consensus for the management of peripheral arterial disease (TASC II).J Vasc Surg200745S5-S672. Becker GJ, McClenny TE, Kovacs ME, et al. The importance of increasing public and physician awareness on peripheral artery disease. J Vasc Interv Radiol 2002;13:7–11.BeckerGJ]]McClennyTE]]KovacsME&etal;The importance of increasing public and physician awareness on peripheral artery disease.J Vasc Interv Radiol2002137-113. Murabito JM, D’Agostino RB, Silbershatz H, et al. Intermittent claudication. A risk profile from the Framingham heart study Circulation 1997;96:44–49.MurabitoJM]]D’AgostinoRB]]SilbershatzH&etal;Intermittent claudication. A risk profile from the Framingham heart studyCirculation19979644-494. Reeder BA, Liu L, Horlick L. Sociodemographic variation in the prevalence of cardiovascular disease. Can J Cardiol 1996;12:271–275.ReederBA]]LiuL]]HorlickLSociodemographic variation in the prevalence of cardiovascular disease.Can J Cardiol199612271-2755. Criqui MH, Fronek A, Barrett-Connor E, et al. The prevalence of peripheral arterial disease in a defined population. Circulation 1985;71:510–517.CriquiMH]]FronekA]]Barrett-ConnorE&etal;The prevalence of peripheral arterial disease in a defined population.Circulation198571510-5176. Selvin E, Erlinger TP. Prevalence of and risk factors for peripheral arterial disease in the United States: results from the National Health and Nutrition Examination Survey, 1999–2000. Circulation 2004;110:738–742.SelvinE]]ErlingerTPPrevalence of and risk factors for peripheral arterial disease in the United States: results from the National Health and Nutrition Examination Survey, 1999–2000.Circulation2004110738-7427. Colins TC, Peterson NJ, Suarez-Almazor M, et al. The prevalence of peripheral arterial disease in a racially diverse population. Arch Intern Med 2003;163:1469–1474.ColinsTC]]PetersonNJ]]Suarez-AlmazorM&etal;The prevalence of peripheral arterial disease in a racially diverse population.Arch Intern Med20031631469-14748. Gerhard GT, Malinow MR, DeLoughery TG, et al. Higher total homocysteine concentration and lower folate concentrations in premenopausal black women than in premenopausal white women. Am J Clin Nutr 1999;70:252–260.GerhardGT]]MalinowMR]]DeLougheryTG&etal;Higher total homocysteine concentration and lower folate concentrations in premenopausal black women than in premenopausal white women.Am J Clin Nutr199970252-2609. Folsom AR, Wu KK, Conlan MG, et al. Distributions of hemostatic variables in black and whites: population reference values from the Atherosclerosis Risk in Communities (ARIC) study. Ethn Dis 1992;2:35–46.FolsomAR]]WuKK]]ConlanMG&etal;Distributions of hemostatic variables in black and whites: population reference values from the Atherosclerosis Risk in Communities (ARIC) study.Ethn Dis1992235-4610. Conlan MG, Folsom AR, Finch A, et al. Associations of Factor VIII and von Willebrand factor with age, race, sex and risk factors for atherosclerosis: the Atherosclerosis Risk in Communities (ARIC) study. Thromb Haemost. 1993;70:380–385.ConlanMG]]FolsomAR]]FinchA&etal;Associations of Factor VIII and von Willebrand factor with age, race, sex and risk factors for atherosclerosis: the Atherosclerosis Risk in Communities (ARIC) study.Thromb Haemost199370380-38511. Fowkes FG, Lee AJ, Hou CM, et al. Methylene tetrahydrofolate reductase (MTHFR) and nitric oxide synthase (ecNOS) genes and risk of peripheral arterial disease and coronary heart disease: Edinburgh artery study. Atherosclerosis 2000;150:179–185.FowkesFG]]LeeAJ]]HouCM&etal;Methylene tetrahydrofolate reductase (MTHFR) and nitric oxide synthase (ecNOS) genes and risk of peripheral arterial disease and coronary heart disease: Edinburgh artery study.Atherosclerosis2000150179-18512. Gordon T, Kannel WB. Predisposition to atherosclerosis in the head, heart, and legs: the Framingham study JAMA 1972;221:661–666.GordonT]]KannelWBPredisposition to atherosclerosis in the head, heart, and legs: the Framingham studyJAMA1972221661-66613. Lu JT, Creager MA. The relationship of cigarette smoking to peripheral arterial disease. Cardiovasc Med 2004;5:189–193.LuJT]]CreagerMAThe relationship of cigarette smoking to peripheral arterial disease.Cardiovasc Med20045189-19314. Beckman J, Creager MA. Management of Peripheral Arterial Disease. London, ReMEDICA publishing, 2000,pp 19–42.BeckmanJ]]CreagerMAManagement of Peripheral Arterial Disease.LondonReMEDICA publishing200019-4215. Beckman JA, Creager MA, Libby P. Diabetes and atherosclerosis: epedimiology, pathophysiology, and management. JAMA 2002 287:2570–2581.BeckmanJA]]CreagerMA]]LibbyPDiabetes and atherosclerosis: epedimiology, pathophysiology, and management.JAMA20022872570-258116. Murabito JM, D’ Agostino RB, Silbershatz H, et al. Intermittent claudication: a risk profile from the Framingham heart study. Circulation 1997;96:44–49.MurabitoJM]]D’ AgostinoRB]]SilbershatzH&etal;Intermittent claudication: a risk profile from the Framingham heart study.Circulation19979644-4917. Murabito JM, Evans JC, Nieto K, et al. Prevalence and clinical correlates of peripheral arterial disease in the Framingham offspring study. Am Heart J 2002;143:961–968.MurabitoJM]]EvansJC]]NietoK&etal;Prevalence and clinical correlates of peripheral arterial disease in the Framingham offspring study.Am Heart J2002143961-96818. Criqui MH, Denenberg JO, Langer RD, et al. The epidemiology of peripheral artery disease: Importance of identifying the population at risk. Vasc Med 1997;2:221–225.CriquiMH]]DenenbergJO]]LangerRD&etal;The epidemiology of peripheral artery disease: Importance of identifying the population at risk.Vasc Med19972221-22519. Greenhalgh RM, Rosengarten DS, Mervart I, et al. Serum lipids and lipoproteins in the peripheral vascular disease. Lancet 1971;2:947–950.GreenhalghRM]]RosengartenDS]]MervartI&etal;Serum lipids and lipoproteins in the peripheral vascular disease.Lancet19712947-95020. Bradby GV, Valente AJ, Walton KW. Serum high-density lipoproteins in peripheral vascular disease. Lancet 1978;2:1271–1274.BradbyGV]]ValenteAJ]]WaltonKWSerum high-density lipoproteins in peripheral vascular disease.Lancet197821271-127421. Smith FB, Lee AJ, Hau CM, et al. Plasma fibrinogen, hemostatic factors and prediction of peripheral arterial disease in Edinburgh artery study. Blood Coagul Fibrinolysis 2000;11:43–50.SmithFB]]LeeAJ]]HauCM&etal;Plasma fibrinogen, hemostatic factors and prediction of peripheral arterial disease in Edinburgh artery study.Blood Coagul Fibrinolysis20001143-5022. Vidula H, Tian L, Liu K, et al. Biomarkers of inflammation and thrombosis as predictors of near-term mortality in patients with peripheral arterial disease: a cohort study. Ann Intern Med 2008;148:85–93.VidulaH]]TianL]]LiuK&etal;Biomarkers of inflammation and thrombosis as predictors of near-term mortality in patients with peripheral arterial disease: a cohort study.Ann Intern Med200814885-9323. Boushey CJ, Beresford SA, Omenn GS, et al. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA 1995;274:1049–1057.BousheyCJ]]BeresfordSA]]OmennGS&etal;A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes.JAMA19952741049-105724. Hajjar KA. Homocysteine-induced modulation of tissue plasminogen activator binding to its endothelial cell membrane receptor. J Clin Invest 1993;91:2873–2879.HajjarKAHomocysteine-induced modulation of tissue plasminogen activator binding to its endothelial cell membrane receptor.J Clin Invest1993912873-287925. McDermott MM, Greenland P, Liu K, et al. Leg symptoms in peripheral arterial disease: associated clinical characteristics and functional impairment. JAMA 2001;286:1599–1606.McDermottMM]]GreenlandP]]LiuK&etal;Leg symptoms in peripheral arterial disease: associated clinical characteristics and functional impairment.JAMA20012861599-160626. Hirsch AT, Haskal ZJ, Hertzer NR, et al. 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 (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. Circulation 2006;113:e463–e654.HirschAT]]HaskalZJ]]HertzerNR&etal;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 (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease): endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation.Circulation2006113e463-e65427. Mcgee SR, Boyko EJ. Physical examination and chronic lower-extremity ischemia: a critical review. Arch Intern Med 1998;158:1357–1364.McgeeSR]]BoykoEJPhysical examination and chronic lower-extremity ischemia: a critical review.Arch Intern Med19981581357-136428. Criqui MH, Fronek A, Klauber MR, et al. The sensitivity, specificity, and predictive value of traditional clinical evaluation of peripheral arterial disease: results from noninvasive testing in a defined population. Circulation 1985;71:516–522.CriquiMH]]FronekA]]KlauberMR&etal;The sensitivity, specificity, and predictive value of traditional clinical evaluation of peripheral arterial disease: results from noninvasive testing in a defined population.Circulation198571516-52229. Ouriel K. Peripheral arterial disease. Lancet 2001;358:1257–1264.OurielKPeripheral arterial disease.Lancet20013581257-126430. Belch JJ, Topol EJ, Agnelli G, et al. Critical issues in peripheral arterial disease detection and management: a call to action. Arch Intern Med 2003;163:884–892.BelchJJ]]TopolEJ]]AgnelliG&etal;Critical issues in peripheral arterial disease detection and management: a call to action.Arch Intern Med2003163884-89231. Vogt MT, Cauley JA, Newman AB, et al. Decreased ankle/arm blood pressure index and mortality in elderly women. JAMA 1993;270:465–469.VogtMT]]CauleyJA]]NewmanAB&etal;Decreased ankle/arm blood pressure index and mortality in elderly women.JAMA1993270465-46932. Resnick HE, Lindsay RS, McDermott MM, et al. Relationship of high and low ankle brachial index to all-cause and cardiovascular disease mortality: the Strong heart study. Circulation 2004;109:733–739.ResnickHE]]LindsayRS]]McDermottMM&etal;Relationship of high and low ankle brachial index to all-cause and cardiovascular disease mortality: the Strong heart study.Circulation2004109733-73933. Darling RC, Raines JK, Brener BJ, et al. Quantitative segmental pulse volume recorder: a clinical tool. Surgery 1972;72:873–877.DarlingRC]]RainesJK]]BrenerBJ&etal;Quantitative segmental pulse volume recorder: a clinical tool.Surgery197272873-87734. Ho KY, de Hann MW, Kessels AG, et al. Peripheral vascular tree stenoses:detection with substracted and nonsubstracted MR angiography. Radiology 1998;206:673–681.HoKY]]de HannMW]]KesselsAG&etal;Peripheral vascular tree stenoses:detection with substracted and nonsubstracted MR angiography.Radiology1998206673-68135. Marckmann P, Skov L, Rossen K, et al. Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance imaging. J Am Soc Nephrol 17:2359–2362.MarckmannP]]SkovL]]RossenK&etal;Nephrogenic systemic fibrosis: suspected causative role of gadodiamide used for contrast-enhanced magnetic resonance imaging.J Am Soc Nephrol&NA;172359-236236. Grobner T. Gadolinium, a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis? Nephrol Dial Transplant 2006;21:1104–1108.GrobnerTGadolinium, a specific trigger for the development of nephrogenic fibrosing dermopathy and nephrogenic systemic fibrosis?Nephrol Dial Transplant2006211104-110837. Quick CR, Cotton LT. The measured effect of stopping smoking on intermittent claudication. Br J Surg 1982;(69 suppl): S24–S26.QuickCR]]CottonLTThe measured effect of stopping smoking on intermittent claudication.Br J Surg1982&NA;S24-S2638. Jonason T, Bergström R. Cessation of smoking in patients with intermittent claudication. Effects on the risk of peripheral vascular complications, myocardial infarction and mortality. Acta Med Scand 1987;221:253–260.JonasonT]]BergströmRCessation of smoking in patients with intermittent claudication. Effects on the risk of peripheral vascular complications, myocardial infarction and mortality.Acta Med Scand1987221253-26039. Norgren L, Hiatt WR, Dormandy JA, et al. Inter-society consensus for the management of peripheral arterial disease (TASC II). J Vasc Surg 2007;(45 suppl S): S5–S67.NorgrenL]]HiattWR]]DormandyJA&etal;Inter-society consensus for the management of peripheral arterial disease (TASC II).J Vasc Surg2007&NA;S5-S6740. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993;329:977–986.&NA;The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group.N Engl J Med1993329977-98641. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) group. Lancet 1998;352:837–853.&NA;Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) group.Lancet1998352837-85342. Action to Control Cardiovascular Risk in Diabetes Study Group; Gerstein HC, Miller ME, Byington RP, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008;358:2545–2559.43. ADVANCE Collaborative Group; Patel M, MacMahon S, Chalmers J, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008;358:2560–2572.ADVANCE Collaborative GroupPatelM]]MacMahonS]]ChalmersJ&etal;Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.N Engl J Med20083582560-257244. Radack K, Deck C. Beta-adrenergic blocker therapy does not worsen intermittent claudication in subjects with peripheral arterial disease. A meta-analysis of randomized controlled trials. Arch Intern Med 1991;151:1769–1776.RadackK]]DeckCBeta-adrenergic blocker therapy does not worsen intermittent claudication in subjects with peripheral arterial disease. A meta-analysis of randomized controlled trials.Arch Intern Med19911511769-177645. Thadani U, Whitsett TL. Beta-adrenergic blockers and intermittent claudication. Time for reappraisal. Arch Intern Med 1991;151:1705–1707.ThadaniU]]WhitsettTLBeta-adrenergic blockers and intermittent claudication. Time for reappraisal.Arch Intern Med19911511705-170746. Leng GC, Fowler B, Ernst E. Exercise for intermittent claudication. Cochrane Database Syst Rev 2000;2:CD000990.LengGC]]FowlerB]]ErnstEExercise for intermittent claudication.Cochrane Database Syst Rev20002CD00099047. Garg PK, Tian L, Criqui MH, et al. Physical activity during daily life and mortality in patients with peripheral arterial disease. Circulation 2006;114:242–248.GargPK]]TianL]]CriquiMH&etal;Physical activity during daily life and mortality in patients with peripheral arterial disease.Circulation2006114242-24848. Wilhite DB, Comerota AJ, Schmieder FA, et al. Managing PAD with multiple platelet inhibitors: the effect of combination therapy on bleeding time. J Vasc Surg 2003;38:710–713.WilhiteDB]]ComerotaAJ]]SchmiederFA&etal;Managing PAD with multiple platelet inhibitors: the effect of combination therapy on bleeding time.J Vasc Surg200338710-71349. Goldhaber SZ, Manson JE, Stampfer MJ, et al. Low-dose aspirin and subsequent peripheral arterial surgery in the Physicians’ Health Study. Lancet 1992;340:143–145.GoldhaberSZ]]MansonJE]]StampferMJ&etal;Low-dose aspirin and subsequent peripheral arterial surgery in the Physicians’ Health Study.Lancet1992340143-14550. A randomized, blinded, trial of clopidogrel versus aspirin in patients at risk of ischemic events (CAPRIE). CAPRIE Steering Committee. Lancet 1996;348:1329–1339.&NA;A randomized, blinded, trial of clopidogrel versus aspirin in patients at risk of ischemic events (CAPRIE). CAPRIE Steering Committee.Lancet19963481329-133951. Reilly MP, Mohler ER III. Cilostazol: treatment of intermittent claudication. Ann Pharmacother 2001;35:48–56.ReillyMP]]MohlerERIIICilostazol: treatment of intermittent claudication.Ann Pharmacother20013548-5652. Thompson PD, Zimet R, Forbes WP, et al. Meta-analysis of results from eight randomized, placebo-controlled trials on the effect of cilostazol on patients with intermittent claudication. Am J Cardiol 2002;90:1314–1319.ThompsonPD]]ZimetR]]ForbesWP&etal;Meta-analysis of results from eight randomized, placebo-controlled trials on the effect of cilostazol on patients with intermittent claudication.Am J Cardiol2002901314-131953. Clagett GP, Sobel M, Jackson MR, et al. Antithrombotic therapy in peripheral arterial occlusive disease. The seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest. 2004;126:609S–626S.ClagettGP]]SobelM]]JacksonMR&etal;Antithrombotic therapy in peripheral arterial occlusive disease. The seventh ACCP conference on antithrombotic and thrombolytic therapy.Chest2004126609S-626S54. Lehert P, Comte S, Gamand S, et al. Naftidrofuryl in intermittent claudication: a retrospective analysis. J Cardiovasc Pharmacol 1994;23(suppl 3):S48–S52.LehertP]]ComteS]]GamandS&etal;Naftidrofuryl in intermittent claudication: a retrospective analysis.J Cardiovasc Pharmacol199423S48-S5255. Moody AP, al-Khaffaf HS, Lehert P, et al. An evaluation of patients with severe intermittent claudication and the effect of treatment with naftidrofuryl. J Cardiovasc Pharmacol 1994;23(suppl 3):S44–S47.MoodyAP]]al-KhaffafHS]]LehertP&etal;An evaluation of patients with severe intermittent claudication and the effect of treatment with naftidrofuryl.J Cardiovasc Pharmacol199423S44-S4756. Girolami B, Bernardi E, Prins MH, et al. Treatment of intermittent claudication with physical training, smoking cessation, pentoxifylline, or nafronyl: a meta-analysis. Arch Intern Med 1999;159:337–345.GirolamiB]]BernardiE]]PrinsMH&etal;Treatment of intermittent claudication with physical training, smoking cessation, pentoxifylline, or nafronyl: a meta-analysis.Arch Intern Med1999159337-34557. Avellone G, Mandalà V, Pinto A, et al. Clinical evaluation of short-term defibrotide treatment of patients with atherosclerosis obliterans of the lower limbs. Haemostasis 1986;16(suppl 1):55–58.AvelloneG]]MandalàV]]PintoA&etal;Clinical evaluation of short-term defibrotide treatment of patients with atherosclerosis obliterans of the lower limbs.Haemostasis19861655-5858. Brass EP, Anthony R, Cobb FR, et al. The novel phosphodiesterase inhibitor NM-702 improves claudication-limited exercise performance in patients with peripheral arterial disease. J Am Coll Cardiol 2006;48:2539–2545.BrassEP]]AnthonyR]]CobbFR&etal;The novel phosphodiesterase inhibitor NM-702 improves claudication-limited exercise performance in patients with peripheral arterial disease.J Am Coll Cardiol2006482539-254559. Nenci GG, Gresele P, Ferrari G, et al; Mesoglycan Intermittent Claudication group. Treatment of intermittent claudication with mesoglycan—a placebo-controlled, double-blind study. Thromb Haemost 2001;86:1181–1187.NenciGG]]GreseleP]]FerrariG&etal;Mesoglycan Intermittent Claudication groupTreatment of intermittent claudication with mesoglycan—a placebo-controlled, double-blind study.Thromb Haemost2001861181-118760. Takeshita S, Zheung LP, Brogi E, et al. Therapeutic angiogenesis: A single intra-arterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hindlimb model. J Clin Invest 1994;93:662–670.TakeshitaS]]ZheungLP]]BrogiE&etal;Therapeutic angiogenesis: A single intra-arterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hindlimb model.J Clin Invest199493662-67061. Lederman RJ, Mendelsohn FO, Anderson RD, et al; TRAFFIC investigators. Therapeutic angiogenesis with recombinant fibroblast growth factor-2 for intermittent claudication (the TRAFFIC study): a randomised trial. Lancet 2002;359:2053–2058.LedermanRJ]]MendelsohnFO]]AndersonRD&etal;TRAFFIC investigatorsTherapeutic angiogenesis with recombinant fibroblast growth factor-2 for intermittent claudication (the TRAFFIC study): a randomised trial.Lancet20023592053-205862. Rajagopalan S, Mohler ER III, Lederman RJ, et al. Regional angiogenesis with vascular endothelial growth factor in peripheral arterial disease: a phase II randomized, double-blind, controlled study of adenoviral delivery of vascular endothelial growth factor 121 in patients with disabling intermittent claudication. Circulation 2003;108:1933–1938.RajagopalanS]]MohlerERIII]]LedermanRJ&etal;Regional angiogenesis with vascular endothelial growth factor in peripheral arterial disease: a phase II randomized, double-blind, controlled study of adenoviral delivery of vascular endothelial growth factor 121 in patients with disabling intermittent claudication.Circulation20031081933-193863. Wolf GL, Wilson SE, Cross AP, et al. Surgery or balloon angioplasty for peripheral vascular disease: a randomized clinical trial. J Vasc Interv Radiol 1993;4:639–648.WolfGL]]WilsonSE]]CrossAP&etal;Surgery or balloon angioplasty for peripheral vascular disease: a randomized clinical trial.J Vasc Interv Radiol19934639-64864. Gardiner GA Jr, Meyerovitz MF, Stokes KR, et al. Complications of transluminal angioplasty. Radiology 1986;159:201–208.GardinerGAJr]]MeyerovitzMF]]StokesKR&etal;Complications of transluminal angioplasty.Radiology1986159201-20865. Vroegindeweij D, Vos LD, Tielbeek AV, et al. Balloon angioplasty combined with primary stenting versus balloon angioplasty alone in femoropopliteal obstructions: a comparative randomized study. Cardiovasc Intervent Radiol 1997;20:420–425.VroegindeweijD]]VosLD]]TielbeekAV&etal;Balloon angioplasty combined with primary stenting versus balloon angioplasty alone in femoropopliteal obstructions: a comparative randomized study.Cardiovasc Intervent Radiol199720420-42566. Zdanowski Z, Albrechtsson U, Lundin A, et al. Percutaneous transluminal angioplasty with or without stenting for femoropopliteal occlusions. A randomized controlled study. Int Angiol 1999;18:251–255.ZdanowskiZ]]AlbrechtssonU]]LundinA&etal;Percutaneous transluminal angioplasty with or without stenting for femoropopliteal occlusions. A randomized controlled study.Int Angiol199918251-25567. DeBakey ME, Glaeser DH. Patterns of atherosclerosis: effect of risk factors on recurrence and survival-analysis of 11,890 cases with more than 25-year follow-up. Am J Cardiol 2000;85:1045–1053.DeBakeyME]]GlaeserDHPatterns of atherosclerosis: effect of risk factors on recurrence and survival-analysis of 11,890 cases with more than 25-year follow-up.Am J Cardiol2000851045-1053