Peripheral arterial disease: Epidemiology, natural history, diagnosis and treatment

Lower extremity peripheral arterial disease (PAD) affects approximately 10% of the American population, with 30% to 40% of these patients presenting with claudication symptoms. The prevalence of PAD increases with age and the number of vascular risk factors. More importantly, it is a marker of atherosclerotic disease burden, and is associated with increased mortality from cardiovascular and cerebrovascular causes. There have been recent advances in noninvasive imaging, endovascular approaches for revascularization, and aggressive risk factor management for prevention of cardiac and cerebrovascular complications in PAD. There is now a trend toward aggressive risk factor modification and endovascular revascularization for most patients, with surgical interventions reserved for certain situations only. In the present article, a systematic review is presented, focusing on the key aspects of the disease epidemiology, presentation, natural history, diagnosis and available management options.

[1]  K. Prasad,et al.  Suppression of hypercholesterolemic atherosclerosis by pentoxifylline and its mechanism. , 2007, Atherosclerosis.

[2]  Rodney A. White,et al.  ACC/AHA Guidelines for the Management of Patients with Peripheral Arterial Disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Associations for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Intervent , 2006, Journal of vascular and interventional radiology : JVIR.

[3]  A. Sharrett,et al.  HbA1c and peripheral arterial disease in diabetes: the Atherosclerosis Risk in Communities study. , 2006, Diabetes care.

[4]  J. Halperin,et al.  Limitation of the resting ankle-brachial index in symptomatic patients with peripheral arterial disease , 2006, Vascular medicine.

[5]  G. Lip,et al.  Antithrombotic therapy in peripheral arterial occlusive disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. , 2004, Chest.

[6]  Elizabeth Selvin,et al.  Prevalence of and Risk Factors for Peripheral Arterial Disease in the United States: Results From the National Health and Nutrition Examination Survey, 1999–2000 , 2004, Circulation.

[7]  Richard B Devereux,et al.  Relationship of High and Low Ankle Brachial Index to All-Cause and Cardiovascular Disease Mortality: The Strong Heart Study , 2004, Circulation.

[8]  Mark A. Creager,et al.  Cholesterol Reduction With Atorvastatin Improves Walking Distance in Patients With Peripheral Arterial Disease , 2003, Circulation.

[9]  W. Aronow,et al.  Effect of simvastatin versus placebo on treadmill exercise time until the onset of intermittent claudication in older patients with peripheral arterial disease at six months and at one year after treatment. , 2003, The American journal of cardiology.

[10]  F. S. Pereles,et al.  Safety of gadolinium contrast angiography in patients with chronic renal insufficiency. , 2003, Journal of vascular surgery.

[11]  Daniel W. Jones,et al.  The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. , 2003, JAMA.

[12]  Deepak L. Bhatt,et al.  Superficial femoral artery occlusion: nitinol stents achieve better flow and reduce the need for medications than balloon angioplasty alone. , 2003, The Journal of invasive cardiology.

[13]  P. Thompson,et al.  Meta-analysis of results from eight randomized, placebo-controlled trials on the effect of cilostazol on patients with intermittent claudication. , 2003, The American journal of cardiology.

[14]  J. Mckenney,et al.  National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) , 2002 .

[15]  K. Eagle,et al.  Missed Opportunities to Treat Atherosclerosis in Patients Undergoing Peripheral Vascular Interventions: Insights From the University of Michigan Peripheral Vascular Disease Quality Improvement Initiative (PVD-QI2) , 2002, Circulation.

[16]  Udo Hoffmann,et al.  Peripheral vascular occlusive disease: evaluation with contrast-enhanced moving-bed MR angiography versus digital subtraction angiography in 106 patients. , 2002, AJR. American journal of roentgenology.

[17]  Gerhard Ziemer,et al.  Sirolimus-Eluting Stents for the Treatment of Obstructive Superficial Femoral Artery Disease: Six-Month Results , 2002, Circulation.

[18]  P. De Cata,et al.  Extensive use of peripheral angioplasty, particularly infrapopliteal, in the treatment of ischaemic diabetic foot ulcers: clinical results of a multicentric study of 221 consecutive diabetic subjects , 2002, Journal of internal medicine.

[19]  Yi Wang,et al.  Peripheral vascular disease: combined 3D bolus chase and dynamic 2D MR angiography compared with x-ray angiography for treatment planning. , 2002, Radiology.

[20]  K. Kwon,et al.  Pharmacokinetic and pharmacodynamic modeling of the antiplatelet and cardiovascular effects of cilostazol in healthy humans , 2002, Clinical pharmacology and therapeutics.

[21]  D. Strandness,et al.  Effect of Cilostazol in Patients with Intermittent Claudication: A Randomized, Double-Blind, Placebo-Controlled Study , 2002, Vascular and endovascular surgery.

[22]  C. Altehoefer,et al.  Contrast enhanced MR angiography in the assessment of relevant stenoses in occlusive disease of the pelvic and lower limb arteries: diagnostic value of a two-step examination protocol in comparison to conventional DSA. , 2002, European journal of radiology.

[23]  Catherine Sudlow,et al.  Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients , 2002, BMJ : British Medical Journal.

[24]  M. Jaff,et al.  Tibioperoneal (Outflow Lesion) Angioplasty Can Be Used as Primary Treatment in 235 Patients With Critical Limb Ischemia: Five-Year Follow-Up , 2001, Circulation.

[25]  L. Sharma,et al.  Leg symptoms in peripheral arterial disease: associated clinical characteristics and functional impairment. , 2001, JAMA.

[26]  J. Birkmeyer,et al.  Cardiologists performing peripheral angioplasties: impact on utilization. , 2001, Effective clinical practice : ECP.

[27]  E. Mohler,et al.  Effects of cilostazol on resting ankle pressures and exercise-induced ischemia in patients with intermittent claudication , 2001, Vascular medicine.

[28]  M J Koelemay,et al.  Magnetic resonance angiography for the evaluation of lower extremity arterial disease: a meta-analysis. , 2001, JAMA.

[29]  D. Dawson,et al.  A comparison of cilostazol and pentoxifylline for treating intermittent claudication. , 2000, The American journal of medicine.

[30]  J. V. Engelshoven,et al.  Peripheral arterial disease: meta-analysis of the diagnostic performance of MR angiography. , 2000, Radiology.

[31]  P. Desgranges,et al.  Acute occlusion of popliteal and/or tibial arteries: the value of percutaneous treatment. , 2000, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[32]  N M Rofsky,et al.  Gadolinium-enhanced MR angiography: artifacts and pitfalls. , 2000, AJR. American journal of roentgenology.

[33]  N. Rofsky,et al.  MR angiography in the evaluation of atherosclerotic peripheral vascular disease. , 2000, Radiology.

[34]  S. Yusuf,et al.  Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. , 2000 .

[35]  D. Dawson,et al.  A new pharmacological treatment for intermittent claudication: results of a randomized, multicenter trial. , 1999, Archives of internal medicine.

[36]  M. Prins,et al.  Antithrombotic Drugs in the Primary Medical Management of Intermittent Claudication: A Meta-analysis , 1999, Thrombosis and Haemostasis.

[37]  H. Lau,et al.  Screening for asymptomatic carotid stenosis in patients with peripheral vascular disease: a prospective study and risk factor analysis. , 1999, Cardiovascular surgery.

[38]  Aker,et al.  A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. , 1999, The New England journal of medicine.

[39]  M. Prins,et al.  Treatment of intermittent claudication with physical training, smoking cessation, pentoxifylline, or nafronyl: a meta-analysis. , 1999, Archives of internal medicine.

[40]  J. Crouse,et al.  Effect of the novel antiplatelet agent cilostazol on plasma lipoproteins in patients with intermittent claudication. , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[41]  M. Jaff,et al.  The acute outcome of tibioperoneal vessel angioplasty in 417 cases with claudication and critical limb ischemia. , 1998, Catheterization and cardiovascular diagnosis.

[42]  R. Holman,et al.  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. , 1998 .

[43]  D. Dawson,et al.  Cilostazol has beneficial effects in treatment of intermittent claudication: results from a multicenter, randomized, prospective, double-blind trial. , 1998, Circulation.

[44]  M. Henry,et al.  Percutaneous endoluminal treatment of iliac occlusions: long-term follow-up in 105 patients. , 1998, Journal of endovascular surgery : the official journal of the International Society for Endovascular Surgery.

[45]  W. Aronow,et al.  Prevalence of Coronary Artery Disease, Atherothrombotic Brain Infarction, and Peripheral Arterial Disease: Associated Risk Factors in Older Hispanics in an Academic Hospital‐Based Geriatrics Practice , 1998, Journal of the American Geriatrics Society.

[46]  J. Kjekshus,et al.  Effect of simvastatin on ischemic signs and symptoms in the Scandinavian simvastatin survival study (4S). , 1998, The American journal of cardiology.

[47]  J. A. Herd,et al.  Effect of cilostazol on walking distances in patients with intermittent claudication caused by peripheral vascular disease. , 1998, Journal of vascular surgery.

[48]  J. Bosch,et al.  Meta-analysis of the results of percutaneous transluminal angioplasty and stent placement for aortoiliac occlusive disease. , 1997, Radiology.

[49]  L. Køber,et al.  Effect of angiotensin converting enzyme inhibition after acute myocardial infarction in patients with arterial hypertension , 1997 .

[50]  C. Fife,et al.  Infrapopliteal transcatheter interventions for limb salvage in diabetic patients: importance of aggressive interventional approach and role of transcutaneous oximetry. , 1997, Journal of the American College of Cardiology.

[51]  R. Ahmadi,et al.  Value of color duplex sonography for evaluation of tibioperoneal arteries in patients with femoropopliteal obstruction: a prospective comparison with anterograde intraarterial digital subtraction angiography. , 1997, Journal of vascular surgery.

[52]  M. Dennis A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee , 1996 .

[53]  D. Moher,et al.  Management of intermittent claudication with pentoxifylline: meta-analysis of randomized controlled trials. , 1996, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[54]  H. Buchwald,et al.  Impact of cholesterol reduction on peripheral arterial disease in the Program on the Surgical Control of the Hyperlipidemias (POSCH). , 1996, Surgery.

[55]  R. Tate,et al.  Value of toe pulse waves in addition to systolic pressures in the assessment of the severity of peripheral arterial disease and critical limb ischemia. , 1996, Journal of vascular surgery.

[56]  M. Law,et al.  An analysis of the effectiveness of interventions intended to help people stop smoking. , 1995, Archives of internal medicine.

[57]  A. Gardner,et al.  Exercise rehabilitation programs for the treatment of claudication pain. A meta-analysis. , 1995, JAMA.

[58]  J. Richardson,et al.  Intensive surveillance of femoropopliteal-tibial autogenous vein bypasses improves long-term graft patency and limb salvage. , 1995, Annals of surgery.

[59]  G. Lamas,et al.  Effects of captopril on ischemic events after myocardial infarction. Results of the Survival and Ventricular Enlargement trial. SAVE Investigators. , 1994, Circulation.

[60]  R. J. Valentine,et al.  Coronary artery disease is highly prevalent among patients with premature peripheral vascular disease. , 1994, Journal of vascular surgery.

[61]  G Cloutier,et al.  Limitations of ultrasonic duplex scanning for diagnosing lower limb arterial stenoses in the presence of adjacent segment disease. , 1994, Journal of vascular surgery.

[62]  Walker,et al.  Collaborative overview of randomised trials of antiplatelet therapy Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients , 1994 .

[63]  J. Polak,et al.  Ankle-arm index as a marker of atherosclerosis in the Cardiovascular Health Study. Cardiovascular Heart Study (CHS) Collaborative Research Group. , 1993, Circulation.

[64]  L. Kuller,et al.  Decreased ankle/arm blood pressure index and mortality in elderly women. , 1993, JAMA.

[65]  L. Kuller,et al.  Morbidity and mortality in hypertensive adults with a low ankle/arm blood pressure index. , 1993, JAMA.

[66]  Sadao Takahashi,et al.  Effect of Cilostazol, a Cyclic AMP Phosphodiesterase Inhibitor, on the Proliferation of Rat Aortic Smooth Muscle Cells in Culture , 1992, Journal of cardiovascular pharmacology.

[67]  J. Manson,et al.  Low-dose aspirin and subsequent peripheral arterial surgery in the Physicians' Health Study , 1992, The Lancet.

[68]  J. F. Whelan,et al.  Color flow doppler ultrasonography: Comparison with peripheral arteriography for the investigation of peripheral vascular disease , 1992, Journal of clinical ultrasound : JCU.

[69]  K. Radack,et al.  Beta-adrenergic blocker therapy does not worsen intermittent claudication in subjects with peripheral arterial disease. A meta-analysis of randomized controlled trials. , 1991, Archives of internal medicine.

[70]  R. Prescott,et al.  Edinburgh Artery Study: prevalence of asymptomatic and symptomatic peripheral arterial disease in the general population. , 1991, International journal of epidemiology.

[71]  L. Kuller,et al.  The ratio of ankle and arm arterial pressure as an independent predictor of mortality. , 1991, Atherosclerosis.

[72]  B. Eikelboom,et al.  Screening of the internal carotid arteries in patients with peripheral vascular disease by colour-flow duplex scanning. , 1991, European journal of vascular surgery.

[73]  D. Sacks,et al.  Evaluation of the peripheral arteries with duplex US after angioplasty. , 1990, Radiology.

[74]  L. Stavenow,et al.  Conservative drug treatment in patients with moderately severe chronic occlusive peripheral arterial disease. Scandinavian Study Group. , 1989, Circulation.

[75]  R. Lassila,et al.  Cigarette smoking and the outcome after lower limb arterial surgery. , 1988, Acta chirurgica Scandinavica.

[76]  F. Fowkes,et al.  The measurement of atherosclerotic peripheral arterial disease in epidemiological surveys. , 1988, International journal of epidemiology.

[77]  S. Shionoya,et al.  Noninvasive diagnostic techniques in vascular disease. , 1987, International angiology : a journal of the International Union of Angiology.

[78]  E. Barrett-Connor,et al.  TABLE 1 Prevalence of PAD by traditional assessment : intermittent claudication and pulse palpation % Claudication % Pulse abnormalities Rose Femoral Posterior Dorsalis n Rose , 2005 .

[79]  A. House,et al.  The effect of cessation of smoking on the accumulative survival rates of patients with symptomatic peripheral vascular disease , 1983, The Medical journal of Australia.

[80]  L. Cotton,et al.  The measured effect of stopping smoking on intermittent claudication , 1982, The British journal of surgery.

[81]  D. Strandness,et al.  Pentoxifylline efficacy in the treatment of intermittent claudication: multicenter controlled double-blind trial with objective assessment of chronic occlusive arterial disease patients. , 1982, American heart journal.

[82]  R. Rutherford,et al.  Combining segmental systolic pressures and plethysmography to diagnose arterial occlusive disease of the legs. , 1979, American journal of surgery.

[83]  G. Bone,et al.  Value of arterial pressure measurements in the proximal and distal part of the thigh in arterial occlusive disease. , 1978, Surgery, gynecology & obstetrics.

[84]  D. E. Szilagyi,et al.  Biologic Fate of Autogenous Vein lmplants as Arterial Substitutes: Clinical, Angiographic and Histopathologic Observations in Femoro‐Popliteal Operations for Atherosc erosis , 1973, Annals of surgery.

[85]  S. Carter Clinical measurement of systolic pressures in limbs with arterial occlusive disease. , 1969, JAMA.

[86]  S. Grundy,et al.  National Cholesterol Education Program Third Report of the National Cholesterol Education Program ( NCEP ) Expert Panel on Detection , Evaluation , and Treatment of High Blood Cholesterol in Adults ( Adult Treatment Panel III ) Final Report , 2022 .

[87]  M. Criqui,et al.  Peripheral arterial disease detection, awareness, and treatment in primary care. , 2001, JAMA.

[88]  R. Rutherford,et al.  Management of peripheral arterial disease (PAD). TASC Working Group. TransAtlantic Inter-Society Consensus (TASC). , 2000, Journal of Vascular Surgery.

[89]  G. Laub,et al.  Diabetes and peripheral arterial occlusive disease: prospective comparison of contrast-enhanced three-dimensional MR angiography with conventional digital subtraction angiography. , 2000, AJR. American journal of roentgenology.

[90]  L. Køber,et al.  Effect of angiotensin converting enzyme inhibition after acute myocardial infarction in patients with arterial hypertension. TRACE Study Group, Trandolapril Cardiac Event. , 1997, Journal of hypertension.

[91]  Effect of intensive diabetes management on macrovascular events and risk factors in the Diabetes Control and Complications Trial. , 1995, The American journal of cardiology.

[92]  Collaborative overview of randomised trials of antiplatelet therapy--I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists' Collaboration. , 1994, BMJ.

[93]  R. Prosser,et al.  The effect of postoperative smoking on femoropopliteal bypass grafts , 1989, Annals of vascular surgery.

[94]  A. Cross,et al.  Percutaneous transluminal angioplasty versus operation for peripheral arteriosclerosis. Report of a prospective randomized trial in a selected group of patients. , 1989, Journal of vascular surgery.

[95]  D. S. Martin Noninvasive Diagnostic Techniques in Vascular Disease. 3d ed , 1986 .

[96]  Sumner Ds,et al.  Toe blood pressure. A valuable adjunct to ankle pressure measurement for assessing peripheral arterial disease. , 1983 .

[97]  D S Sumner,et al.  Toe blood pressure. A valuable adjunct to ankle pressure measurement for assessing peripheral arterial disease. , 1983, The Journal of cardiovascular surgery.

[98]  T. Perera Femoral arteriography. , 1977, Radiography.