Peripheral vascular disease
|Peripheral vascular disease|
|Classification and external resources|
Peripheral vascular disease (PVD), commonly referred to as peripheral artery disease (PAD) or peripheral artery occlusive disease (PAOD) or peripheral obliterative arteriopathy, refers to the obstruction of large arteries not within the coronary, aortic arch vasculature, or brain. PVD can result from atherosclerosis, inflammatory processes leading to stenosis, an embolism, or thrombus formation. It causes either acute or chronic ischemia (lack of blood supply). Often PVD is a term used to refer to atherosclerotic blockages found in the lower extremity.
PVD also includes a subset of diseases classified as microvascular diseases resulting from episodal narrowing of the arteries (Raynaud's phenomenon), or widening thereof (erythromelalgia), i.e. vascular spasms.
- Stage I: Asymptomatic, incomplete blood vessel obstruction
- Stage II: Mild claudication pain in limb
- Stage IIA: Claudication at a distance of greater than 200 metres
- Stage IIB: Claudication distance of less than 200 metres
A more recent classification by Rutherford consists of four grades and seven categories:
- Grade 0, Category 0: Asymptomatic
- Grade I, Category 1: Mild claudication
- Grade I, Category 2: Moderate claudication
- Grade I, Category 3: Severe claudication
- Grade II, Category 4: Rest pain
- Grade III, Category 5: Minor tissue loss; Ischemic ulceration not exceeding ulcer of the digits of the foot
- Grade IV, Category 6: Major tissue loss; Severe ischemic ulcers or frank gangrene
About 20% of patients with mild PAD may be asymptomatic; other symptoms include:
- Claudication—pain, weakness, numbness, or cramping in muscles due to decreased blood flow
- Sores, wounds, or ulcers that heal slowly or not at all
- Noticeable change in color (blueness or paleness) or temperature (coolness) when compared to the other limb (termed unilateral dependent rubor; when both limbs are affected this is termed bilateral dependent rubor)
- Diminished hair and nail growth on affected limb and digits
- Smoking – tobacco use in any form is the single most important modifiable cause of PVD internationally. Smokers have up to a tenfold increase in relative risk for PVD in a dose-related effect. Exposure to second-hand smoke from environmental exposure has also been shown to promote changes in blood vessel lining (endothelium) which is a precursor to atherosclerosis.Smokers are 2 to 3 times more likely to have lower extremity peripheral arterial disease than coronary artery disease. More than 80%-90% of patients with lower extremity peripheral arterial disease are current or former smokers. The risk of PAD increases with the number of cigarettes smoked per day and the number of years smoked.
- Diabetes mellitus - causes between two and four times increased risk of PVD by causing endothelial and smooth muscle cell dysfunction in peripheral arteries. The risk of developing lower extremity peripheral arterial disease is proportional to the severity and duration of diabetes. Diabetics account for up to 70% of nontraumatic amputations performed, and a known diabetic who smokes runs an approximately 30% risk of amputation within 5 years.
- Dyslipidemia (high low density lipoprotein [LDL] cholesterol, low high density lipoprotein [HDL] cholesterol) - elevation of total cholesterol, LDL cholesterol, and triglyceride levels each have been correlated with accelerated PAD. Correction of dyslipidemia by diet and/or medication is associated with a major improvement in rates of heart attack and stroke. This benefit is gained even though current evidence does not demonstrate a major reversal of peripheral and/or coronary atherosclerosis.
- Hypertension - elevated blood pressure is correlated with an increase in the risk of developing PAD, as well as in associated coronary and cerebrovascular events (heart attack and stroke).Hypertension increased the risk of intermittent claudication 2.5- to 4-fold in men and women,respectively
- Risk of PAD also increases in individuals who are over the age of 50, male, obese, heart attack, or stroke. or with a family history of vascular disease
- Other risk factors which are being studied include levels of various inflammatory mediators such as C-reactive protein,fibrinogen, homocysteine, hyperviscosity, hypercoagulable state.
- All patients who have leg symptoms with exertion (suggestive of claudication) or ischemic rest pain.
- All patients aged 65 years and over regardless of risk factor status.
- All patients between the age of 50 to 69 and who have a cardiovascular risk factor (particularly diabetes or smoking).
- Age less than 50 years, with diabetes and one other atherosclerosis risk factor (smoking, dyslipidemia, hypertension, or hyperhomocysteinemia).
- Abnormal lower extremity pulse examination.
- Known atherosclerotic coronary, carotid, or renal artery disease.
- All patients with a Framingham risk score 10%-20%
- All patients who have previously experienced chest pain
Upon suspicion of PVD, the first-line study is the ankle brachial pressure index (ABPI/ABI). When the blood pressure readings in the ankles is lower than that in the arms, blockages in the arteries which provide blood from the heart to the ankle are suspected. Normal ABI range of 1.00 to 1.40.The patient is diagnosed with PAD when the ABI is ≤ 0.90 . ABI values of 0.91 to 0.99 are considered ‘‘borderline’’ and values >1.40 indicate noncompressible arteries. PAD is graded as mild to moderate if the ABI is between 0.41 and 0.90, and an ABI less than 0.40 is suggestive of severe PAD. These relative categories have prognostic value
In patients with suspected PAD but normal resting ABIs, exercise testing of ABI can be done. A base line ABI is obtained prior to exercise. The patient is then asked to exercise (usually patients are made to walk on a treadmill at a constant speed) until claudication pain occurs (or a maximum of 5 minutes), following which the ankle pressure is again measured. A decrease in ABI of 15%-20%would be diagnostic of PAD .
It is possible for conditions which stiffen the vessel walls (such as calcifications that occur in the setting of long term diabetes) to produce false negatives usually, but not always, indicated by abnormally high ABIs (> 1.40). Such results and suspicions merit further investigation and higher level studies.
If ABIs are abnormal the next step is generally a lower limb doppler ultrasound examination to look at site and extent of atherosclerosis. Other imaging can be performed by angiography, where a catheter is inserted into the common femoral artery and selectively guided to the artery in question. While injecting a radiodense contrast agent an X-ray is taken. Any flow limiting stenoses found in the x-ray can be identified and treated by atherectomy, angioplasty or stenting. Contrast angiography is the most readily available and widely used imaging technique.
Modern multislice computerized tomography (CT) scanners provide direct imaging of the arterial system as an alternative to angiography. CT provides complete evaluation of the aorta and lower limb arteries without the need for an angiogram's arterial injection of contrast agent.
Magnetic resonance angiography (MRA) is a noninvasive diagnostic procedure that uses a combination of a large magnet, radio frequencies, and a computer to produce detailed images to provide pictures of blood vessels inside the body. The advantages of MRA include its safety and ability to provide high-resolution three-dimensional (3D) imaging of the entire abdomen, pelvis and lower extremities in one sitting.
Dependent on the severity of the disease, the following steps can be taken:
- Smoking cessation (cigarettes promote PVD and are a risk factor for cardiovascular disease).
- Management of diabetes.
- Management of hypertension.
- Management of cholesterol, and medication with antiplatelet drugs. Medication with aspirin, clopidogrel and statins, which reduce clot formation and cholesterol levels, respectively, can help with disease progression and address the other cardiovascular risks that the patient is likely to have.
- Regular exercise for those with claudication helps open up alternative small vessels (collateral flow) and the limitation in walking often improves. Treadmill exercise (35 to 50 minutes, 3 to 4 times per week) has been reviewed as another treatment with a number of positive outcomes including reduction in cardiovascular events and improved quality of life.
- Cilostazol or pentoxifylline  treatment to relieve symptoms of claudication.
Treatment with other drugs or vitamins are unsupported by clinical evidence, "but trials evaluating the effect of folate and vitamin B-12 on hyperhomocysteinaemia, a putative vascular risk factor, are near completion".
After a trial of the best medical treatment outline above, if symptoms remain unnacceptable, patients may be referred to a vascular or endovascular surgeon; however, "No convincing evidence supports the use of percutaneous balloon angioplasty or stenting in patients with intermittent claudication".
- Angioplasty (PTA or percutaneous transluminal angioplasty) can be done on solitary lesions in large arteries, such as the femoral artery, but angioplasty may not have sustained benefits. Patency rates following angioplasty are highest for iliac arteries, and decrease with arteries towards the toes. Other criteria that affect outcome following revascularization are length of lesion, and number of lesions.
- Plaque excision, in which the plaque is scraped off of the inside of the vessel wall.
- Occasionally, bypass grafting is needed to circumvent a seriously stenosed area of the arterial vasculature. Generally, the saphenous vein is used, although artificial (Gore-Tex) material is often used for large tracts when the veins are of lesser quality.
- Rarely, sympathectomy is used – removing the nerves that make arteries contract, effectively leading to vasodilatation.
- When gangrene of the toes has set in, amputation is often a last resort to stop infected dying tissues from causing septicemia.
- Arterial thrombosis or embolism has a dismal prognosis, but is occasionally treated successfully with thrombolysis.
Several different guideline standards have been developed, including:
- TASC II Guidelines
Individuals with PAD have an "exceptionally elevated risk for cardiovascular events and the majority will eventually die of a cardiac or cerebrovascular etiology"; prognosis is correlated with the severity of the PAD as measured by the Ankle brachial pressure index (ABPI). Large-vessel PAD increases mortality from cardiovascular disease significantly. PAD carries a greater than "20% risk of a coronary event in 10 years".
There is a low risk that an individual with claudication will develop severe ischemia and require amputation, but the risk of death from coronary events is three to four times higher than matched controls without claudication. Of patients with intermittent claudication, only "7% will undergo lower extremity bypass surgery, 4% major amputations, and 16% worsening claudication", but stroke and heart attack events are elevated, and the "5-year mortality rate is estimated to be 30% (versus 10% in controls)".
The prevalence of peripheral vascular disease in the general population is 12–14%, affecting up to 20% of those over 70; 70%–80% of affected individuals are asymptomatic; only a minority ever require revascularisation or amputation. Peripheral vascular disease affects 1 in 3 diabetics over the age of 50.
In the USA peripheral arterial disease affects 12–20 percent of Americans age 65 and older. Approximately 10 million Americans have PVD. Despite its prevalence and cardiovascular risk implications, only 25 percent of PAD patients are undergoing treatment.
The incidence of symptomatic PVD increases with age, from about 0.3% per year for men aged 40–55 years to about 1% per year for men aged over 75 years. The prevalence of PVD varies considerably depending on how PAD is defined, and the age of the population being studied. Diagnosis is critical, as people with PAD have a four to five times higher risk of heart attack or stroke.
The Diabetes Control and Complications Trial and U.K. Prospective Diabetes Study trials in people with type 1 and type 2 diabetes, respectively, demonstrated that glycemic control is more strongly associated with microvascular disease than macrovascular disease. It may be that pathologic changes occurring in small vessels are more sensitive to chronically elevated glucose levels than is atherosclerosis occurring in larger arteries.
- Peripheral Arterial Disease at Merck Manual of Diagnosis and Therapy Professional Edition. Retrieved August 9, 2010.
- Fontaine R, Kim M, Kieny R (1954). "Die chirugische Behandlung der peripheren Durchblutungsstörungen. (Surgical treatment of peripheral circulation disorders)". Helvetica Chirurgica Acta (in German) 21 (5/6): 499–533. PMID 14366554.
- TASC II Guidelines
* Norgren L, Hiatt WR, Dormandy JA (2007). "Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II)". Eur J Vasc Endovasc Surg. 33 (Suppl 1): S1–75. doi:10.1016/j.ejvs.2006.09.024. PMID 17140820.
* Norgren L, Hiatt WR, Dormandy JA, TASC II Working Group et al. (2007). "Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II)". J Vasc Surg. 45 (Suppl S): S5–67. doi:10.1016/j.jvs.2006.12.037. PMID 17223489.
* Norgren L, Hiatt WR, Dormandy JA (2007). "Inter-Society Consensus for the Management of Peripheral Arterial Disease". Int Angiol. 26 (2): 81–157. PMID 17489079.
- Joosten MM, Pai JK, Bertoia ML, Rimm EB, Spiegelman D, Mittleman MA, Mukamal KJ. Associations between conventional cardiovascular risk factors and risk of peripheral artery disease in men. JAMA. 2012 Oct 24;308(16):1660-7. doi: 10.1001/jama.2012.13415 PMID 23093164
- Price J, Mowbray P, Lee A, Rumley A, Lowe G, Fowkes F: Relationship between smoking and cardiovascular risk factors in the development of peripheral arterial disease and coronary artery disease; Edinburgh Artery Study Edinburgh Artery Study. European heart journal 1999, 20(5):344-353.
- Smith GD, Shipley M, Rose G: Intermittent claudication, heart disease risk factors, and mortality. The Whitehall Study. Circulation 1990, 82(6):1925-1931.
- Cole C, Hill G, Farzad E, Bouchard A, Moher D, Rody K, Shea B: Cigarette smoking and peripheral arterial occlusive disease. Surgery 1993, 114(4):753.
- Hirsch AT, Haskal ZJ, Hertzer NR, Bakal, Curtis W., Creager, Mark A., Halperin, Jonathan L., Hiratzka, Loren F., Murphy, William R.C., Olin, Jeffrey W. (2006). "ACC/AHA 2005 guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): executive summary 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". J. Am. Coll. Cardiol. 47 (6): 1239–312. doi:10.1016/j.jacc.2005.10.009. PMID 16545667.
- Kannel WB, McGee D: Diabetes and glucose tolerance as risk factors for cardiovascular disease: the Framingham study. Diabetes care 1979, 2(2):120-126.
- Creager MA, Lüscher TF, Cosentino F, Beckman JA: Diabetes and vascular disease pathophysiology, clinical consequences, and medical therapy: part I. Circulation 2003, 108(12):1527-1532.
- Lüscher TF, Creager MA, Beckman JA, Cosentino F: Diabetes and vascular disease pathophysiology, clinical consequences, and medical therapy: Part II. Circulation 2003, 108(13):1655-1661.
- Beks P, Mackaay A, De Neeling J, De Vries H, Bouter L, Heine R: Peripheral arterial disease in relation to glycaemic level in an elderly Caucasian population: the Hoorn study. Diabetologia 1995, 38(1):86-96.
- Unit ES: Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins. Lancet 2005, 366:1267-1278.
- Kannel W, McGee D: Update on some epidemiologic features of intermittent claudication: the Framingham Study. Journal of the American Geriatrics Society 1985, 33(1):13
- 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(6):738-743.
- Hooi JD, Kester AD, Stoffers HE, Overdijk MM, van Ree JW, Knottnerus JA: Incidence of and risk factors for asymptomatic peripheral arterial occlusive disease: a longitudinal study. American journal of epidemiology 2001, 153(7):666-672.
- Allison MA, Denenberg JO, Criqui MH: Family History of Peripheral Artery Disease Is Associated With Prevalence and Severity of Peripheral Artery Disease. Journal of the American College of Cardiology 2011, 58(13).
- Valentine RJ, Guerra R, Stephan P, Scoggins E, Clagett GP, Cohen J: Family history is a major determinant of subclinical peripheral arterial disease in young adults. Journal of vascular surgery 2004, 39(2):351-356
- Ridker PM, Stampfer MJ, Rifai N: Novel risk factors for systemic atherosclerosis. JAMA: the journal of the American Medical Association 2001, 285(19):2481-2485
- Rooke TW, Hirsch AT, Misra S, Sidawy AN, Beckman JA, Findeiss LK, Golzarian J, Gornik HL, Halperin JL, Jaff MR: 2011 ACCF/AHA focused update of the guideline for the management of patients with peripheral artery disease (updating the 2005 guideline) a report of the American college of cardiology foundation/American heart association task force on practice guidelines. Journal of the American College of Cardiology 2011, 58(19):2020-2045.
- Vowden P, Vowden K (March 2001). "Doppler assessment and ABPI: Interpretation in the management of leg ulceration". Worldwide Wounds. - describes ABPI procedure, interpretation of results, and notes the somewhat arbitrary selection of "ABPI of 0.8 has become the accepted endpoint for high compression therapy, the trigger for referral for a vascular surgical opinion and the defining upper marker for an ulcer of mixed aetiology"
- Leiner T, Kessels AG, Nelemans PJ, Vasbinder GB, de Haan MW, Kitslaar PE, Ho KY, Tordoir JH, van Engelshoven JM699-708 (May 2005). "Peripheral arterial disease: comparison of color duplex US and contrast-enhanced MR angiography for diagnosis". Radiology 235 (2): 699–708. doi:10.1148/radiol.2352040089. PMID 15858107.
- Leiner, T (February 2005). "Magnetic resonance angiography of abdominal and lower extremity vasculature". Top Magn Reson Imaging 16 (1): 21–66. PMID 16314696.
- Burns P, Gough S, Bradbury AW (March 2003). "Management of peripheral arterial disease in primary care". BMJ 326 (7389): 584–8. doi:10.1136/bmj.326.7389.584. PMC 1125476. PMID 12637405.
- Robless P, Mikhailidis DP, Stansby GP (2008). "Cilostazol for peripheral arterial disease". In Robless, Peter. Cochrane Database Syst Rev (1): CD003748. doi:10.1002/14651858.CD003748.pub3. PMID 18254032.
- Salhiyyah, Kareem; Senanayake, Eshan; Abdel-Hadi, Mohammed; Booth, Andrew; Michaels, Jonathan A (2012). Pentoxifylline for intermittent claudication. In Salhiyyah, Kareem. "Cochrane Database of Systematic Reviews". Cochrane Database Syst Rev 1: CD005262. doi:10.1002/14651858.CD005262.pub2. PMID 22258961.
- Fowkes FG, Gillespie IN (2000). "Angioplasty (versus non surgical management) for intermittent claudication". In Fowkes, Gerry. Cochrane Database Syst Rev (2): CD000017. doi:10.1002/14651858.CD000017. PMID 10796469.
- Twine CP, Coulston J, Shandall A, McLain AD (2009). "Angioplasty versus stenting for superficial femoral artery lesions". In Twine, Christopher P. Cochrane Database Syst Rev (2): CD006767. doi:10.1002/14651858.CD006767.pub2. PMID 19370653.
- Johnston KW, Rae M, Hogg-Johnston SA, Colapinto RF, Walker PM, Baird RJ, Sniderman KW, Kalman P: 5-year results of a prospective study of percutaneous transluminal angioplasty. Annals of surgery 1987, 206(4):403.
- Emmerich J: Current state and perspective on medical treatment of critical leg ischemia: gene and cell therapy. The international journal of lower extremity wounds 2005, 4(4):234-241.
- Shammas NW (2007). "Epidemiology, classification, and modifiable risk factors of peripheral arterial disease". Vasc Health Risk Manag 3 (2): 229–34. doi:10.2147/vhrm.2007.3.2.229. PMC 1994028. PMID 17580733.
- Selvin E, Wattanakit K, Steffes MW, Coresh J, Sharrett AR (April 2006). "HbA1c and peripheral arterial disease in diabetes: the Atherosclerosis Risk in Communities study". Diabetes Care 29 (4): 877–82. doi:10.2337/diacare.29.04.06.dc05-2018. PMID 16567831.
- "Peripheral Arterial Disease" at the National Heart, Lung and Blood Institute
- Peripheral Arterial Disease (P.A.D.) at the American College of Foot and Ankle Surgeons