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peripheral arterial disease; peripheral artery atherosclerosis (PAD)

Also see - internal carotid artery disease - intermittent claudication Etiology: 1) risk factors the same as for coronary artery disease [2] 2) in middle age & older men, major risk factors include: a) smoking b) hypertension - each 20 mm Hg increase in systolic BP & each 10 mm Hg increase in diastolic BP is associated with 63% & 35% higher risks for PAD [37] c) hypercholesterolemia d) diabetes mellitus type 2 [17] 3) less common causes include [45] - adventitial cystic disease - arterial dissection - endofibrosis - fibromuscular dysplasia - popliteal artery aneurysm - popliteal entrapment syndrome - radiation arteritis - thromboembolism - vasculitis Epidemiology: 1) 29% of patients who smoke or have diabetes [3] (40% of these same patients had coronary artery disease) 2) 9% of patients with PVD have symptomatic claudication [3] 3) 20% of patients > 70 Pathology: - most commonly involves the lower extremities [1] - part of a larger process involving atherosclerosis of the aorta & its branches [1] - patients appear to develop a metabolic myopathy & axonal polyneuropathy related to chronic lower extremity ischemia resulting in abnormal biomechanics prior to the onset of pain [13] - increased plasma levels of trimethylamine N-oxide increases mortality in patients with PAD [40] Genetics: - implicated genes - CHRNA3 (peripheral arterial occlusive disease type 2) Clinical manifestations: 1) signs of asymptomatic disease a) ankle to brachial index < 0.9 (lower extremity disease) b) carotid bruit or diminished carotid pulse c) femoral bruit d) reduced exercise capacity e) most patients are asymptomatic 2) intermittent claudication is a sign of symptomatic disease - pain, paresthesias, pallor, paralysis, pulselessness [1] - exertional leg pain that improves quickly (within 5 minutes) with rest (see intermittent claudication) 3) abnormalities in torque & power at the hip, knee, & ankle immediately upon walking (before onset of pain) 4) unequal brachial blood pressure - systolic blood pressure difference of >= 15 mm Hg between arms may be associated with PAD of subclavian artery [16] - if occlusion occurs proximal to the origin of the vertebral artery, retrograde blood flow from the CNS to the arm results in subclavian steal syndrome [1] 5) abdominal pulse may be due to abdominal aortic aneurysm [1] 6) diminished peripheral pulses 7) elevation pallor & dependent rubor [1] - may be associated with mild dependent edema 8) non-healing leg ulcers 9) tendinous xanthoma [1] * also see carotid artery disease Special laboratory: - echocardiogram: embolic source of ischemia - ankle/brachial index (ABI) of < 0.9 is diagnostic of PAD - ABI > 1.4 is uninterpretable, due to non-compressible arteries - obtain toe to brachial index - exercise ABI if resting ABI is equivocal - an ABI decrease of 20% after exercise suggests PAD [1] - bilateral brachial blood pressure for upper extremity PAD [1] * video [49] Radiology: 1) screening [10] a) ultrasound, ankle-brachial index b) contrast-enhanced MRI best 95% sensitivity, 97% specificity [14] 2) CT angiography or MRI angiography - failure of medical therapy, including supervised exercise - identifies vascular pathology & aids in planning revascularization [1] * video [49] Differential diagnosis: - lumbar spinal stenosis - chronic exertional compartment syndrome - also see intermittent claudication for distingushing features Complications: - acute limb ischemia - chronic limb-threatening ischemia - arterial ulcers* - often painful - frequently occur where collateral circulation is minimal - anterior lower leg, distal toes - predictive of other comorbid cardiovascular disease - coronary artery disease - cerebrovascular disease [26] - annual risk of cardiovascular event(s) is 5-7% [1]* - 50% increase in risk of cardiovascular events [37]* * risk of myocardial infarction > arterial ulcers [59] Management: 1) acute arterial ischemia a) start heparin b) consult vascular surgery [1] 2) diet & life-style modification (see CAD) a) exercise training & rehabilitation [1,22] - structured, supervised exercise program most effective treatment [1,32,41] - high-intensity walking therapy is the standard of care; - it is superior to low-intensity walking [55] - a home-based exercise intervention consisting of a wearable activity monitor & telephone coaching, did not improve walking performance at 9-month follow-up [48] - home-based, behavior-change program improved 6-minute walking distance by ~25 meters [57] b) smoking cessation c) avoid second-hand smoke [41] d) fruits & vegetable consumption may lower risk [42] e) nut consumption may lower risk [43] 3) control blood pressure - target systolic BP of 135-145 mm Hg & diastolic BP of 60-90 mm Hg [23] 4) control diabetes mellitus 5) pharmaceutical agents a) treat dyslipidemia (see CAD) [6] - high-intensity statin therapy - 40-80 mg atorvastatin QD or 20-40 mg rosuvastatin QD - 80 mg of atorvastatin may improve pain-free walking time (without effect on ankle to brachial index) [5] - 40 mg simvastatin diminished risk of major vascular events in patients with peripheral arterial disease (5-6%) [8] - target LDL < 70 mg/dL [62] - statins reduce progression of arterial stiffness in Chinese as assessed by brachial-ankle pulse wave velocity [58] b) antiplatelet agents 1] monotherapy, no evidence to support dual anti-platelet therapy [1] 2] recommended for all symptomatic patients [1] 3] aspirin a] of no benefit (statistically) [11]; uncertain benefit [15] b] preferred over clopidogrel [1] c] reduces risk for myocardial infarction, stroke, & acute limb ischemia [1] 4] dipyridamole/aspirin (Aggrenox) 5] clopidogrel (Plavix) unless patient is taking aspirin 6] ticagrelor (Brilinta) no better than clopidogrel [39] 7] no benefit of added warfarin; potential harm [1,9,15] 8] rivaroxaban 2.5 mg BID + aspirin 100 mg/day decreases cardiovascular events (RR=0.72) at the cost of increased risk of bleeding (mostly GI bleeding) (RR=1.6) [46] - recommended by AHA/ACC if not at increased bleeding risk [62] 9] anticoagulation is not indicated in the absence of symptomatic limb ischemia [50] c) ACE inhibitors 1] reduce risk of myocardial infarction & stroke in patients with peripheral arterial disease [4] 2] improve walking distance in patients with peripheral arterial disease [18,19] d) cilostazol rather than pentoxifylline for intermittent claudication 1] contraindicated in heart failure (HFrEF) 2] achieves benefits in walking distance sustained at 24 weeks [1,30] 3] preferred option prior to referral to vascular surgery [1] e) in patients with type 2 diabetes GLP-1 agonists & SGLT-2 inhibitors reduce major cardiovascular events [62] f) beta-blockers are not contraindicated g) Ginkgo biloba may be of benefit h) GM-CSF of no benefit [44] see secondary prevention in patients with cardiovascular disease 6) angioplasty or surgery (lower extremity revascularization) a) failure of medical therapy, including supervised exercise & cilostazol [1] b) pain at rest c) poorly healing ulcers d) critical limb ischemia (urgent) e) peripheral artery bypass f) endovascular stenting for aortoiliac occlusion [1] - conflicting data on mortality with use of paclitaxel-eluting stents [54] g) endarterectomy with passible surgical patch repair for common femoral artery occlusion [1] h) paclitaxel-coated angioplasty balloon catheter (Lutonix DCB) FDA-approved for superficial femoral artery & popliteal artery occlusion [28] - apparent lack of benefit for women i) 54-55% 3-year mortality in patients after endovascular revascularization [56] j) higher rates of adverse outomes with angioplasty, stenting, atherectomy ' within 6 months of diagnosis unless limb-threatening ischemia [60] 7) annual influenza vaccination [41] 8) screening for peripheral arterial disease (asymptomatic) a) age >= 50 years & history of diabetes mellitus or smoking b) age >= 65 years c) evidence insufficient to support screening [25,47] Notes: - European Society of Cardiology guidelines [63]

Interactions

disease interactions

Related

ankle-brachial index (ABI) or ankle-arm index (AAI) arterial ulcer carotid artery disease coronary artery disease; coronary atherosclerosis (CAD) peripheral vascular system screening for peripheral arterial disease secondary prevention in patients with cardiovascular disease vertebrobasilar disease

Specific

atheroembolism; cholesterol embolism; aortic atheroembolism critical limb ischemia intermittent claudication; vascular claudication; Charcot's syndrome; myasthenia angiosclerotica

General

arterial occlusive disease peripheral vascular disease (PVD)

Database Correlations

OMIM 612052

References

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