Peripheral Artery Disease: Causes and Consequences

PAD is a progressive, systemic disease resulting from the formation of atherosclerotic plaques in the peripheral arteries, causes stenosis and occlusion. PAD is often asymptomatic, but severe vascular obstruction can lead to limb ischaemia requiring amputation. Despite treatment involving antiplatelet therapy and lifestyle changes, patients with PAD are still at high risk of thrombotic events.

An overview of peripheral artery disease pathogenesis, epidemiology and management. 02:23 min
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Peripheral Artery Disease: Mechanism of Disease An overview of peripheral artery disease development and pathogenesis. 02:23 min
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The development of plaques in the arteries of the lower extremities, as a consequence of the systemic disease atherosclerosis, leads to PAD. PAD causes a spectrum of lower limb symptoms, but can often be asymptomatic. Patients with PAD have a high morbidity and mortality burden due to worsening of limb symptoms (which can lead to amputation) and potentially fatal, systemic atherothrombotic events (such as MI and stroke).

PAD treatment involves lifestyle changes, a structured exercise programme, drugs aimed at vascular protection and, in some instances, revascularization. Treatment is aimed at improving limb prognosis (improving symptoms and minimizing tissue loss) and preventing cardiovascular events (by improving cardiovascular risk factor control and preventing atherothrombosis). However, even with optimal treatment, which includes an antiplatelet agent and a statin in all patients with PAD, there remains a high residual risk of systemic and limb-related ischaemic events.

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In 2010, more than how many people worldwide were estimated to have lower extremity PAD?

As of 2010, more than 200 million people worldwide were believed to be living with lower extremity PAD.

References:

  1. Fowkes FG, Rudan D, Rudan I, et al. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet. 2013;19;382(9901):1329-1340.
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What is the standard diagnostic testing device for patients with suspected lower extremity PAD?

The diagnosis of lower extremity PAD can be greatly improved with the measurement of the resting ankle-brachial index (ABI), which is now a standard component of the initial evaluation in a patient suspected of having lower extremity PAD.

References:

  1. Tendera M, Aboyans V, Bartelink M-L, et al. ESC guidelines on the diagnosis and treatment of peripheral artery diseases. Eur Heart J. 2011;32:2851-2906.
  2. 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):S5-67.
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Compared to monovascular disease, the risk of stroke in patients with polyvascular disease that included lower extremity PAD has been shown to increase by approximately what percentage?

The REACH registry showed that even in treated patients, polyvascular disease that included lower extremity PAD increased the risk of MI by 20–40%, the risk of death due to CAD events by 2- to 6-fold, and the risk of stroke by approximately 40% relative to monovascular disease.

References:

  1. Grenon SM, Vittinghoff E, Owensw C, et al. Peripheral artery disease and risk of cardiovascular events in patients with coronary artery disease: Insights from the Heart and Soul Study. Vasc Med. 2013;18(4):176-184.
  2. 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) ACC/AHA PAD guidelines. Circulation. 2006;113:e463–e654.

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1/3

In the REACH registry study, approximately what percentage of patients with established PAD were not receiving at least 1 antiplatelet agent at the time of study?

A key finding was that patients with PAD were less likely to receive guideline-recommended therapies than patients with CAD (Figure 20). Notably, nearly 20% of patients with established PAD were not receiving at least 1 antiplatelet agent at the time of study (2003–2004).

References:

  1. Bhatt DL, Steg PG, Ohman EM, Hirsch AT, et al; REACH Registry Investigators. International prevalence, recognition, and treatment of cardiovascular risk factors in outpatients with atherothrombosis. JAMA. 2006;295(2):180-189.
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Of the following risk factors associated with lower extremity PAD, which carries the highest risk?

All of these factors confer a risk for developing lower extremity PAD, although a history of other cardiovascular (CV) disease appears to carry the highest risk. Being a current or former smoker also places patients at high risk.

References:

  1. Fowkes FG, Rudan D, Rudan I, et al. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet. 2013;19;382(9901):1329-1340.
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The majority of patients present with what type of PAD?

Approximately 20–50% of patients present with asymptomatic PAD, 30–40% with atypical leg pain, 10–35% with intermittent claudication, and 1–3% with critical limb ischemia.

References:

  1. 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):S5-67.

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1/3

Lower extremity PAD impairs functionality and quality of life in symptomatic patients only.

Lower extremity PAD impairs functionality and quality of life, even among people who do not report leg symptoms.

References:

  1. Roger VL, Go AS, Lloyd-Jones DM, et al; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2012 update: a report from the American Heart Association. Circulation. 2012;125(1):e2-e220.
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Which of the following is considered the primary goal of PAD management in patients with intermittent claudication?

Although all four are overall goals of lower extremity PAD management, the primary goal in the management of patients with intermittent claudication is to reduce the risk of morbidity and mortality.

References:

  1. Creager MA, Libby P. Chapter 58. Peripheral artery diseases. In: Mann DL, zips DP, Libby P, Bonow RO, eds. Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine, 10th edition. Saunders, an imprint of Elsevier. 2015;pp1312-1335.
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Guideline-recommended pharmacologic treatment for vascular protection in patients with carotid artery stenosis includes which therapies? Select one.

For both asymptomatic and symptomatic patients with CAS, the ESC guidelines state that all patients should be treated with long-term antiplatelet therapy and statins.

References:

  1. Tendera M, Aboyans V, Bartelink M-L, et al. ESC guidelines on the diagnosis and treatment of peripheral artery diseases. Eur Heart J. 2011;32:2851-2906.

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A PATIENT'S JOURNEY

Over 120 million people are estimated to have peripheral artery disease worldwide,1 yet it remains both under-diagnosed and under-treated. Here, we take a look at a fictional patient – Paul – to better understand the symptoms and the long-term outcomes of this disease.

By the help of the arrows, navigate through important stations of Paul’s future life. Click/tap on a station to get detailed infos!

45
Asymptomatic peripheral artery disease
51
Intermittent claudication
52
Health check
54
Critical limb ischaemia
Primary prevention of cardiovascular events
55
Difficulty maintaining lifestyle changes
58
Myocardial infarction
Secondary prevention of cardiovascular events
59
Continuing vascular protection

Age 45: Asymptomatic peripheral artery disease 45

A cigarette smoker since his mid-teens, Paul struggles to find time to exercise and by his mid-forties he is moderately overweight and has type II diabetes – a condition he manages with metformin. Unknown to Paul, by this time he has already developed several lipid plaques in his peripheral arteries, which partially restrict blood flow to his lower limbs.

Did you know?

Over half of patients with peripheral artery disease are completely asymptomatic2

Age 51: Intermittent claudication 51

Paul begins to experience occasional aching in his calf muscles when he walks longer distances – a symptom termed intermittent claudication. He attributes this to his age, so he makes more journeys by car and doesn’t see a doctor.

Did you know?

In one study, one-third of ambulatory patients with ‘asymptomatic’ peripheral artery disease developed symptoms when performing a 6-minute walk test,4 suggesting that their lack of symptoms in their everyday lives might be due to inactivity

Age 52: Health check 52

Because of his weight and diabetes, Paul is identified by his GP as having an elevated cardiovascular risk profile and is invited for a routine health check. A blood test reveals that he has high cholesterol levels, so he is prescribed a statin and advised to change his diet and stop smoking. However, his GP does not routinely offer diagnostic testing for peripheral artery disease and Paul doesn’t think to mention his difficulty in walking long distances.

Did you know?

Current guidelines from the European Society for Cardiology and the European Society for Vascular Surgery do not include a suggestion for systematic screening for asymptomatic peripheral artery disease unless the patient has documented disease in another vascular bed5

Age 54: Critical limb ischaemia 54

Two years later, and still a heavy smoker, Paul notices that an ulcer on his ankle has not gone away for some weeks. His GP identifies the ulcer as gangrenous and refers him to a vascular specialist, who diagnoses him with critical limb ischaemia. Paul undergoes a revascularization procedure to restore blood flow to his foot, without which amputation would have been required.

Did you know?

Patients undergoing revascularization for critical limb ischaemia are at particularly high risk of a vascular event in the first month after revascularization; within 30 days of surgery, nearly 1 in 12 patients will die or experience a stroke or myocardial infarction6

Age 54: Primary prevention of cardiovascular events 54

After surgery, Paul is prescribed two types of antiplatelet therapy (aspirin and clopidogrel) to reduce his risk of stroke or myocardial infarction. After a month, he is advised to stop taking aspirin but to continue taking clopidogrel alongside his cholesterol-lowering and diabetes medications.

Did you know?

Almost one-fifth of patients with peripheral artery disease in the multinational REACH registry were not receiving any antithrombotic therapy despite guideline recommendations7

Age 55: Difficulty maintaining lifestyle changes 55

Paul stopped smoking after the revascularization surgery, but less than a year later he thinks his condition is stable and begins smoking again. He has also continued to gain weight due to his lack of mobility, and is now categorized as obese.

Did you know?

Two-fifths of patients with peripheral artery disease are not adherent to at least one recommended secondary prevention therapy after 1 year of follow-up.8 Studies have suggested that improving patient education, actively involving patients in their treatment decisions and avoiding the prescription of numerous medications and behavioural changes in a single visit may all contribute to improving adherence to long-term therapies9

Age 58: Myocardial infarction 58

Four years after his revascularization, Paul is rushed to hospital with severe chest pain – a suspected myocardial infarction. An angiogram reveals widespread atherosclerosis of his coronary arteries, termed coronary artery disease, which requires another revascularization procedure to restore blood flow to the heart.

Did you know?

Over 60% of patients with peripheral artery disease also have atherosclerosis in the arteries of the heart, the brain or both7

Age 58: Secondary prevention of cardiovascular events 58

Paul’s symptomatic peripheral and coronary artery disease place him at very high risk of further cardiovascular events. On hospital discharge, he is again prescribed two antiplatelet agents, this time aspirin and ticagrelor, together with continuing statin therapy, metformin for his diabetes and antihypertensive agents to manage his high blood pressure. Like other patients after a major cardiac event, Paul is again given guidance on lifestyle changes including smoking cessation and dietary advice.

Did you know?

Patients with concomitant coronary and peripheral artery disease have an 81% higher incidence of stroke, myocardial infarction or death from cardiovascular causes over 1 year than patients with peripheral artery disease alone10

Age 59: Continuing vascular protection 59

Cardiovascular risk is highest in the first year after a vascular event, so 1 year after his heart attack Paul’s doctor recommends he stops taking ticagrelor. However, Paul and other patients like him are at a lifelong, continued risk of major adverse cardiac events. Paul will continue to take aspirin to reduce this risk, but newer antithrombotic therapy regimens and combinations remain the subject of research to improve the outcomes for this patient population.

Did you know?

Despite the use of effective secondary prevention strategies, 5–10% of patients with cardiovascular disease have recurrent events each year11,12

Show References

Approval code: G.MKT.GM.XA.12.2017.2016

  1. GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017;390:1211–1259.
  2. 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.
  3. Criqui MH, Aboyans V. Epidemiology of peripheral artery disease. Circ Res 2015;116:1509–1526.
  4. 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.
  5. Aboyans V, Ricco JB, Bartelink MEL et al. 2017 ESC Guidelines on the diagnosis and treatment of peripheral arterial diseases, in collaboration with the European Society for Vascular Surgery (ESVS): document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries. Eur Heart J 2017: doi:10.1093/eurheartj/ehx095.
  1. Conte MS, Bandyk DF, Clowes AW et al. Risk factors, medical therapies and perioperative events in limb salvage surgery: observations from the PREVENT III multicenter trial. J Vasc Surg 2005;42:456–465.
  2. Bhatt DL, Steg PG, Ohman EM et al. International prevalence, recognition, and treatment of cardiovascular risk factors in outpatients with atherothrombosis. JAMA 2006;295:180–189.
  3. Kumbhani DJ, Steg PG, Cannon CP et al. Adherence to secondary prevention medications and four-year outcomes in outpatients with atherosclerosis. Am J Med 2013;126:693–700.
  4. Brown MT, Bussell JK. Medication adherence: WHO cares? Mayo Clin Proc 2011;86:304–314.
  5. Steg PG, Bhatt DL, Wilson PW et al. One-year cardiovascular event rates in outpatients with atherothrombosis. JAMA 2007;297:1197–1206.
  6. Bhatt DL, Eagle KA, Ohman EM et al. Comparative determinants of 4-year cardiovascular event rates in stable outpatients at risk of or with atherothrombosis. JAMA 2010;304:1350–1357.
  7. Eikelboom JW, Connolly SJ, Bosch J et al. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med 2017;377:1319–1330.

Vascular Protection in Patients with PAD: A Challenge

Better therapeutic options are required in patients with PAD for the prevention of long-term adverse vascular events

Vascular Protection in Patients with PAD: A Challenge 03:59

Evolving Management Strategies in PAD

Management strategies and unmet needs in peripheral artery disease

Evolving Management Strategies in PAD 03:34 min