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The Basics

What is atherosclerosis?

Atherosclerosis is a chronic, systemic condition that results in the build-up of plaques in the arteries.1-3 Depending on which arteries are affected, this may manifest as:

  • Coronary artery disease – atherosclerosis in the arteries of the heart
  • Peripheral artery disease – atherosclerosis in the extremities
  • Cerebrovascular disease – atherosclerosis in the cerebral arteries
Manifestations of atherosclerosis.

Manifestations of atherosclerosis.

Atherosclerosis can manifest as coronary artery disease, peripheral artery disease or cerebrovascular disease

The formation of plaques occurs over several decades, starting as thickening of the inner surface layer of an artery exposed to the blood (the intima) and progressing to an advanced lesion called a fibroatheroma.3,4


Plaques may lead to acute events by narrowing the arteries and the formation of blood clots.5


For more detailed information on the progression of atherosclerosis, please see the Understanding arterial thrombosis section.

Plaque formation in atherosclerosis

Plaque formation in atherosclerosis.

Formation of arterial plaques

Why does atherosclerosis cause strokes and heart attacks?

Events such as heart attacks and stroke are caused by a sudden restriction in arterial blood flow to the heart or brain, respectively.2

The majority of these acute ischaemic events occur when, due to rupture or erosion, an atherosclerotic plaque releases material that promotes blood clotting.1,2 This leads to the formation of a large blood clot known as a thrombus.1

As well as causing heart attacks and strokes, atherosclerosis can also occur in the lower limbs, where it is known as peripheral artery disease and can lead to acute limb ischaemia, a condition characterized by a sudden decrease in limb perfusion; this can lead to pain and, in some cases, amputation.8,9 For more detailed information on the progression of atherosclerosis, please see the Understanding arterial thrombosis section.

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Peripherial Artery Disease: causes and consequences

An overview of atherosclerosis, its causes and treatment options.
The basics of atherosclerosis

Who is at risk of atherosclerosis?

Traditionally, the major risk factors for atherosclerosis were considered to be the following:3,8

  • Elevated cholesterol
  • Hypertension
  • Smoking
  • Diabetes
  • Male gender
  • Increasing age


More recently, however, new risk factors have been identified, including:9

  • A family history of early onset cardiovascular disease
  • Moderate or severe chronic kidney disease
  • Psychosocial risk factors (such as low socioeconomic status, depression and stress)
  • Inflammatory and autoimmune disease (such as rheumatoid arthritis)
Risk factors for atherosclerosis

Risk factors for atherosclerosis.

Non-modifiable and modifiable risk factors for atherosclerosis

When is atherosclerosis most serious?

There are several factors that can increase the risk of serious acute events in patients with atherosclerotic disease. The most significant risk factor is polyvascular disease, where atherosclerotic plaques develop in multiple arterial beds at the same time (e.g. in both the coronary arteries and the arteries of the lower limb).10 Notably, 24.7% of patients with coronary artery disease and 61.5% with peripheral artery disease have concomitant disease in another arterial bed.11

Polyvascular disease occurs frequently in patients with atherosclerosis

Polyvascular disease occurs frequently in patients with atherosclerosis.

Data showing the occurrence of concomitant atherosclerosis

Patients with polyvascular disease have an especially high risk of events such as heart attack and stroke, and prognosis worsens as more arterial beds are affected.12,13

Certain co-morbidities can also increase the risk of acute events in patients with atherosclerosis and, in many cases, these overlap with the risk factors that increase the risk of developing atherosclerosis.8,10 Previous ischaemic events, diabetes and heart failure have all been shown to increase the risk of events, and patients with any of these conditions may require careful management.10

How is atherosclerosis diagnosed?

The symptoms associated with atherosclerosis depend on the arteries affected.


Coronary artery disease (CAD) most commonly manifests as discomfort or pain in the chest or shortness of breath. In patients with suspected CAD, the European Society of Cardiology (ESC) guidelines recommend that the first stage of diagnosis is to establish the probability of CAD based on clinical history, basic testing and assessment of left ventricular function. Once a diagnosis has been confirmed, an appropriate therapy will be determined based on the progression stage of the cardiovascular disease.14

Peripheral artery disease (PAD) is suspected in patients with pain in the lower legs, non-healing of wounds or an absent or abnormal pulse in the lower extremities. In these patients, ankle–brachial index (the ratio of blood pressure in a leg to that in the arm) is recommended to objectively confirm PAD. Suspicion of PAD may also arise from clinical history alone.15

How is atherosclerosis treated?

Treatment of atherosclerosis focuses on providing symptomatic relief and reducing the risk of acute events. Where necessary, most patients will be encouraged to adopt certain lifestyle modifications including smoking cessation, adoption of a healthy diet and increased exercise.14,16

By making these lifestyle changes, patients can address several risk factors associated with increased risk of acute events; however, drug therapy may also be required. For example, patients with atherosclerosis may receive an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to reduce blood pressure, a statin to address lipid levels and antithrombotic therapy to reduce the risk of clots. In some patients with atherosclerosis, surgical interventions may be required.14,16

For more detailed information on specific treatment approaches for coronary artery disease and peripheral artery disease, please see the Managing atherosclerosis section.

Effective vascular protection can limit the risks associated with atherosclerosis

Effective vascular protection can limit the risks associated with atherosclerosis.

Overview of management of atherosclerosis

  • Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature 2011;473:317–325. Return to content
  • Drouet L. Atherothrombosis as a systemic disease. Cerebrovasc Dis 2002;13 Suppl 1:1–6. Return to content
  • Bentzon JF, Otsuka F, Virmani R, Falk E. Mechanisms of plaque formation and rupture. Circ Res 2014;114:1852–1866. Return to content
  • Yahagi K, Kolodgie FD, Otsuka F et al. Pathophysiology of native coronary, vein graft, and in-stent atherosclerosis. Nat Rev Cardiol 2016;13:79–98. Return to content
  • Insull W, Jr. The pathology of atherosclerosis: plaque development and plaque responses to medical treatment. Am J Med 2009;122:S3–S14. Return to content
  • Bradberry JC. Peripheral arterial disease: pathophysiology, risk factors, and role of antithrombotic therapy. J Am Pharm Assoc (2003) 2004;44:S37–S45. Return to content
  • Acar RD, Sahin M, Kirma C. One of the most urgent vascular circumstances: acute limb ischemia. SAGE Open Med 2013;1:2050312113516110. Return to content
  • Mozaffarian D, Wilson PW, Kannel WB. Beyond established and novel risk factors: lifestyle risk factors for cardiovascular disease. Circulation 2008;117:3031–3038. Return to content
  • Piepoli MF, Hoes AW, Agewall S et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: the sixth joint task force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of 10 societies and by invited experts) developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J 2016;37:2315–2381. Return to content
  • 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. Return to content
  • 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. Return to content
  • Steg PG, Bhatt DL, Wilson PW et al. One-year cardiovascular event rates in outpatients with atherothrombosis. JAMA 2007;297:1197–1206. Return to content
  • Subherwal S, Bhatt DL, Li S et al. Polyvascular disease and long-term cardiovascular outcomes in older patients with non-ST-segment-elevation myocardial infarction. Circ Cardiovasc Qual Outcomes 2012;5:541–549. Return to content
  • Knuuti J, Wijns W, Saraste A et al. 2019 ESC guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J 2020;41:407–477. Return to content
  • 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 2018;39:763–816. Return to content
  • Fihn SD, Gardin JM, Abrams J et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation 2012;126:e354–e471. Return to content

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