Atherosclerosis is a condition affecting large- and medium-sized arteries. It leads to the formation of atherosclerotic plaques which may eventually disrupt the blood flow to target organs.
The term comes from athere, the Greek word meaning gruel, referring to the deposition within the arterial walls, and sclerosis meaning hardening.
Atherosclerotic plaques form in the arterial wall. Previously, plaque formation was considered as a cholesterol storage disease. It is now regarded as a complex process involving interaction between the arterial wall and blood components, with inflammation playing a major role.
Plaque formation involves smooth muscle cells, leukocytes, and various mediators of inflammation and immunity, including cytokines and complement components. The first lesion seen is the fatty streak, which may develop into a plaque. Plaques have a lipid core and a fibrous cap.
Atherosclerotic plaques tend to occur in regions where vessels branch, curve or are irregular, where blood undergoes sudden changes in velocity and in direction of flow.
The traditional view of atherosclerosis was that plaques produce arterial narrowing, ie stenoses. The degree of stenosis was thought to be the main factor in diseases such as coronary artery disease. Recent understanding is that plaques grow outward rather than inward for much of their life history, so that substantial atherosclerosis can exist without producing stenosis. Hence, significant atherosclerosis may be silent clinically and invisible on angiograms. Stenoses are the 'tip of the iceberg' of atherosclerosis.
Plaque rupture and thrombosis
Acute clinical complications of atherosclerosis, such as acute coronary syndromes and ischaemic stroke, are usually due to rupture of a plaque, leading to thrombosis, with partial or complete obstruction of the artery.
Some plaques are more prone to rupture than others. 'High-risk' plaques are those with a thin cap and a large lipid core containing relatively more inflammatory cells and fewer smooth muscle cells. These 'vulnerable plaques' may be widespread and yet may not produce stenosis or ischaemia, so they are a hidden threat to health. This type of plaque tends to produce an acute problem (eg, acute coronary syndrome), whereas a more stable and stenotic plaque will produce a more chronic clinical picture (eg, stable angina).
These concepts of widespread and vulnerable plaques have implications for management, making it important to treat cardiovascular disease (CVD) not only with revascularisation procedures but with systemic treatments aimed at stabilising plaques and reducing thromboses.
Although atherosclerosis usually manifests in later life, its early phases are present in teenagers and young adults.
The clinical manifestations of atherosclerosis, such as CVD, are common in Western and urban populations and are an important and common cause of death and disease.
Many risk factors have been identified for atherosclerotic disease; the main ones are listed here. Note that most of the literature on this topic relates to the clinical manifestations of atherosclerosis, mainly rates of cardiovascular disease and coronary heart disease.
- Unhealthy blood cholesterol and lipoprotein levels: high total cholesterol, raised cholesterol:HDL level, raised LDL cholesterol, low HDL cholesterol and high triglyceride level.
- High blood pressure.
- Insulin resistance, diabetes.
- Overweight or obesity.
- Lack of physical activity.
- Unhealthy diet: high in saturated fats and trans fats, cholesterol, sodium and sugar.
- Older age.
- Family history of early CVD.
- High levels of blood CRP.
- Sleep apnoea.
- Atherosclerosis in its early stages is silent.
- The clinical presentation is usually with complications (see section below).
- Possible signs are:
- Xanthelasmata (from hyperlipidaemia).
- Bruits over large arteries (eg, carotid bruits).
- Aortic aneurysm.
- Poor peripheral pulses.
- Reduced ankle brachial index.
- Coronary heart disease:
- Cerebrovascular disease:
- Aortic aneurysm.
- Peripheral arterial disease:
- Acute limb ischaemia.
- Visceral ischaemia:
- Atheroembolic disease:
- This is the release of cholesterol crystals into arteries, usually following vascular surgery, catheterisation or anticoagulation.
- It may affect various organs - the kidneys (atheroembolic renal disease), skin, gastrointestinal system and brain.
Investigation of atherosclerosis itself (rather than its clinical manifestations) is not routine in clinical practice, but has been used as a research tool. Possible techniques include:
- Ultrasound measurement of carotid intima-media thickness using B-mode ultrasound - this has some limitations.
- Intravascular ultrasound - this can detect atherosclerotic plaques not visible on angiography; it may show up recent plaque disruption.
- High-resolution MRI.
- CT - multi-slice spiral CT or electron-beam CT to quantify coronary artery calcium.
Further reading and references
Otsuka F, Yasuda S, Noguchi T, et al; Pathology of coronary atherosclerosis and thrombosis. Cardiovasc Diagn Ther. 2016 Aug6(4):396-408. doi: 10.21037/cdt.2016.06.01.
Linton MF, Yancey PG, Davies SS, et al; The Role of Lipids and Lipoproteins in Atherosclerosis
Lu H, Daugherty A; Atherosclerosis. Arterioscler Thromb Vasc Biol. 2015 Mar35(3):485-91. doi: 10.1161/ATVBAHA.115.305380.
Lauer MS; Screening asymptomatic subjects for subclinical atherosclerosis: not so obvious. J Am Coll Cardiol. 2010 Jul 656(2):106-8. doi: 10.1016/j.jacc.2010.01.059.
Rafieian-Kopaei M, Setorki M, Doudi M, et al; Atherosclerosis: process, indicators, risk factors and new hopes. Int J Prev Med. 2014 Aug5(8):927-46.
Fowkes FG, Murray GD, Butcher I, et al; Ankle brachial index combined with Framingham Risk Score to predict JAMA. 2008 Jul 9300(2):197-208.
Scolari F, Ravani P; Atheroembolic renal disease. Lancet. 2010 May 8375(9726):1650-60. Epub 2010 Apr 8.
Toth PP; Subclinical atherosclerosis: what it is, what it means and what we can do about it. Int J Clin Pract. 2008 Aug62(8):1246-54. Epub 2008 Jun 28.
Finn AV, Kolodgie FD, Virmani R; Correlation between carotid intimal/medial thickness and atherosclerosis: a point of view from pathology. Arterioscler Thromb Vasc Biol. 2010 Feb30(2):177-81. Epub 2009 Aug 13.
Waugh N, Black C, Walker S, et al; The effectiveness and cost-effectiveness of computed tomography screening for coronary artery disease: systematic review. Health Technol Assess. 2006 Oct10(39):iii-iv, ix-x, 1-41.