Next Lesson - Cellular Adaptations
Core
Atherosclerosis is a condition affecting large and medium-sized arteries. It involves the formation of atherosclerotic plaques within the tunica intima (the innermost layer of the artery wall) of these arteries. These plaques often form at places where flow of blood is more turbulent, for example at branching points of arteries. Most plaques are asymptomatic (they cause no symptoms). However, if a plaque causes severe narrowing of the artery, it can lead to ischaemic damage (damage from too little blood supply).
Atherosclerosis commonly affects:
- Abdominal aorta
- Coronary arteries
- Carotid arteries
- Cerebral arteries (the arteries supplying the brain)
- Arteries in the leg
Risk Factors for Plaque Formation
Risk factors for atherosclerosis can be defined as modifiable (can be changed, such as smoking) and non-modifiable (cannot be changed, such as age):
Table - The risk factors for atherosclerosis
SimpleMed original by Dr. Emily Smith
The most important risk factor for atherosclerosis is hypercholesterolaemia - raised serum cholesterol. Three visible signs can point to hypercholesterolaemia. Corneal arcus is a white, grey or blue ring around the edge of the cornea (the clear front surface of the eye), which points to raised cholesterol mainly in people under about 50. Tendon xanthoma is a lump of cholesterol in a tendon. Xanthelasma is a yellowish patch of cholesterol on the eyelids. It is a weaker sign, because only about half of adults with xanthelasma have abnormal lipid levels (blood fat levels). Each sign is a deposit of cholesterol in the tissue.
Image - Corneal arcus: a deposition of lipid in the outer edges of the cornea forming a white ring
Creative commons source by Afrodriguezg [CC BY 3.0 (https://creativecommons.org/licenses/by/3.0)]
Image - Tendon xanthoma: deposition of lipid in tendons which forms lumps under the skin
Creative commons source by Kumar et al. (2008) [CC BY 3.0 (https://creativecommons.org/licenses/by/3.0)]
Image - Eyelid xanthelasma: symmetrical deposition of cholesterol in the skin around the eyelids
Creative commons source by Oleg Tymofii [CC BY 3.0 (https://creativecommons.org/licenses/by/3.0)]
Formation of the atherosclerotic plaque first involves chronic insult (long-term injury) to the arterial wall, for example by hypertension or hyperglycaemia (high blood glucose). This causes damage or dysfunction of the endothelium (the thin layer of cells lining the inside of the artery). The artery wall then makes a response to the damage: low-density lipoprotein (LDL, the cholesterol-carrying particle) builds up in the wall and inflammation follows, as shown in the diagram below.
Diagram - The steps involved in the formation of an atherosclerotic plaque
SimpleMed original by Dr. Emily Smith
Diagram - A labelled cross section of an atherosclerotic plaque. The plaque has blocked (occluded) a large proportion of the lumen (the channel inside the artery), reducing blood flow through the artery. Inside, the plaque is full of atheroma (the fatty material) made up of lipid, foam cells (white blood cells swollen with fat) and inflammatory cells.
SimpleMed Original by Dr. Emily Smith
Fatty Streak
- Early change in the formation of an atherosclerotic plaque
- Flat lesion (area of abnormal tissue) that doesn’t affect blood flow
- Consists of foam cells, smooth muscle cells and some extracellular lipids (fats lying outside the cells)
Simple Plaque
- Raised yellow or white lesion
- Starts to occlude the lumen of the artery
- Contains fibrosis (scar tissue), necrosis (dead tissue) and cholesterol crystals. It also extends into the tunica media (the muscular middle layer of the artery wall), and small new blood vessels grow into the plaque
Complicated Plaque
- This is progression of the disease that begins to cause symptoms. The different types of complicated plaques are explained below.
Complications of Atherosclerotic Plaques
Most plaques do not produce any symptoms. However, they can cause disease if they undergo certain processes.
- Progressive narrowing of lumen
- Stenosis (narrowing) that reduces the diameter of the lumen by about 70-80% leads to a significant reduction in blood flow.
- This can cause intermittent claudication (cramping leg pain on walking, relieved by rest) or angina (chest pain from reduced blood flow to the heart muscle) symptoms depending on the artery affected.
- Haemorrhage into the plaque
- This causes sudden expansion of the plaque, resulting in occlusion of the vessel or rupture of the plaque.
- Acute atherothrombotic occlusion (sudden blockage of an artery by a blood clot forming on a plaque)
- Rupture of the plaque exposes thrombogenic (clot-forming) substances to the blood stream, which causes a thrombus (blood clot) to form within a very short period of time.
- This can cause occlusion of the artery and lead to infarction of the supplied tissues.
- Embolisation
- This is another complication of atherothrombosis (clot formation on a plaque).
- Small fragments break off from the thrombus and become lodged distal to the plaque (further along the artery, downstream).
- This can result in small infarctions.
- Calcification
- Calcium builds up in the plaque and causes stiffness of the arterial walls.
- Increased stiffness can make the arteries more fragile and can alter haemodynamics (the way blood flows and pressure acts in the vessels).
- Although calcification can make arteries more fragile, calcified plaques are not the usual cause of haemorrhagic stroke (bleeding in the brain). Haemorrhagic stroke is usually due to rupture of small cerebral (brain) vessels or aneurysms.
- Aneurysm formation
- Local dilatations (widenings) of an artery due to a weakened arterial wall.
- An aneurysm is a persistent abnormal dilatation of an artery caused by weakening and degeneration of its wall. How it develops (its pathogenesis) is multifactorial, meaning there are several causes. Abdominal aortic aneurysms are commonly associated with atherosclerosis.
- Aneurysms commonly occur in the abdominal aorta.
- Large aneurysms can rupture and cause a massive haemorrhage. Plaque material can also embolise (break off and travel in the blood) to a distant site.
Diagram - An Abdominal Aortic Aneurysm (AAA). Large AAAs can be felt on palpation of the abdomen as large pulsatile masses (masses that throb with each heartbeat).
SimpleMed original by Dr. Emily Smith
Clinical Effects of Atherosclerosis
Narrowing and blockage of vessels from atherosclerosis can lead to several conditions. The heart, brain, kidneys, legs and bowel are areas which are commonly affected.
Ischaemic Heart Disease
These conditions are caused by reduced blood flow to cardiac tissue due to atherosclerotic plaques in the coronary arteries. They can show up as:
- Stable or unstable angina - temporary (transient) reduction of blood flow to the heart muscle (myocardial ischaemia), usually felt as chest pain. Stable angina is typically exertional (brought on by physical effort), whereas unstable angina can occur at rest.
- Myocardial infarction - necrosis of cardiac tissue due to occlusion of a coronary artery (heart attack)
- Heart failure - infarction leaves fibrosis (scar tissue) in the heart muscle, and scar tissue cannot contract, so the heart pumps less effectively
- Arrhythmias (abnormal heart rhythms) - fibrosis of the heart muscle can disrupt electrical pathways
- Sudden cardiac death
Cerebral Ischaemia
This is caused by a reduced blood supply to the brain. A sudden fall in supply can be due to atherosclerosis of a carotid or cerebral (brain) artery, thromboembolism or cardiac arrest. Thromboembolism is a blood clot, or a piece of one, that travels from elsewhere and blocks an artery. A gradual fall can be due to long-standing narrowing of the arteries. Reduced blood supply to the brain can lead to:
- Ischaemic stroke - cerebral infarction (death of brain tissue) caused by the occlusion (blockage) of a cerebral artery by thrombosis (a clot forming in the artery) or thromboembolism. About 86% of strokes are ischaemic. The rest are haemorrhagic, caused by bleeding in or around the brain.
- Transient ischaemic attack (TIA) - temporary (transient) neurological dysfunction due to cerebral ischaemia. The clinical definition is time-based: symptoms last from a few minutes to a few hours and, by definition, fully resolve within 24 hours. The newer tissue-based definition replaces the 24-hour limit with a different test: it requires that there is no evidence of infarction (tissue death).
- Vascular dementia - ischaemic damage and reduced blood flow to the brain causing dementia.
Mesenteric Ischaemia
This type of ischaemia is caused by a reduction in blood supply to the bowel. It can cause:
- Ischaemic colitis - inflammation and injury to the large bowel due to inadequate blood supply. This can result in acute ulceration and haemorrhage.
- Chronic mesenteric ischaemia - pain after eating, which often leads to a fear of eating and to weight loss.
- Bowel infarction - blockage (occlusion) of an artery supplying the intestines, causing the bowel tissue to die (infarction).
Peripheral Arterial Disease (also called peripheral vascular disease)
This group of conditions affects the lower limbs. It can present as:
- Intermittent claudication - cramping pain in the legs that is brought on by exercise and relieved by rest. It is caused by stenosis (narrowing) of the arteries to the legs.
- Leriche syndrome - atherosclerotic narrowing or blockage of the lower abdominal aorta and the iliac arteries (the arteries that carry blood from the aorta to the pelvis and legs). It classically causes three features. The first is cramping pain in the buttocks and legs on walking (claudication). The second is weak or absent femoral pulses (the pulses felt in the groin). The third is erectile dysfunction (difficulty getting or keeping an erection).
- Ischaemic rest pain - continuous pain in the lower limb at rest, caused by ischaemia. Rest pain with or without tissue loss (such as ulcers or gangrene, explained below) is called chronic limb-threatening ischaemia. It needs urgent referral to a vascular team (specialists in diseases of the blood vessels).
- Gangrene - loss of blood supply resulting in tissue death.
Conditions Affecting the Kidneys
- Hypertension - renal artery stenosis (narrowing of a kidney artery) lowers blood flow to the kidney (renal perfusion). The kidney then activates the renin-angiotensin-aldosterone system (RAAS), a hormone system that raises blood pressure throughout the body (systemic blood pressure).
- Renal failure - renal artery stenosis can cause chronic kidney disease (long-term loss of kidney function). It can also cause end stage renal failure, where the kidneys no longer work well enough to sustain life without dialysis (a machine that filters the blood in place of the kidneys) or a transplant.
Atherosclerosis doesn’t have any symptoms until the plaque becomes complicated. Therefore, prevention mechanisms are important. These include:
- Stop smoking or do not start
- Control hypertension
- Prevent obesity by a healthy diet and regular exercise
- Reduce alcohol intake
- Control diabetes mellitus
- Lower raised cholesterol through diet
- Statins (cholesterol-lowering medicines) are offered when the 10-year QRISK3 score is 10% or more. QRISK3 is a tool that estimates the chance of heart or blood vessel disease, such as a heart attack or stroke, over the next 10 years.
- Statins are also offered to people with chronic kidney disease (long-term loss of kidney function) whatever their score, and to some adults with type 1 diabetes.
If a plaque becomes complicated and produces symptoms, then intervention for patients can include:
- Drugs such as statins (which lower cholesterol) and antiplatelet drugs such as aspirin or clopidogrel (which make blood clots less likely to form). The choice depends on the condition: for example, clopidogrel may be recommended after an ischaemic stroke or TIA, and is recommended as an option in peripheral arterial disease.
- Thrombolysis (medicine that dissolves a blood clot). For an ischaemic stroke, the medicines used are alteplase or tenecteplase, given within 4.5 hours of the start of symptoms once a bleed in the brain has been ruled out. For a heart attack, thrombolysis is used when emergency angioplasty (opening the blocked artery with a balloon) cannot be done quickly enough.
- Thrombectomy (using a catheter, a thin tube, to pull a clot out of a blocked brain artery). In an ischaemic stroke caused by a blocked large artery at the front of the brain, it is offered as soon as possible and within 6 hours of the start of symptoms. Some people can have it up to 24 hours after they were last known to be well, if scans show brain tissue that can still be saved.
- Angioplasty (using a small balloon to stretch open a narrowed artery)
- Stents (short wire mesh tubes left in the artery to keep it open)
- Coronary artery bypass graft (CABG): surgery that uses a blood vessel from elsewhere in the body to go around a narrowed part of a coronary artery
Edited by: Dr. Bethany Turner
Reviewed by: Dr. Thomas Burnell and Dr. Marcus Judge
- 13698
