Definition of atherosclerosis
Atehrosclerosis is characterised by fibrofatty plaques (atheromas) that form within the intima of arteries particularly the large elastic arteries (e.g. aorta) and large-medium sized muscular arteries (e.g. coronary, renal and popliteal arteries).
Atherosclerotic plaques can obstruct blood flow in a vessel, rupture leading to thrombosis and occlusion of teh vessel or weaken the media leading to an aneurysm formation.
Atherosclerosis may ultimately lead to:
- Ischaemic heart disease: angina pectoris, MI, chronic ischaemic heart disease, death.
- Cerebral infarction (stroke) and transient cerebral ischaemia
- Aortic aneurysm; and
- Peripheral vascular disease (intermittent cladication, gangrene)
Risk factors for developing atherosclerosis
Major non-modifiable risk factors
- Male/postmenopausal women
- Family history/genetic predisposition
Major modifiable/treatable/preventable risk factors include
- Cigarette smoking
- Poor diet
- Low physical activity
- High alcohol
- Chronic kidney disease
- Social isolation/depression
Other risk factors
- Inflammation (C-reactive protein is a serum marker)
- High blood homocysteine levels (can be treated with folate and vitamin B suppleents)
- Metabolic syndrome
- Lipoprotein(a) (an altered from of LDL that contains the apoliprotein B-100 portion of LDL linked to apolipoprotein A).
'Response to injury hypothesis' - chronic inflammatory response of the arterial wall initiated by injury to the endothelium.
- Chronic endothelial injury - endothelial dysfunction: increased pereability, leukocyte and platelet adhesion and thrombotic potential. This is caused by the endothelial cells response to injury caused by hyperlipidaemia, turbulence, HTN, smoking, homocystein, toxins, viruses immune reactions.
- Accumulation of lipoproteins: mainly LDL - high cholesterol content and its oxidised forms. LDL increases endothelial oxygen free radical production and oxidised LDL is ingested by macrophages. Oxidised LDL stimulates the release of growth factors and cytokines and chemokines by endothelial cells leading to increased monocyte recruitment. Oxidised LDL is cytotoxic to the endothelial cells and smooth muscle cells.
- Adhesion of blood monocytes: migration into intima and transformation into macrophages and foam cells (containing oxidised LDL). T cells interact with macrophages elaborating inflammatory cytokines which stimulate macrophages, endothelial cell and smooth muscle cells.
- Platelet adhesion and release of factors by activated platelets
- Smooth muscle cell recruitment: release of factors from activated platelets, macrophages or vascular cells that cause the migration of smooth muscle cells from the media into the intima. Smooth muscle cell proliferation and production of extracellular matrix (collagen and proteoglycans).
- Remodelling of the arterial wall: enhanced accumulation of lipids intracellularly (macrophages and smooth muscle cells) and extracellularly.
Macroscopic appearance of atheromas
Consist of a focal raised lesion consisting mainly of lipid with a firm fibrous cap. They are patchy and usually only involve a portion of the arterial wall. They are rarely circumferential. Early lesions consist of intimal smooth muscle proliferation and ECM deposition known as fatty streaks without the fibrous component. Older (mature) plaques may become calcified.
Microscopic features of atheromas
The atheromatous plaque consists of a raised intimal lesionw ith a superficial fibrous CT and SMC cap, a core of lipid (mainly cholesterol and cholesterol esters) with associated inflammatory and smooth muscle cells that lie beneath and to the side of the cap in what is called the 'shoulder region'.
There are three components to an atheromatous plaque:
- Cells: foam cells (lipid laden macrophages and SMCs), smooth muscle cells and chronic inflammatory cells.
- Extracellular matrix: collagen, elastic fibres and proteoglycans; and
- Lipid (intracellular and extracellular). Clefts of cholesterol crystals are also seen.
Complications in atheromas
- Haemorrhage into a plaque leading to an increase in size or rupture.
- Emboli from a ruptured plaque
- Thrombosis occurs on the damaged endothelium of a plaque leading to a further narrowing of the lumen or complete occlusion
Depends upon the vessels affected and the degree of occlusion or weakening of the vessel wall.
- An atherosclerotic stenosis of a vesse; (ie claudication and stable angina)
- Acute plaque change leading to thrombus formation and occlusion (ie unstable angina, acute MI, transient ischaemic attack)
- Haemorrhage into an atheroma
- +/- embolisation of cholesterol/thrombus
- Aneurysm formation (ie aorta)
Coronary artery disease manifestations
- Stable/unstable angina
Peripheral vascular disease manifestations
- Ischaemia of the lower limbs
A generic term for thickening and loss of elsticity of arterial walls ie 'hardening of arteries'.
It affects small arteries and arterioles - hyaline or hyperplastic - and is associated with luminal narrowing, associated with HTN and diabetes mellitus.
Patterns of hardening of vessels
Patterns of hardening include:
- Monckeberg medial calcific stenosis
Moncheberg medial calcific sclerosis
Calcific deposits in muscular arteries in persons older than 50, does not encroach on the vessel lumens.