ATHEROSCLEROSIS


DEFINITION
Lit. "Gruel-hardening".
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INCIDENCE
Incidence
Everybody.
28% of deaths in this country due to IHD, 10% to CVAs.
Rapidly increasing.

Risk Factors
(Framingham and MRFIT studies)
Personal
Age.
Males (increased risk up to 55 yrs).
Stress (only because of lifestyle associations).

Familial
Familial hyperlipidaemia.
FHx clustering positive.
50% of risk is probably related to unknown familial genetic factors.

Environmental
Smoking.
High fat diet (hyperlipidaemia).
Alcohol (J-shaped curve).
Sedentary lifestyle.

Diseases
Hypertension.
DM.
Hyperlipidaemias.
Haemostasis factors.
Gout.

Drugs
OCP (weak).
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AETIOLOGY
Vascular Degeneration.

Pathogenesis
There are many theories as to the cause of atherosclerosis.
But not known for sure.

Insudation Theory of Virchow
Says that primary problem is the accumulation of lipids into the vessel wall".

Thrombosis theory of Rokitansky
Says that primary problem is thrombosis at sites of damaged endothelium, occurring as a result of platelet adhesion.
Thrombi are then incorporated into the wall.

Modern Understanding
Now thought maybe a combination of the two.
Poorly understood endothelial cell dysfunction, together with additional haemostatic abnormalities.
Leads to fibrocellular proliferation and poorly understood lipid deposition in the media of the arteries.

Other Theories
There are also "design fault", "infectious", "smooth muscle cell proliferation" theories, but these are less favoured.
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BIOLOGICAL BEHAVIOUR

Pathophysiology
Develops over decades.
Normally LDL lipid particles flow between the arterial lumen and wall.
First insult prob occurs when LDL becomes oxidised in the wall.
Monocytes are attracted and traverse the endothelium.
These ingest the toxic oxidised LDL.
They are transformed into macrophage 'foam cells'.
And often then die, releasing enzymes and mediators.
The enzymes cause local tissue destruction and attract more macrophages.
The cycle continues...
Fibrocellular proliferation and monoclonal smooth muscle cell proliferation occurs in and around the lesion.
The lesions enlarge.

Symptoms develop when the artery is too narrow to allow nutrients to supply demand.
Does not occur until at least 40% of the circumference is covered.
At first the artery remodels (widens) to compensate.
Collateral vessels may develop.

Pathology

Stages:


Fatty streaks
Evident in young people.
Focal, eccentric intra-luminal narrowings or plaques containing foam cells and intracellular lipids.
At first sporadically covering parts of the affected arteries, the plaques slowly become more numerous and widespread.

Transitional plaques
Contain foam cells, intracellular lipids and extracellular lipids.

Advanced fibrolipid plaques
Extracellular lipid core, smooth muscle and foam cells.

Locations:
Certain sites are predisposed:
Big elastic arteries - aorta, carotid, iliacs.
Also large/ medium muscular arteries (e.g. coronary and popliteal).
Especially at bifurcations.
Most often the arteries to the heart, brain, kidneys, lower limbs, and small intestine are affected.
Curiously, seemingly similar vessels are relatively free, eg internal thoracics.

Stability
Atherosclerotic plaques can be:

Stable
Have a thick fibrous cap which covers the small highly thrombogenic lipid core.

Vulnerable / unstable

Have a thin fibrous cap and extensive lipid core.
Prone to rupture.
Often at times of increased adrenergic drive.
When ruptured, thrombogenic contents are exposed.
Platelets settle, followed by a red cell and fibrin based thrombus.
Embolism may follow, or haemorrhage into the plaque.

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MANIFESTATIONS
Depends on the location, extent, and type / state of plaque.

Clinical scenarios include:
Coronary artery disease.
- Stable plaque -> chronic angina.
- Unstable plaque -> acute coronary syndromes.
Cerebrovascular disease.
Peripheral vascular disease.
Mesenteric vascular disease.
Renal vascular disease.
Aneurism.
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INVESTIGATIONS
See individual notes.
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MANAGEMENT

Prevention/Conservative
Don't smoke.
Normal BP.
Target weight (especially male centripetal fat).
Eat a Mediterranean diet (especially tomatoes).
Exercise.
Moderate alcohol consumption at most.
Lower total LDL, increase HDL.
Change family history.
Etc.
Pts must be encouraged to take as much control of their risk factors as possible.

Drugs
Lipid lowering agents.
Eg statins, fibrates.
Hypertension control.
Strict glycaemic control in diabetics.
Prevent thrombotic complications using antiplatelet drugs.
Treat complications.

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