Dr Usama AlAlami
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The coronary arteries are especially susceptible to the
formation of atheroma (plaques)
The reason for this is not fully understood.
The following risk factors contribute to the disease…
• Poor diet – high fat and low fruit & vegetables
• Lack of exercise
• Hypertension and diabetes
Atherosclerosis in the Coronary Arteries
A severely occluded coronary artery
There are various processes that cause the development
of an atheroma. The key ones are…
1. Accumulation of lipids
3. Damage by free radicals
Leucocytes are key players (transport lipids)
Diabetes and hypertension also exacerbate problem
• Cholesterol has been implicated in the development
and progression of cardiovascular disease.
• Ideally, cholesterol levels should be controlled by diet,
exercise and abstinence from harmful habits e.g.
• In reality, we often have to use statins
What do you remember about
• Cholesterol is a steroid lipid from animal fats in the
diet and can also be made in the liver.
• It is important for the structural stability of cell
membranes and also forms the raw material for the
manufacture of steroid hormones and vitamin D.
• It is also an important constituent of bile
• Cholesterol is transported in small spheres called
• There are two key types of lipoprotein…
• High density lipoprotein (HDL) that transports
cholesterol from the tissues to the liver
• Low density lipoprotein (LDL) that transports
cholesterol from the liver to tissue cells
(There are other types but these are the ones generally
encountered in blood tests)
How is cholesterol transported?
• The ratio between HDL and LDL is important,
generally, HDL should be high and LDL should be low.
• However, dietary cholesterol consumption is not the
sole determinant of serum lipid levels.
• Other lifestyle factors such as lack of exercise and
smoking can adversely affect the HDL : LDL ratio
• Sometimes a fall in blood cholesterol may provoke an
increase in hepatic cholesterol synthesis.
• This can result in elevated blood cholesterol despite a
reduction in dietary intake.
Recommended levels of cholesterol
Total cholesterol 5.2 mmol/L or lower
LDL (bad) cholesterol 3.5 mmol/L or lower
HDL (good) cholesterol 1.3 mmol/L or higher
*NHS Direct 2005
• Statins inhibit HMG CoA reductase* in the hepatocytes
• A key enzyme in the pathway that synthesises of cholesterol
• Inhibiting HMG CoA reductase reduces cholesterol production
• Low levels of cholesterol increase the expression of LDL
• This increases the uptake of LDL into the hepatocytes
• Cholesterol levels in the blood fall
*3-hydroxy-3-methylglutaryl coenzyme-A reductase
Cholesterol synthesis pathway
acetyl CoA + acetoacetyl CoA
(HMG CoA) Reaction
HMG CoA You do not need
to learn this
dimethyallyl geranyl pyrophosphate
squalene farnesyl pyrophosphate
squalene epoxide lanesterol
Summary of action of statins
Upregulation of LDL mevalonate
receptors pulls LDL
reaction inhibited by
into hepatocytes and
HMG CoA reductase
lowers serum LDL
cholesterol inhibitor (statin)
Examples - atorvastatin, fluvastatin, pravastatin,
rosuvastatin and simvastatin.
Contra-indicated in patients with liver disease,
pregnancy and breast feeding
Side effects – myositis (inflammation of muscles),
headache, GI disturbance etc.
Administered before bed as most cholesterol is
synthesised at night time
End of Presentation