Hyperlipidaemia and its treatment Flashcards
(35 cards)
What is hyperlipidaemia a major risk factor for?
serious cardiovascular disorders such as heart attack, stroke and angina
Where does the blood supply for the heart come from?
The coronary blood supply?
What is coronary artery disease and what is heart disease?
- Coronary artery disease is the build up of the fatty plaque (angina and heart attack)
- Heart disease is the process of having the fatty plaque
What is angina and what is it the warning sign for?
- heart is temporarily deprived of oxygen
- warning sign for a heart attack
What is a heart attack and what does it lead to?
The heart is deprived of oxygen. This compromises the heart’s ability to pump properly and leads to heart failure
What are dysrhythmias?
interrupted heart rhythm
What are the numbers associated with hyperlipidaemia?
- 1.5 million have had a heart attack (11% die within 30 days) – (1965 70% fatal)
- 2.3 million people have coronary heart disease
- 2 million people have angina
- 920, 000 people have heart failure
- Heart attack and angina: £6.7 billion cost to UK economy
How do you prevent coronary heart disease?
- Primary prevention: stopping it happening
- Secondary prevention: stop it recurring or worsening (after angina, heart attack or stroke)
- Lifestyle interventions
- Drugs
What do lipoproteins do and what are they composed of?
- Transport lipids in plasma
- Composed of:
- Lipids (triglyceride or cholesterol esters) PLUS
- Phospholipids, cholesterol, proteins
- Phospholipid outer layer and Apo lipid proteins
- Cholesterol and triglycerides in core (hydrophobic core)
What do lipoproteins vary in?
- Lipid content
- Size and type of protein, DENSITY:
HDL (high)
LDL (low)
VLDL (very low)
Chylomicrons (lowest density)
Describe the production and absorption of cholesterol
- Hepatocyte synthesises cholesterol
- Cholesterol used by liver to make bile acids, these are secreted into GI tract, they act as a detergent, Bile acids recycled back to liver
- Dietary fats taken up by GI tract into chylomicrons
- Chylomicrons transport fats to the tissue
- Tissue takes up fatty acid after breaking down fats using lipoprotein lipase
- What’s left is termed chylomicron remanent, taken up by the liver where it delivers cholesterol
- Liver then produces VLDL (releases into circulation) and HDL
- VLDL delivers more fat to the tissues and in doing that is converted into LDL
- LDL delivers cholesterol to the tissues (cholesterol uptake)
- HDL takes up cholesterol from the tissues and delivers it to VLDL (cholesterol recycling)
- LDL can be recognised by liver and taken up
What are LDL and BDL known as and why?
- LDL and VDL known as bad cholesterol
Involved in formation of fatty streaks
Inhibit fibrinolysis (prevent fibrin breakdown)
Activate platelets (increase aggregation)
Increased risk of atherosclerosis
What do high levels of LDL lead to?
- Stenosis (narrowing) caused by fatty plaques in the vessel wall leads to: Ischaemia (angina) - Plaque ruptures, leads to: Thrombosis, leads to: Heart attack, stroke
What does HDL do?
- Increases fibrinolysis (increase fibrin degradation)
- Increase prostacyclin formation (decrease aggregation)
- High HDL/LDL – lower risk of atherosclerosis
Give features of hyperlipidaemias
- Number of different forms
- High level of lipids in blood
- Different disturbances in LDL, VLDL, cholesterol etc
- Treated differently
What is familial hypercholesterolaemia, who has it and how can it be treated?
- Defect in LDL receptor or ApoB protein
- Autosomal dominant
- 1:500 in UK heterozygous
CVD by age 30-40 - 1:1000000 homozygous
Severe CVD in childhood - Treated using statins but other drugs may be added too
What are the main components of an atherosclerotic plaque?
the nuclei of foam cells
What did foam cells start off as and what has this led us to recognise?
Foam cells started off as macrophages. This has led us to recognise that atherosclerosis is a chronic inflammatory condition instead of a lipid storage disease
How does a macrophage turn into a foam cell and then a fatty plaque?
- Hyperlipidaemia: excess LDL in blood circulation enters the intima of a blood vessel
- Immune cells enter the intima: Monocytes migrate into the intima and transform to macrophages
- Macrophages transform into foam cells: macrophages take up oxidised LDL and transform to foam cells. Foam cells release cytokines and other growth factors that recruit smooth muscle cells
- Formation of fatty plaque: the foam cells attach to the endothelium and form the fatty streak. Migrating smooth muscle cells thicken the streak into a stable plaque
What is the aim with lipid lowering drugs?
- Reduce LDL/VLDL
- Increase HDL
Give an example of a statin?
Atorvastatin
What do statins do?
- Competitively inhibit HMG-CoA reductase, rate limiting enzyme in production of cholesterol (similar in structure)
- Reduces liver production of cholesterol
- Lowered cholesterol leads to more LDL receptors (increased removal of LDL from plasma)
- Also increase HDL and lower triglycerides
Give a summary of initial steps in the synthesis of cholesterol
- Acetyl-coenzyme A leads to:
- HMG-CoA (using HMGCoA reductase) leads to:
- Mevalonate, leads to:
- Cholesterol
What are problems with statins?
- Cause Myositis (muscle inflammation)
- Rhabdomyolysis (muscle breakdown) – myoglobin released from muscles, ends up in urine and leads to kidney failure (renal failure)
- Altered liver function tests
