Lipids and Cardiovascualr Disease Flashcards
What are lipids
Organic compounds which are poorly soluble in water but soluble in organic solvents.
What are the 5 categories of lipids
Steroids, fat-soluble lipids, phospholipids, sphingolipids and triglycerides.
What is the important lipid in cardiovascular disease
Cholesterol (which is a steroid precursor) and phospholipids
By what molecule is cholesterol carried around the body
Lipoproteins
What is ApoB
The protein component of lipoprotiens
How are cholesterol and triglycerides transported around the body
Via the circulation
What are the 5 types of lipoprotien
Chylomicrons, very low density lipoprotein (VLDL), low density lipoprotein (LDL), intermediate density lipoprotein (IDL) and high density lipoprotein (HDL)
What’s the biggest lipoprotein
Chylomicrons
In what organ are dietary lipids created
The small intestine
In what organ are endogenous lipids created
The liver
How do lipids get from the peripheral tissues back to the liver for hepatic excretion.
Reverse cholesterol transport.
What are the three main pathways for transport and metabolism of cholesterol
Endogenous, exogenous and reverse cholesterol transport.
What type of cholesterol is the exogenous pathway concerned with
Dietary cholesterol
What type of cholesterol is the endogenous pathway concerned with
Cholesterol made by the body in the liver
What is the role of the reverse cholesterol transport pathway
To carry cholesterol from the peripheral tissues back to the liver.
How does the exogenous pathway work
The exogenous lipids are broken down. Triglyceride is absorbed into the small intestine and LPL (lipoprotein lipase) is activated which breaks down triglycerides to produce glycerol and fatty acids. These are taken up by muscle and adipose tissue. The remnants are chylomicrons which are taken up by the liver.
What is the important enzyme in the exogenous pathway
Lipoprotein lipase (LPL)
What is the role of LPL
To break down chlyomicrons into triglyceride and fatty acids.
What happens in the endogenous pathway
VLDL is made. VLDL is attacked by LPL to release glycerol and fatty acids to be taken up by muscle and adipose tissue. As this happens VLDL is converted to IDL and then LDL.
In what form can cells use and metabolise cholesterol
LDL as most cells have LDL receptors
What should happen to excess cholesterol
It should be returned to the liver.
What is the role of HDL
To return cholesterol to the liver
What happens to the cholesterol when it is returned to the liver by HDL
It is stored or gotten rid of,
What does cholesterylester transfer protein (CETP) do
It disrupts the return of cholesterol back to the liver by HDL be transferring HDL to VLDL so that the endogenous pathway is carried out
What is the name of the enzyme which converts HDL to VLDL disrupting the reverse cholesterol transport pathway
The cholesterylester transfer protein (CETP)
What allows cholesterol to be carried in HDL
ABC-A1 transporter
What do apolipoproteins do
Determine the behaviour of lipoproteins
What type of apolipoprotein is present in chylomicrons
ApoB48
What type of apolipoprotein is present in IDL
ApoB100
What type of apolipoprotein is present in HDL
ApoA1
What type of cholesterol causes atherosclerosis
Non-HDL cholesterol
What is the effect of raised HDL cholesterol on rates of atherosclerosis
Raised HDL decreases the rate of atherosclerosis
What drugs are used in cardiovascular disease to reduce cholesterol
Statins
What leads to the formation of fatty streaks
Damage to the arterial wall and high concentrations of LDL.
What happens to LDL molecules before they become incorporated into foam cells
They are oxidised by oxygen free radicals
What is a fatty streak
The collection of foam cells in the arterial wall.
How does an atheromatous plaque form from a fatty streak
Smooth muscle cells from the medial layer of the blood vessel migrate into the intimal layer. Some foam cells undergo necrosis or apoptosis to leave extracellular cholesterol and a fibrous cap forms.
what happens if the lesion is more fibrous and contains less cholesterol
It is less likely to rupture and leads to reduced blood flow which creates stable angina if in the coronary arteries.
What is an inherited disorder of lipoprotein metabolism
Familial hypercholesterolaemia
What causes familial hypercholesterolaemia
A mutation in the LDL receptor which means LDL cannot be up-taken efficiently by cells in peripheral tissues so hangs around in the circulation
What happens to LDL that cannot be taken up by cells in familial hypercholesterolaemia
It is taken up by ,macrophages to create foam cells which enter the endothelium of blood vessel walls to create fatty streaks and eventually an atherosclerotic plaque.
What does familial hypercholesterolaemia lead to if left untreated
Premature CHD onset.
What is one of the tell-tale signs of familial hypercholesterolaemia
Stigmata of hyperlipodaemia
What is stigmata of hyperlipodaemia
Cholesterol tends to gather on tends and around the eyes and this can clearly be seen in patients when they present.
What can routine laboratory measurements tell you about lipids
The total cholesterol, HDL cholesterol and triglycerides. LDL cholesterol has to be calculated, it is not measured.
What drugs are used to treat CVD
ACE-inhibitors, beta-blockers, aspirin, statins.
What are the roles of ACE-inhibitors and beta-blockers
To reduce post-MI mortality by reducing blood pressure.
What are the roles of aspirin and statins
To reduce CVD recurrence and mortality
What is recommended for primary prevention of CVD
Lifestyle changes including -
- reduce fat, carbohydrates and salt in the diet
- carry out aerobic exercise
- BMI between 20 and 25kg/m2
- reduce alcohol consumption
- quit smoking
How do you decide who to treat
Use the risk calculator as there are many factors which contribute to CVD. This gives % risk for CVD event in the next 10 years. In Scotland - treat those with 20% risk or more. In England - treat those with 10% risk or more (differing guidelines)
Which socioeconomic class are most affected by CVD
The least affluent.
What are three examples of lipid-lowering drugs
Statins, ezetimibe, fibrates
What is the mechanism of action of statins
They reduce LDL cholesterol by inhibiting the rate limiting step of cholesterol synthesis. Liver cells become deplete of LDL, making them want to uptake more LDL.
What is the mechanism of action of ezetimibe
It inhibits cholesterol absorption at the small intestine.
What is the mechanism of action of fibrates
Cause an increase in LPL activity leading to enhanced IDL and LDL uptake and reduced VLDL synthesis.
What is the name of the new lipid-lowering drugs
PCSK9-inhibitors
What is the mechanism of action of PCSK9-inhibitors
PCSK9 is crucial in cholesterol metabolism. it targets LDL receptors for destruction by lysosomes. If you inhibit this action, more LDL will be taken up by cells
What are the names of 2 PCSK9 inhibitors
Alirocumab and evolocumab
