Hyperlipidaemia

Question 1

define hypercholesterolaemia

Answer 1

elevated levels of cholesterol

Question 2

what are the uses of cholesterol

Answer 2

• cell membranes (particularly nerve cells)
• steroids
• vitamin D

Question 3

define hypertriglyceridaemia

Answer 3

high levels of triglycerides

Question 4

what are the uses of triglycerides

Answer 4

• insulation and protection

- energy store

Question 5

where does cholesterol come from

Answer 5

comes from 2 sources:

1. body produces it in liver
2. food sources- meat, poultry, fish, eggs, butter, cheese

Question 6

describe why elevated levels of cholesterol are dangerous

Answer 6

1. breach damaged endothelium (damage due to sheer stress, diabetes, ageing and hypercholesterolaemia)
2. oxidised cholesterol then attracts monocytes in to the sub endothelium initiates the process of atherosclerosis

Question 7

give examples of sources of triglycerides

Answer 7

• alcohol, sugar, saturated and trans fats, high calorie foods, refined grains or starchy foods

Question 8

describe the process of absorption of triglycerides

Answer 8

1. fatty acids and monoglycerides are emulsified by bile salts to form micelles
2. fatty acids enter the epithelial cells and link to form triglycerides
3. triglycerides combine with proteins inside the Golgi body to form chylomicrons
4. chylomicrons enter the lacteal and are transported away from the intestine

Question 9

why are triglycerides bad for you

Answer 9

1. decrease HDL cholesterol
2. increase obesity
3. increase insulin resistance
4. increase blood coagulation

Question 10

describe the structure of low density lipoprotein

Answer 10

1. 1 x apoprotein molecule
2. 1500 cholesteryl ester molecules
3. surrounded by 800 phospholipid molecules
4. 500 cholesterol molecules

Question 11

what are apolipoproteins

Answer 11

1. protein particles formed in liver/intestine
2. > 9 types including Apo A-1, apo B, Apo E
   - Apo A 1, A2 linked to HDL and therefore protective against cardiovascular disease
   - Apo B-100 linked with LDL and therefore risk factor for CVD

Question 12

what is the role of Apo E

Answer 12

1. Apo E linked to VLDL- affects breakdown of cholesterol
   - E2 is good, protects against dementia and CVD
   - E3 is neutral
   - E4 is bad, linked to Alzheimers disease and CVD

Question 13

what are hyperlipidaemias classed as

Answer 13

1. either primary- familial hypercholesterolaemia
   - 5% of cases are familial (increased low density lipoproteins or lipoprotein lipase deficiency)
2. secondary to other diseases
   - diabetes mellitus (increased triglycerides/ decreased HDL)
   - alcoholism ( increased triglycerides and cholesterol)
   - chronic renal failure ( increased triglycerides and LDL)
   - hypothyroidism (increased LDL cholesterol)
3. or diet

Question 14

what is the current acceptable level of total cholesterol

Answer 14

less than 5.0mmol/l

Question 15

what is the current acceptable level of LDL cholesterol

Answer 15

less than 3.0mmol/l

Question 16

what is the current acceptable level of HDL cholesterol

Answer 16

greater than 1.0mmol/l

Question 17

what is the current acceptable level of triglycerides

Answer 17

less than 2.3mmol/l

Question 18

describe how diet can be altered as a treatment of hyperlipidaemias

Answer 18

1. soluble fibre in diet- oat bran, fruit and veg
2. soy proteins
3. stanol esters- inhibit cholesterol absorption
4. fish oils- reduce triglycerides
5. exercise- increase HDL

Question 19

what are the classes of drug treatment of hyperlipidaemias

Answer 19

1. primary prevention of CHD
2. secondary prevention of CHD
3. familial hypercholesterolaemia

Question 20

how is the ability to absorb cholesterol blocked

Answer 20

1. ion exchange resins- eg. cholestyramine, cholestipol
   - side effects: GIT problems, wind constipation, prevent absorption of fat soluble vitamins and drugs
2. ezetimibe

Question 21

what are statins and how do they work

Answer 21

1. hydroxy-3-methyl-glutaryl coenzyme A reductase (HMG-CoA) inhibitors
   - eg. simvastatin, atorvastatin, lovastatin
2. they work by increasing LDL receptor numbers on liver
3. main treatment for hypercholesterolaemia

Question 22

what are the benefits of statins

Answer 22

1. most effective cholesterol lowering drugs
2. decrease the incidence of MI/stroke in primary and secondary prevention
3. maybe of benefit even if LDL levels are normal
4. also increase HDLs and decrease C reactive protein

Question 23

what are the indications of bempedoic acid

Answer 23

primary hypercholesterolaemia or mixed dyslipidaemia in patients who have not responded adequately to other appropriate measures

Question 24

what are the side effects of bempedoic acid

Answer 24

anaemia, gout, hyperuricaemia, pain in extremity

Question 25

what are Proprotein convertase subtilisin-kexin type 9 (PCSK9)

Answer 25

1. plays pivotal role in LDL C metabolism
2. serine protease that degrades intracellular LDL R
3. less LDL R on surface
4. Less LDL C taken up by liver
5. inhibited by evolocumab and alirocumab

Question 26

give examples of fibrates and what are they used for

Answer 26

eg. fenofibrate, benzafibrate and ciprofibrate

- main treatment for people with only high plasma triglycerides or combined with statins in mixed hyperlipidaemias

Question 27

what is nicotinic acid and what is it used for

Answer 27

1. reduces lipolysis in fat cells
2. reduces synthesis of VLDLs
3. increases clearance of chylomicrons
4. used in combination with ion exchange resins
   - limited uses because it causes vasodilation

Question 28

what are w-3-acid ethyl esters and what are they used for

Answer 28

1. omega 3 marine triglycerides
2. relax endothelium, anti arrhythmic, antithrombotic
3. used to reduce triglycerides
4. side effects can include: belching and occasional nausea

Question 29

what vitamins are lipid soluble

Answer 29

A, D, E, K

Question 30

how do lipids and cholesterol travel around the body

Answer 30

as lipoproteins

Question 31

how do ion exchange resins reduce serum LDL cholesterol

Answer 31

1. bind bile acids and cause them to be passed out in the faeces
2. by binding bile acids, they decrease liver cholesterol
3. liver expresses LDL receptors
4. this pulls LDL out of the blood
5. decreases serum LDL cholesterol

Question 32

name the vitamins whose absorption will be inhibited by ion exchange resins and what is the potential consequence of this inhibition

Answer 32

1. vitamin A- deficiency can affect vision, the immune system and fertility
2. vitamin D- deficiency can affect calcium absorption and bone health
3. vitamin E- antioxidant and can help to control free radical damage
4. vitamin K- used for the production of clotting factors

Question 33

how do statins reduce LDL cholesterol

Answer 33

1. inhibit HMG CoA reductase
2. inhibit cholesterol production in liver
3. liver expresses LDL receptors
4. This pulls LDL cholesterol from bloodstream
5. decreases serum LDL cholesterol

Question 34

why do you have to take some statins at night but not others

Answer 34

1. cholesterol synthesis mainly occurs at night
2. statins with a short half life need to be taken at night so they are around at high enough concs to inhibit synthesis (simvastatin)
3. statins with long half life can be taken at any time during the day (atorvastatin)

Question 35

how do fibrates reduce serum triglycerides

Answer 35

1. activate specific transcription factors belonging to the nuclear hormone receptor superfamily, termed PPARs
2. they increase transcription of Apo A1 and A2 major proteins of HDL particles and so can decrease LDL cholesterol
3. also increases the expression of lipoprotein lipase which can increase uptake of TGs into muscle and fat cells