Hyperlipidaemia Flashcards
define hypercholesterolaemia
elevated levels of cholesterol
what are the uses of cholesterol
- cell membranes (particularly nerve cells)
- steroids
- vitamin D
define hypertriglyceridaemia
high levels of triglycerides
what are the uses of triglycerides
- insulation and protection
- energy store
where does cholesterol come from
comes from 2 sources:
- body produces it in liver
- food sources- meat, poultry, fish, eggs, butter, cheese
describe why elevated levels of cholesterol are dangerous
- breach damaged endothelium (damage due to sheer stress, diabetes, ageing and hypercholesterolaemia)
- oxidised cholesterol then attracts monocytes in to the sub endothelium initiates the process of atherosclerosis
give examples of sources of triglycerides
- alcohol, sugar, saturated and trans fats, high calorie foods, refined grains or starchy foods
describe the process of absorption of triglycerides
- fatty acids and monoglycerides are emulsified by bile salts to form micelles
- fatty acids enter the epithelial cells and link to form triglycerides
- triglycerides combine with proteins inside the Golgi body to form chylomicrons
- chylomicrons enter the lacteal and are transported away from the intestine
why are triglycerides bad for you
- decrease HDL cholesterol
- increase obesity
- increase insulin resistance
- increase blood coagulation
describe the structure of low density lipoprotein
- 1 x apoprotein molecule
- 1500 cholesteryl ester molecules
- surrounded by 800 phospholipid molecules
- 500 cholesterol molecules
what are apolipoproteins
- protein particles formed in liver/intestine
- > 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
what is the role of Apo E
- 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
what are hyperlipidaemias classed as
- either primary- familial hypercholesterolaemia
- 5% of cases are familial (increased low density lipoproteins or lipoprotein lipase deficiency) - 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) - or diet
what is the current acceptable level of total cholesterol
less than 5.0mmol/l
what is the current acceptable level of LDL cholesterol
less than 3.0mmol/l
what is the current acceptable level of HDL cholesterol
greater than 1.0mmol/l
what is the current acceptable level of triglycerides
less than 2.3mmol/l
describe how diet can be altered as a treatment of hyperlipidaemias
- soluble fibre in diet- oat bran, fruit and veg
- soy proteins
- stanol esters- inhibit cholesterol absorption
- fish oils- reduce triglycerides
- exercise- increase HDL
what are the classes of drug treatment of hyperlipidaemias
- primary prevention of CHD
- secondary prevention of CHD
- familial hypercholesterolaemia
how is the ability to absorb cholesterol blocked
- ion exchange resins- eg. cholestyramine, cholestipol
- side effects: GIT problems, wind constipation, prevent absorption of fat soluble vitamins and drugs - ezetimibe
what are statins and how do they work
- hydroxy-3-methyl-glutaryl coenzyme A reductase (HMG-CoA) inhibitors
- eg. simvastatin, atorvastatin, lovastatin - they work by increasing LDL receptor numbers on liver
- main treatment for hypercholesterolaemia
what are the benefits of statins
- most effective cholesterol lowering drugs
- decrease the incidence of MI/stroke in primary and secondary prevention
- maybe of benefit even if LDL levels are normal
- also increase HDLs and decrease C reactive protein
what are the indications of bempedoic acid
primary hypercholesterolaemia or mixed dyslipidaemia in patients who have not responded adequately to other appropriate measures
what are the side effects of bempedoic acid
anaemia, gout, hyperuricaemia, pain in extremity
what are Proprotein convertase subtilisin-kexin type 9 (PCSK9)
- plays pivotal role in LDL C metabolism
- serine protease that degrades intracellular LDL R
- less LDL R on surface
- Less LDL C taken up by liver
- inhibited by evolocumab and alirocumab
give examples of fibrates and what are they used for
eg. fenofibrate, benzafibrate and ciprofibrate
- main treatment for people with only high plasma triglycerides or combined with statins in mixed hyperlipidaemias
what is nicotinic acid and what is it used for
- reduces lipolysis in fat cells
- reduces synthesis of VLDLs
- increases clearance of chylomicrons
- used in combination with ion exchange resins
- limited uses because it causes vasodilation
what are w-3-acid ethyl esters and what are they used for
- omega 3 marine triglycerides
- relax endothelium, anti arrhythmic, antithrombotic
- used to reduce triglycerides
- side effects can include: belching and occasional nausea
what vitamins are lipid soluble
A, D, E, K
how do lipids and cholesterol travel around the body
as lipoproteins
how do ion exchange resins reduce serum LDL cholesterol
- bind bile acids and cause them to be passed out in the faeces
- by binding bile acids, they decrease liver cholesterol
- liver expresses LDL receptors
- this pulls LDL out of the blood
- decreases serum LDL cholesterol
name the vitamins whose absorption will be inhibited by ion exchange resins and what is the potential consequence of this inhibition
- vitamin A- deficiency can affect vision, the immune system and fertility
- vitamin D- deficiency can affect calcium absorption and bone health
- vitamin E- antioxidant and can help to control free radical damage
- vitamin K- used for the production of clotting factors
how do statins reduce LDL cholesterol
- inhibit HMG CoA reductase
- inhibit cholesterol production in liver
- liver expresses LDL receptors
- This pulls LDL cholesterol from bloodstream
- decreases serum LDL cholesterol
why do you have to take some statins at night but not others
- cholesterol synthesis mainly occurs at night
- statins with a short half life need to be taken at night so they are around at high enough concs to inhibit synthesis (simvastatin)
- statins with long half life can be taken at any time during the day (atorvastatin)
how do fibrates reduce serum triglycerides
- activate specific transcription factors belonging to the nuclear hormone receptor superfamily, termed PPARs
- they increase transcription of Apo A1 and A2 major proteins of HDL particles and so can decrease LDL cholesterol
- also increases the expression of lipoprotein lipase which can increase uptake of TGs into muscle and fat cells
