Dyslipidaemia Flashcards
1
Q
Name? Is?
A
- white circular line around the cornea
arcus senilis
corneal arcus
2
Q
Corneal Arcus is present in
A
> 50% age 50
3
Q
Corneal Arcus is a sign of dyslipidaemia in patients aged
A
<45 years old
4
Q
Cholesterol (3):
- synthesised by
- especially
- is an integral part of
A
- synthesised by all animal cells
- especially by the liver
- integral part of the cell membranes
5
Q
Cholesterol functional group is
A
OH
alcohol
6
Q
Cholesterol is a member of the steroid class of molecules.
True or False?
A
True
7
Q
What type of relationship between atherosclerotic disease and cholesterol levels?
A
Linear relationship
8
Q
Triglyceride structure:
A
- glycerol backbone
- three fatty acids
9
Q
Lipoproteins are miscible with water.
True or False?
A
False
Fats are immiscible with water
10
Q
Lipoproteins have varying quantities of (3):
A
- cholesterol
- triglyceride
- apolipoproteins
11
Q
Fats are carried in the blood as a part of
A
lipoprotein molecules
12
Q
Lipoprotein
A
13
Q
Core of lipoprotein:
A
- cholesterol (esters)
- triglyceride
14
Q
Surface of the lipoprotein:
A
- cholesterol (free)
- apolipoproteins
- phospholipid
15
Q
VLDL
A
very low density lipoproteins
16
Q
Relationship between the size and density of a lipoprotein?
A
The larger a lipoprotein the lower the density
17
Q
Which type of lipoproteins are of the lowest density and the largest size?
A
chylomicrons
18
Q
Lipoprotein subtypes
A
19
Q
Basic cholesterol pathway ***
A
20
Q
What step of cholesterol synthesis is targeted most by drugs?
A
- rate limiting step
- HMG-CoA Reductase
21
Q
Exogenous Pathway for lipoproteins: Label diagram and give a description:
A
- gut to liver (fat transport)
- dietary fats transported from the gut in
chylomicrons - triglyceride component broken down the
by LIPOPROTEIN LIPASE in capillary
endothelium - remnants transported to the liver
- liver secretes bile acids and some
cholesterol into the gut
22
Q
Endogenous pathway for lipoproteins: Label diagram and give a description:
A
- liver to peripheral tissues
- Liver produces VLDL and LDL
- Triglyceride component of VLDL broken
down by Lipoprotein Lipase in the
endothelium - IDL transported to the liver and converted
to LDL - LDL binds to LDL receptors on peripheral
tissues
23
Q
Reverse Pathway for lipoproteins: Label diagram and give a description:
A
- peripheral tissues to liver
- some free cholesterol in tissues is taken up
into HDL - HDL is transported to the liver
24
Q
Ideal Lipid Profile:
A
- low LDL
- high HDL
- low level of total lipoprotein/ HDL
- low triglyceride level
25
Typical Reference Ranges for Lipids:
- total cholesterol <5mmol/L
- LDL cholesterol <3mmol/L
- HDL cholesterol > 1.5 mmol/L
- Total/HDL ratio <3.5
- Triglyceride 0.5-2.0 mmol/L
26
Causes of Secondary Dyslipidaemia:
- diabetes mellitus
- hypothyroidism
- chronic kidney disease
- chronic liver disease
- obesity
- smoking
- medications: thiazide diuretics,
bendoflumethiazide
- excess alcohol (increased triglyceride
levels)
27
Primary Dyslipidaemia:
- abnormal lipoprotein structure
- abnormal lipoprotein receptors
NOT DUE TO INCREASED INTAKE OR SYNTHESIS
28
Excess alcohol consumption increases what molecule levels resulting in dyslipidaemia?
triglyceride
29
4 types of lipoproteins and description:
- Chylomicron: deliver triglycerides and
cholesterol from the intestines to the liver
- VLDL: deliver triglycerides from the liver to
the tissues
- LDL: deliver cholesterol from the liver to
the tissues (bad cholesterol)
- HDL: deliver cholesterol from the tissues to
the liver
30
Fredickson Classification table
31
Familial Hypercholesterolaemia Type IIa:
- due to
- dominant or recessive?
- causes?
- what % of population?
- consider diagnosis if:
- due to specific mutations that lead to the
absence/low levels of LDL receptors
- autosomal dominant
- causes severe atherosclerosis and may see
IHD in young adults especially men
- 0.5% of the population
- very high LDL cholesterol (>5.ommol/L,
even at birth)
- consider diagnosis if total cholesterol
>7.5mmol/L
- triglyceride levels near normal
32
Familial Combined Hyperlipidaemia Type IIb:
- mutations
- dominant/ recessive
- commonly involves
- affects what % of the population
- lipid profile
- commonly associated with
- accounts for what % of premature IHD
cases
- polygenetic condition
- autosomal dominant
- mostly involve overproduction of
apolipoprotein B-100***
- affects 10% of the population
- moderately high levels of cholesterol and
triglycerides
- LDL, VLDL and triglycerides are all elevated
- insulin resistance and obesity (metabolic
syndrome)
- accounts for 20% of premature IHD cases
33
Familial Hypertriglyceridaemia Type IV:
- mutation
- affects what % of the population
- lipid profile
- associated with
- risk of
- association with IHD
- multiple genetic defects, polygenic
- 1% of the population
- elevated triglycerides (>5.0mmol/L),
relatively normal cholesterol, HDL often
low
- insulin resistance and obesity (metabolic
syndrome)
- risk of acute pancreatitis (if TG level >10),
due to pancreatic capillary obstruction by
lipoprotein accumulation
- not strongly associated with IHD
34
Familial Hyperchylomicronaemia Type I:
- due to
- dominant or recessive
- lipid profile
- key feature
- risk
- due to a deficiency of lipoprotein lipase
- autosomal recessive
- very high triglycerides, normal cholesterol
- spun blood is creamy ***
- pancreatitis more likely than IHD
35
Familial dysbetalipoproteinemia Type III:
- due to
- dominant or recessive
- hence
- hence
- lipid profile
- increased risk of
- clinical sign
- due to a deficiency of Apolipoprotein E
- autosomal recessive
- poor lipoprotein clearance by the liver
- chylomicrons and IDK remain in blood
- modest elevations of cholesterol and
triglycerides
- increased risk of IHD
- palmar xanthomas
36
If a patient has very high LDL cholesterol (8mmol/L) and total cholesterol 10mmol/L and triglyceride levels are near normal, which type of dyslipidaemia?
Familial Hypercholesterolaemia Type IIa
37
A patient has familial hypertriglyceridaemia type IV. What is the main risk with this condition, when and why would this risk occur?
- risk of acute pancreatitis
- occurs if triglyceride levels >10mmol/L
- accumulation of lipoproteins in pancreatic
capillaries leads to obstruction
38
what type of hyperlipidaemia to consider when a patient has palmar xanthomas?
type III
dysbetalipoproteinemia
39
Xanthomas =
lipid deposits in the skin
generally eyes
40
What clinical sign is this?
Xanthesmata
Lipid deposits around the eyes
Usually lipid laden macrophages
41
Tendon xanthomas
lipid deposits
attached to extensor surface tendons
eg: achilles tendon
42
what clinical sign is this?
tendon xanthomas
43
What clinical sign is this? Specific to which type of dyslipidaemia?
palmar xanthomas
lipid deposits in the skin creases of the hands
specific to familial dysbetalipoproteinemia
44
What clinical sign is this? Where is it seen? Patients complain of? Condition?
- eruptive xanthomas
- reddish bumps that appear suddenly on
elbows, forearms, trunk, legs
- seen in severe hypertriglyceridaemia
45
Core Drug: Atorvastatin:
- type of drug
- used for
- mechanism
- hence (4)
- statins
- first line for most patients with elevated
cholesterol
- inhibits HMG-CoA Reductase ***
- reduces cholesterol production by the liver
- lowers LDL, total cholesterol and
triglyceride levels
- increases HDL levels
46
Core Drug: Simvastatin:
- type of drug
- used for
- mechanism
- hence (4)
- statins
- first line for most patients with elevated
cholesterol
- inhibits HMG-CoA Reductase ***
- reduces cholesterol production by the liver
- lowers LDL, total cholesterol and
triglyceride levels
- increases HDL levels
47
Management of hyperlipidaemia:
- lifestyle
- statins
48
Management of hyperlipidaemia: Lifestyle:
- aerobic exercise
- smoking cessation
- alcohol moderation
- weight loss for obese patients
- diet: portion control, limit carbs, oily fish
(omega 3 fatty acids)
49
Why do we treat hyperlipidaemia with statins?
- to prevent development/progression of
atherosclerosis
- reduces all cause mortality (reduction in
death from established arterial disease
patients hence wont take drug and die
from a side effect of statin)
50
Statins work so well because
- reduces LDL, increases HDL
- less inflammation
- alters plaque components
51
Statins reduce all cause mortality in a wide range of patients:
- MI or stroke
- CABG (coronary artery bypass grafting)
- PCI (percutaneous coronary intervention)
52
Do we use statins in patients with hyperlipidaemia who have never had a vascular event?
Yes
Primary prevention
53
Statins for primary prevention advantages and disadvantages
adv: reduces risk of adverse events in higher
risk patients
disadv: medicating well patients
side effects: myalgia (muscle pains) ***
Rhabdomyolysis (dangerous
muscle breakdown)
Arthralgia (joint pains)
Liver dysfunction
54
Statins side effects:
- myalgia (muscle pains)
- Rhabdomyolysis (dangerous muscle
breakdown)
- Arthralgia (joint pains)
- Liver dysfunction
55
What is the risk assessment tool used for hyperlipidaemia/ cardiovascular?
Q-risk
based on multivariate analysis from the Framingham Heart Study
56
***NICE: statins for primary prevention:
- if 10 year risk of cardiovascular disease >
10%
- Q-risk score
- check lipids after 3 months of statins
- aim for LDL reduction of >40% on statins
- ***no other drugs are reccomended for
primary prevention based on estimated
risk
57
First line drugs for patients with very high triglyceride levels?
Fibrates
58
Core Drug: Bezafibrate:
- used
- mechanism
- hence
- side effects
- first line for patients with very high
triglyceride levels
- activate lipoprotein lipase (endothelium),
strips triglyceride out of chylomicrons and
VLDL
- lower triglyceride, LDL
- increases HDL
- side effects: myalgia/rhabdomyolysis, GI
disturbances
59
Is bezafibrate more potent than atorvastatin?
No
atorvastatin is more potent
60
Bile salt sequestrants:
- cholestryamine
- absorbs bile salts that are used to absorb
lipids and are then lost in stool
- prevents re-uptake of bile salts in the gut
- reduces fat absorption
- cholesterol diverted to bile salt production
in the liver
- mild effect only
- reduces LDL but increases triglycerides
- side effects: GI disturbances
61
Is cholestyramine effective?
Mildly
62
Core Drug: Ezetimibe:
- mechanism
- hence
- lipid profile
- effective?
- commonly used
- side effects
- selectively inhibits the absorption of
cholesterol by the small intestine
- does not alter the absorption of fat soluble
vitamins
- only lowers LDL
- mild effect
- commonly used as an add on to statins
- side effects: GI disturbances
63
is cholestyramine more selective than ezetimibe?
no
ezetimibe more selective
64
When is ezetimibe used alone?
Rarely
if a patient really cant tolerate statins
65
Omega-3 fatty acids and hyperlipidaemia:
- how
- does what
- side effects
- atlantic salmon, tuna, anchovies
- tablets
- reduce VLDL synthesis by the liver
- reduce triglyceride > cholesterol
- side effects: GI disturbances
66
Niacin=nicotonic acid= vitamin B3 and hyperlipidaemia:
- how
- does what
- used for
- side effect
- inhibits lipase enzymes in adipose tissues
- mild reduction in LDL/TG, marked increase
in HDL
- used for patients with very high Lp-a levels
- side effect: facial flushing
67
Evolocumab:
- mechanism
- used for
- side effects
- PCSK9 inhibitor (monoclonal antibody)
- PCSK9 is a circulating enzyme which binds
to the LDL receptor and reduces LDL
clearance
- hence drug inhibits enzyme so increases
LDL clearance hence reducing LDL levels,
and triglyceride levels also increases HDL
levels
- very powerful, expensive and used for
familial hypercholesterolemia and patients
who fail to reach target goals on statins
alone
- side effects: cough/flu-like symptoms
68
why do PCSK9 inhibitors produce side effects like cough/flu?
- all drugs of this class are monoclonal
antibodies
- cough and flu like symptoms are partly due
to antibodies produced
