Week 2: Cardiovascular Risk Flashcards
… is a progressive disease of the large arteries, caused by the local accumulation of lipids and fibrous elements together with inflammation.
Atherosclerosis
T or F
Atherosclerosis is largely “silent” in patients, until a rupture of a plaque occurs, or the total blockage of an artery affects tissues in its vicinity.
T
T or F
The exact causes of atherosclerosis are not clear
T
How is atherosclerosis thought to start?
With damage to the endothelium of an artery
How does plaque form in an artery?
- Damage to the endothelium of an artery
- Cholesterol molecules get trapped and oxidise
- Monocytes from the blood stream navigate to the area
- Stimulation from the oxidised cholesterol turns monocytes into macrophages
- Macrophages eat and digest the cholesterol
- The macrophages change into foam cells
- Foam cells accumulate to form plaque.
T or F
plaque development cannot occur over years as adverse affects will arise well before then
F
plaque development can occur over years
… cells cover the surface of inter-arterial plaque build up, creating a thick, fibrous cap.
smooth muscle
Inter-arterial plaque can be … (there is a thick and fibrous cap covering the deposited lipid pool), or … (plaque that may rupture)
stabilised
vulnerable
Name the three layers of the arteriole
tunica intima, tunica media, and tunica adventitia
T or F
Some people can have severe atherosclerosis with no symptoms
T
LDL-C is good/bad cholesterol whilst HDL-C is good/bad cholesterol
bad
good
T or F
Atherosclerosis is thought to be affected equally by both genetics and environment/lifestyle.
T
List some modifiable risk factors to developing atherosclerosis
Elevated LDL-C, reduced HDL-C, diabetes, cigarette smoking, obesity, physical inactivity and hypertension
Cholesterol can be obtained by the body via what two ways?
either a diet of animal tissues or synthesised endogenously by the liver.
T or F
Cholesterol is needed for the absorption of lipid-soluble vitamins from the GI tract.
T
Which lipoprotein has the most free cholesterol?
LDL
Which type of lipoprotein is the largest?
Chylomicrons
What function do high-density lipoproteins (HDL) perform in the body?
move surplus cholesterol back to the liver from tissues for storage or excretion
Low-density lipoproteins (LDL) are what is formed after VLDL lipoproteins have had their … removed.
triglycerides
Which type of lipoproteins are able to cross dysfunctional endothelium and contribute to foam cell formation?
LDLs
… are responsible for the transport of lipids from the intestinal absorption after eating, taking its contents to the tissues and liver
Chylomicrons
The right order of lipoproteins in terms of density from lowest to highest is…
chylomicrons – VLDL – IDL – LDL – HDL
Lipoproteins are composed of; An outer shell of …, core of fats including … and surface … molecules to help tissues recognise and take up the particles.
phospholipids
cholesterols
apoproteins
The surface of lipoproteins contains
hydrophilic/hydrophobic components while the core contains hydrophilic/hydrophobic components.
hydrophilic
hydrophobic
T or F
One of the functions of apolipoproteins is to mediate binding of lipoproteins to lipoprotein receptors.
T
Cholesterol and lipid from our food intake is absorbed from the … and transported in …
small intestine
chylomicrons
List some secondary causes of dyslipidaemia
A sedentary lifestyle
High intake of saturated fat, cholesterol and trans fats.
Cigarette smoking
Anabolic steroids
Some medications
Dyslipidaemia is usually primarily due to … causes
genetic
The primary goal of drug therapy in dyslipidaemia is the reduction of …
LDL-C
Match the pleiotropic effects to their corresponding benefits:
- Increased NO production
- Atherosclerotic plaque stabilisation
- Reduced platelet aggregability
a. Reduced likelihood of plaque rupture
b. Reduced risk of blood clot formation
c. Vasodilation
1c, 2a, 3b
Match the pleiotropic effects to their corresponding benefits:
- Reduction in vascular formation
- Down-regulation of AT1 receptor expression
- Reduction in VSMC migration
a. Decreased rate of plaque build-up
b. Reduced cytokines and signaling molecules driving inflammation
c. Decreased effects on Ang-II
1b, 2c, 3a
List some rare but serious concentration-dependent reactions to statin medications
Myopathy and rhabdomyolysis (breakdown of skeletal muscle sarcolemma, releasing muscle fibre contents (myoglobin) into the bloodstream, possibly leading to acute kidney injury).
Name some drug classes that can be prescribed for the treatment of dyslipidaemia.
Statins, fibrates, ezetimibe, bile-acid binding resins (in severe disease), bempedoic acid, monoclonal antibodies to PCSK9 and siRNA treatment of PCSK9
Bempedoic acid works by inhibiting … which is two steps upstream from …, which statins inhibit
adenosine triphosphate citrate lyase (ACL)
HMG-CoA reductase
Match the drug class with its primary mechanism of action:
- Statins
- Fibrates
- Bempedoic acid
- Small interfering RNA coding for PCSK9
a. Inhibition of ACL
b. Inhibition of HMG-CoA reductase
c. Inhibits synthesis of PCKS9
d. Increasing expression of lipoprotein lipase
1b, 2d, 3a, 4c,
What seven factors are used to estimate CVD risk?
Smoking, elevated blood pressure, dyslipidaemia, diabetes, increasing age, male sex and left ventricular hypertrophy.
What is the mechanism of action for statins?
Reduce endogenous cholesterol by competitively antagonising HMG-CoA reductase -> Reduces melvalonate -> reducing cholesterol synthesis
What is the rate limiting step in cholesterol biosynthesis?
The enzyme HMG-CoA reductase
What is the mechanism of action for fibrates?
Agonise PPAR-alpha -> Transcription of LP lipase and major HDL lipoproteins -> Large decrease in circulating VLDL/triglycerides with a moderate decrease in LDL and increase in HDL
What is the mechanism of action for ezetimibe?
Inhibits cholesterol absorption in the ileum, causing an increased need for cholesterol. In response tissues will increase their LDL receptor lvls which will lead to an increase in LDL excretion from the body via bile
What is the mechanism of action for bempedoic acid?
Inhibits adenosine triphosphate citrate lyase (ACL), an enzyme two steps upstream of HMG-CoA reductase. By reducing the body’s ability to synthesise cholesterol, LDL-C in the bloodstream is more likely to be cleared due to an increased density of LDL receptors being expressed on tissues.
What is the mechanism of action for monoclonal antibodies to PCK9?
PCSK9 is made by cells and plays a role in degrading LDL receptors. Blocking PCSK9 reduces the lysosomal degradation of LDL receptors. This mechanism thus increases the number of LDL receptors present.
