atherosclerosis

Question 1

lipoprotein particles and how measured

Answer 1

lipid carried in LDL and HDL LDL measured using apoprotein B, HDL using apoprotein A1

Question 2

reverse cholesterol transport

Answer 2

HDL can be converted into VLDL/LDL using CETP

Question 3

mechanism of atherosclerosis

Answer 3

starts with leaky endothelium, and more endothelial adhesion molecules due to inflammation- leads to leukocyte adhesion leukocytes enter into intima, T cells and platelets are activated, and foam cells form to from a fatty streak, which forms atheroma (core of extracellular lipid) plaque then formed- macrophages accumulate, leading to necrotic core (full of smooth muscle cells and dead macrophages), and fibrous cap plaque can then break down and form thrombus

Question 4

remnant lipids

Answer 4

when large lipid molecules like chylomicrons break down, it leaves remnants, which increase risk of atherosclerosis thus remnants are chylomicron remants, VLDL and IDL

Question 5

DIAGRAM vulnerable atherosclerotic plaque

Answer 5

stable plaque has narrower blood vessel lumen, but large division between lipid and necrotic core, so less dangerous vulnerable has larger lumen, but thin division, so prognosis worse as more likely to break down

Question 6

plaque rupture

Answer 6

when ruptured, it activates TF, coagulation factors etc= thrombus

Question 7

LDL- danger and what worsens its effects

Answer 7

10% increase= 20% CHD risk increase worsened by low HDL, hypertension, diabetes, smoking

Question 8

how HDL is lowered

Answer 8

smoking, obesity, lack of exercise

Question 9

association between total cholesterol and mortality

Answer 9

correlation, but different in different countries, suggesting other factors eg Mediterranean diet influence this

Question 10

how statins work

Answer 10

inhibit HMG CoA= mevalonic acid due to HMG-CoA reductase in liver cells liver upregulates LDL receptors, so more LDL in blood taken up by liver, so less in blood

Question 11

problem with statins

Answer 11

RULE OF 6- if you double dose, only leads to 6% further reduction

Question 12

relative reduction in risk of CHD due to statins

Answer 12

about 30%

Question 13

fibrates= mechanism and problem

Answer 13

activates PPAR alpha receptors, the thiazolidinediones used in diabetes= less FA/triglycerides however not many trials done

Question 14

nicotinic acid

Answer 14

should lower LDL/increase HDL, but no studies show it, so only used in minority

Question 15

ezetimide- mechanism and how used

Answer 15

inhibits absorption of cholesterol- often used in combination with statin to counteract problem with statin

Question 16

CETP inhibitors

Answer 16

should increase HDL/lower LDL, but not really in use

Question 17

PCSK9 inhibitor- how given, and what it solves

Answer 17

this inhibits LDL receptors, so less LDL removed from blood thus inhibitor often given with statin