Atherosclerosis

Question 1

What is atherosclerosis?

Answer 1

Infiltration of LDLs into the sub endothelial region

Question 2

What is cholesterol?

Answer 2

Essential structural component allowing cells to function without a cell wall

Question 3

What are TGs?

Answer 3

3 fatty acids connected by a glycerol backbone
FA oxidized for energy by tissues except brain

Question 4

What are chylomicrons?

Answer 4

Large lipoproteins containing +++ triglyceride (80-95%)
Major vehicle to carry dietary fat and cholesterol

Question 5

What is the role of chylomicrons?

Answer 5

Source of TG fro adipose tissue and muscle (cardiac and skeletal)
Source of TG and cholesterol for liver to produce VLDL

Question 6

What is LDL?

Answer 6

Bad cholesterol
Main carrier of cholesterol in blood (60-70%)

Question 7

What is HDL?

Answer 7

Good cholesterol
Formed by remodeling of chylomicrons or by VLDL catabolism (in liver)
Main role - reverse cholesterol transport

Question 8

When does LDL become dangerous?

Answer 8

Oxidized LDL appears to elicit an immune response
Monocytes are attracted to the tissue and are activated into macrophages

Question 9

What appears to be a key trigger to the atherosclerotic process?

Answer 9

Oxidation of LDL
It provokes an inflammatory response

Question 10

How can you prevent oxidation?

Answer 10

Antioxidants

Question 11

Who should be treated with statins?

Answer 11

Individuals with a “statin-indicated condition”
- clinical atherosclerosis, abdominal aortic aneurysm, diabetes, CKD, LDL > 5mmol/L
Individuals with a high 10-year risk for CV disease
Individuals with a high “lifetime risk” can be considered

Question 12

What is the main effect of statins?

Answer 12

On LDL levels in the blood

Question 13

MOA of statins

Answer 13

Inhibit an enzyme in the pathway for intracellular synthesis of cholesterol

Question 14

What us a high intensity statin?

Answer 14

Any statin that drops LDL by >50% (atorvastatin 80mg & rosuvastatin 20mg or 40mg)

Question 15

What other effects do statins have on plasma lipids?

Answer 15

HDL increase avg 5-10%
TG decrease up to 30%

Question 16

What is the time for maximal effect of a statin?

Answer 16

6-12 weeks

Question 17

What medications can be added on?

Answer 17

First line add in therapy: ezetimibe
Second line: PCSK9 inhibitor (more expensive)
Alternative first line: bile acid sequestrants (BAS) - less tolerable

Question 18

When would we add combo therapy?

Answer 18

When statin doses are maxed out
Tolerability issues (cannot increase statin anymore)

Question 19

What is a common AE of statins?

Answer 19

GI discomfort, fatigue

Question 20

What are uncommon AE of statins?

Answer 20

Rhabdomyolysis - muscle effects
Diabetes
Cognitive impairment

Question 21

What are the muscle concerns with statins?

Answer 21

10-30% report statin muscle side effects
Myalgia/muscle aches, stiffness and cramps, weakness, severe pain

Question 22

What interaction does atorvastatin have?

Answer 22

Grapefruit since it is a substrate and inhibitor of CYP3A4