4.1.1 Hyperlipidaemia and Statins

Question 1

Where does cholesterol come from?

Answer 1

Most synthesised in body
25% from diet

Question 2

What is cholesterol used for?

Answer 2

Membrane integrity
Precursor of steroid hormones (lipophilic)
Bile acids
Vitamin D

Question 3

Why is LDL more susceptible to oxidation?

Answer 3

Longer half life than other cholesterol

Question 4

Why is LDL particularly bad?

Answer 4

Susceptible to oxidation at damaged endothelium ROS contributes to endothelial dysfunction, increasing adherence of lipid rich deposits and foam cells formed, leads to atheromatous plaques

Question 5

Why is HDL good cholesterol?

Answer 5

HDL carrier of cholesterol away from circulation to tissues that need it and to the liver for bile production

Question 6

Why is raised cholesterol bad?

Answer 6

Associated with increased risk of CHD

Question 7

How is cholesterol measured?

Answer 7

Measured as
Non-HDL cholesterol
and HDL cholesterol in mmol/L

Question 8

Why is reducing cholesterol important?

Answer 8

Modiable risk factor for CVD
10% reduction affords 15% reduction in 10 year CHD mortality and 11% reduction in total mortality

Question 9

How is treatment determined?

Answer 9

Total CVD risk
Adherence
Lifestyle changes

Question 10

Why are high cholesterol levels not treated in the same way?

Answer 10

Different forms of hypercholesterolaemia, e.g. familial hyperlipidaemia has a different target focus

Question 11

What other risk factors increase the risk of suffering from a significant CV event?

Answer 11

(Typically measured of happening within the next 10 years)

Raised SBP
Raised HDL-C
Smoking
Diabtes
LVH

Question 12

When can fatty streak onset begin?

Answer 12

Can have very early onset

Question 13

What is the mechanism of action of statins?

Answer 13

Competitive inhibition of HMG-CoA reductase

Reduced concentration of cholesterol in the cell, stimulates synthesis of LDL receptors

Increased LDL receptors on the apical membrane, promoting LDL uptake from blood

Low intracellular cholesterol decreases VLDL secretion

Question 14

What additional benefits do statins have?

Answer 14

• Improved vascular endothelial function - ↑NO, VEGF, ↓endothelin
• Stabilisation of atherosclerotic plaque - ↓SMC proliferation ↑collagen
• Improved haemostasis - ↓plasma fibrinogen, platelet aggregation, ↑fibrinolysis
• Anti-inflammatory - ↓proliferation of inflammatory cells into plaque, plasma CRP, adhesion
  molecules and cytokines
• Antioxidant - ↓superoxide formation
  All contribute to reduction in CVD risk

Question 15

What are two examples of statins?

Answer 15

Atorvastatin
Simvastatin

Question 16

How are statins activated?

Answer 16

Simvastain and atorvastatin are both prodrugs, activated by first pass metabolism

Simvastatin- t1/2 2h
Atorvastatin- t1/2 24h

Question 17

Adverse effects of statins

Answer 17

GI disruption
Nausea and headache
Myalgia-diffuse muscle pain, dose related
Rare- rhabdomyolysis
Increased liver enzymes

Question 18

Why do statins cause rhabdomyolysis?

Answer 18

Increases creatine kinase x5

Question 19

When should you not take statins?

Answer 19

Renal or hepatic impairment
Pregnancy
Breastfeeding

Question 20

Important drug interactions of statins

Answer 20

CYP 3A4 important for statin metabolism

Amiodarone
Diltiazem
Macrolides- increase [statin] plasma

Amlodipine also increases [plasma] statin

Question 21

What should be considered while taking other drugs with statins?

Answer 21

May be appropriate to withhold statins short-term while taking other agents

Question 22

Why can grapefruit and citrus fruits inhibit CYP3A4?

Answer 22

Furanocoumarins which inhibit CYP3A4 activity

Question 23

Are all statins equal?

Answer 23

No, dose dependant reduction in LDL-C

Question 24

Why was cerivastatin withdrawn?

Answer 24

Caused deaths due to rhabdomyolysis and renal failure

Question 25

What are the NICE guidelines for offering statins?

Answer 25

Primary prevention- 20mg atorvastatin once daily if 10 year CVD risk is >10% using QRISK

Secondary prevention- 80mg atorvastatin once daily, if major CV event, amended according to adverse reactions in CKD-20mg

Question 26

What is done before prescribing statins?

Answer 26

Full lipid profile, HDL and non-HDL + trigylcerides

Question 27

What is the aim of statin treatment?

Answer 27

Broadly >40% reduction in non HDL-C at three months

Question 28

Why is simivastatin taken at night?

Answer 28

Short half life, so taken at night as circadian rhythm of LDL receptor synthesis/activity increases at night, so statin will be more effective

Question 29

What is the nocebo effect?

Answer 29

If you are told about potential adverse effects of a drug you are more likely to report experiencing them

Question 30

What statin nocebo effect had an increased number of reports?

Answer 30

Myalgia, people getting placebo reported myalgia