Cardiovascular Risks

Question 1

List the 5 steps in the pathogenesis of atherosclerosis.

Answer 1

1. Fatty streak formation
2. Intermediate lesion formation
3. Atheroma formation
4. Fibroatheroma formation
5. Complicated lesion formation

Question 2

List the target levels for:

a) Cholesterol
b) Triglycerides
c) HDL (in men and women)
d) LDL

Answer 2

Cholesterol: <5 mmol/L (IDEAL: <3 mmol/L)

Triglycerides: <2.3 mmol/L

HDL: 1.0+ mmol/L
in MEN: 1.3 mmol/L
in WOMEN: 1.5 mmol/L

LDL: 1.3-1.8 mmol/L

Question 3

Briefly describe the exogenous cholesterol transport system. (4)

Answer 3

1. Cholesterol absorbed from gut, packaged into chylomicrons
   a. Absorbed via lacteal
2. Chylomicrons broken down via peripheral tissue expressing LPL
   a. Release cholesterol into tissue
   b. Forms chylomicron remnants and empty HDL
3. Empty HDL recycled as HDL by liver
4. Chylomicron remnants bind to remnant receptor on liver (via ApoE on the remnant surface)
   a. Remnants broken down into fatty acids and glycerol in liver

Question 4

Briefly describe the endogenous cholesterol transport system. (6)

Answer 4

1. Cholesterol produced in liver; packaged into VLDL
   a. Released into bloodstream
2. VLDL broken down by peripheral tissues expressing LPL
   a. Releases cholesterol and empty HDL
   b. Turns into IDL
3. IDL transported back into liver, where it is absorbed
4. Hepatic lipase breaks down IDL into LDLs
5. LDL released into bloodstream; absorbed by cells expressing LDL receptors
6. Excess LDL taken up by liver via LDL receptors
   a. Liver uses cholesterol to form bile salts

Question 5

What treatment is used to lower lipid levels? (5)

Answer 5

1. Lifestyle changes
2. Statins
3. Ezetimibe
4. PCSK9 inhibitors
5. Fibrates

Question 6

Describe lifestyle changes to lower lipid levels. (2)

Answer 6

Regular exercise

Good diet

Question 7

Give 4 examples of statins.

Answer 7

Simvastatin
Pravastatin
Atorvastatin
Rosuvastatin

Question 8

What is rhabdomyolysis (a rare side effect of statin use)?

Answer 8

Severe, generalised inflammation of muscle cells resulting in evidence of muscle breakdown (including myoglobinuria, myoglobinaemia) with or without complications (e.g. renal impairment)

Question 9

Describe the mechanism of action of ezetimibe. (1)

List 3 indications for ezetimibe.

Answer 9

MECHANISM OF ACTION:
1. Inhibits cholesterol absorption in the small intestine

INDICATIONS:
Adjunct to dietary measures
Adjunct to statin treatment
Primary treatment if intolerant to statins

Question 10

List 8 side effects of ezetimibe.

Answer 10

GI disturbance
Headache
Fatigue
Myalgia
Arthralgia (rare)
Allergy
Myopathy
Rhabdomyolysis

Question 11

Describe the mechanism of action of PCSK9 inhibitors. (2)

Answer 11

1. Inhibit PCSK9 proteins, which normally remove LDL receptors from the liver surface and degrade them
2. Therefore there are more LDL receptors on the liver
   a. Therefore more LDL is absorbed by the liver, decreasing circulating LDL levels

Question 12

Give 2 examples of PCSK9 inhibitors.

Answer 12

Alirocumab

Evolocumab

Question 13

Describe the mechanism of action of fibrates. (1)

List 5 indications for fibrate use.

Answer 13

MECHANISM OF ACTION:
1. Lower triglyceride levels

INDICATIONS:
Triglyceride levels 10+ mmol/L
Risk of pancreatitis
Potential alcohol excess
Diabetes/obesity
Renal disease

Question 14

List 5 non-modifiable cardiovascular risk factors.

Answer 14

Age
Male
Ethnicity (eg. South Asians)
Family history
Socioeconomic status

Question 15

List 5 modifiable cardiovascular risk factors.

Answer 15

Hypertension
Smoking
Hypercholesterolaemia
Diabetes
Obesity

Question 16

Give 2 examples of fibrates.

Answer 16

Gemfibrozil

Fenofibrate