W2 - Lipoprotein metabolism, CVD, obesity

Question 1

Name 3 components of an atherosclerotic mass in a vessel

Answer 1

1. necrotic core with cholesterol crystals/deposits
2. Foam cells
3. Fibrous cap

Question 2

In what 4 forms can fats move within the plasma?

Answer 2

chylomicrons
VLDL
LDL
HDL

Question 3

In fasting plasma, what % of cholesterol is in each form?

Answer 3

chylomicrons (<5%)
VLDL (13%)
LDL (70%)
HDL (17%)

Question 4

In fasting plasma, what % of TG is in each form?

Answer 4

chylomicrons (<5%)
VLDL (55%)
LDL (29%)
HDL (11%)

Question 5

What are the 4 diseases that fall under dyslipidaemia?

Answer 5

1. Hypercholesterolaemia
2. Hypertriglyceridaemia
3. Mixed hyperlipidaemia
4. Hypolipidaemia

Question 6

What is the inheritance mode of familial hypercholesterolaemia? What gene is involved?

Answer 6

Dominant
mutations of LDL receptor, apoB or PCSK9

*rarely autosomal recessive inheritance

Question 7

What is the incidence of familial hypercholesterolaemia?

Answer 7

1/10^6

Question 8

Name a few clinical features (4) found in familial hypercholesterolaemia?

Answer 8

corneal arcus
Xanthelasmas
tendon xanthoma
atheroma of aortic root

Question 9

Describe MOA of mutations in PCSK9

Answer 9

dominant GAIN of function mutation of PCSK9 lead to increased PCSK9 activity, which functions to bind to LDL R and promote its degradation –> hence FH

Question 10

Name the 3 types of primary hypertriglyceridaemia and the aetiology

Answer 10

1. Familial type I - lipoprotein lipase or apoC II deficiency
2. Familial type IV - increased synthesis of TG (? cause)
3. Familial type V - sometimes due to apoA V deficiency

Question 11

Name the 3 types of primary mixed hyperlipidaemia

Answer 11

1. Familial combined hyperlipidaemia (? cause)
2. Familial hepatic lipase deficiency
3. Familial dysβlipoproteinaemia (type III)

Question 12

Name the 4 types of hypolipidaemia

Answer 12

1. Aβ-lipoproteinaemia: MTP deficiency (recessive)
2. Hypoβ-lipoproteinaemia: truncated apoB (dominant)
3. Hypoα-lipoproteinaemia: sometimes due to apoA-I mutations
4. Tangier disease: HDL deficiency caused by ABC AI mutations

Question 13

What is the relationship between incidence of coronary heart disease and serum cholesterol levels?

Answer 13

Positive - increase together

Question 14

What is the relationship between deaths from CHD and LDL cholesterol?

Answer 14

Positive - increase together

Question 15

What is the relationship between deaths from CHD and HDL cholesterol?

Answer 15

Negative - one increases, other decreases

Question 16

What is the relationship between CHD incidence and total cholesterol/HDL ratio?

Answer 16

Positive (exponential) - increase together

Question 17

Describe how macrophages are implicated in lipid-rich plaques?

Answer 17

Plasma LDL, once crossing the endothelial, becomes oxidised LDL - this signals to monocytes and causes chemoattractant migration of monocytes into the tissue, which becomes activated macrophages, and as macrophages uptake fatty fragments, they become foam cells.

Question 18

What is the effect of atorvastatin on LDL, HDL, and TG

Answer 18

LDL 51% reduction
HDL 5% increase
TG 32% reduction

Question 19

What is the effect of nicotinic acid on LDL, HDL, and TG

Answer 19

LDL 9% reduction
HDL 43% increase
TG 34% reduction

Question 20

What is the effect of Gemfibrozil on LDL, HDL, and TG

Answer 20

LDL 18% reduction
HDL 12% increase
TG 40% reduction

Question 21

What drug class does Gemfibrozil belong to? MOA?

Answer 21

fibrate - the MOA of gemfibrozil is not entirely understood. It increases VLDL clearance by stimulating vascular endothelial cell lipoprotein lipase activity.

Question 22

What drug class does nicotinic acid belong to? MOA?

Answer 22

antilipemic agents - main use is for pellagra (vit B3/niacin deficiency) but can be used as lipid-regulating medicine

Question 23

Name 3 novel forms of LDL-lowering therapy

Answer 23

Microsomal Triglyceride Transfer Protein (MTP) inhibitor (lomitapide)

Anti-PCSK9 monoclonal antibody (REGN727)

Anti-sense apoB oligonucleotide (mipomersen)

Question 24

_________ should be measured as a cardiovascular risk factor for those with intermediate or high CVD/CHD risk

Answer 24

lipoprotein A

Question 25

Name 2 novel HLD-based therapies

Answer 25

1. Apolipoprotein A-I or A-1 mimetic infusion therapy
2. Cholesterol ester transfer protein (CETP) inhibitors

Question 26

What is the treatment of obesity?

Answer 26

• Hypocaloric diet and exercise
• Iatrogenic malabsorption: Orlistat
  120 – 360 mg daily
• Bariatric surgery if BMI > 40 (Kg/m2) such as gastric banding, Roux- en- Y gastric bypass, biliopancreatic diversion

Question 27

Name 6 benefits to bariatric surgery

Answer 27

1. Success =>50% in excess weight (actual - ideal)
2. Diabetes reduction
3. Serum TG reduction
4. Serum HDL increase
5. Fatty liver reduction
6. Hypertension reduction

**risk of above are reduced

Question 28

Which of the following causes the most reduction in HbA1c in obese diabetics?

• gastric bypass
• biliopancreatic diversion
• medical therapy

Answer 28

biliopancreatic diversion > gastric bypass > medical therapy