Lipids and lipoproteins

Question 1

Describe the structure of a lipoprotein

Answer 1

1. Lipid core consisting of cholesterol esters and triglycerides
2. Lipid membrane - monolayer consisting of free cholesterol and phospholipids
3. Apoproteins attached to surface

Question 2

What percentage of total plasma cholesterol is carried by LDL?

Answer 2

70%

Question 3

Pros of using the Friedewald formula

Answer 3

1. Well-established and extensive experience
2. Convenient and inexpensive

Question 4

Cons of Friedewald formula

Answer 4

1. Value estimated from 3 independent measures, each with their own errors
2. Not usable when Tg > 4.5 mmol/L (VLDL-C assumption does not hold up)
3. Not usable in familial combined hyperlipidaemia/familial chylomicronaemia/dysbetalipoproteinaemia)

Question 5

For patients with Tg > 4.5mmol/L, which is recommended - non-HDL-C or direct LDL-C?

Answer 5

Non-HDL-C

Question 6

What is the utility of non-HDL-C?

Answer 6

1. When Tg are high and LDL-C cannot be calculated
2. Secondary target when serum Tg > 2.3 mmol/L in pts with diabetes mellitus/metabolic syndrome

Question 7

Pros and cons of ApoB measurement

Answer 7

Pros: reflect particle number - the best lipid-based determinant of ASCVD risk, when LDL-C deplete particles present (diabetes, insulin resistance, obesity, metabolic syndrome, hypertriglyceridaemia) LDL-C can underestimate risk, relatively well standardised, automated and inexpensive
Cons: physicians unfamiliar with ApoB, guidelines still promote LDL-C, treatment is based on LDL-C lowering, ApoB still not widely offered

Question 8

Alternatives to Friedewald equation

Answer 8

Sampson equation
Martin/Hopkins equation

Question 9

Causes of increased Tg

Answer 9

Primary:
Exogenous hyperlipaemia (Familial chylomicronaemia syndrome) - Tg +++
Polygenic/combined hyperlipidaemia
Polygenic chylomicronaemia
Polygenic hypertriglyceridaemia
Dysbetalipoproteinaemia
Hyperalphalipoproteinaemia (with increased TC)
Secondary:
Diabetes mellitus, insulin resistance, obesity
NAFLD (usually normal LDL-C and low HDL-C)
Glucocorticoids
Ethinyl oestradiol
Anabolic steroids
Tamoxifen
Diuretics (chlorothiazide)
Alcohol (not LDL-C)

Question 10

Causes of increased Tg

Answer 10

Primary:
Familial chylomicronaemia
Polygenic chylomicronaemia
Combined dyslipidaemia*
Dysbetalipoproteinaemia (APOE)*
Hyperalphalipoproteinaemia

Secondary:
Diabetes
Obesity
Alcohol
Cholestasis
Hypothyroidism
Nephrotic syndrome
Glucocorticoids, androgens, oestrogens
Fatty meal

Question 11

Which lipoproteins is ApoB-100 associated with?

Answer 11

VLDL, IDL, LDL, Lp(a)

Question 12

Which lipoproteins is ApoB-48 associated with?

Answer 12

Chylomicrons

Question 13

Which lipoproteins is ApoA-I associated with?

Answer 13

Chylomicrons, HDL

Question 14

Which lipoproteins is ApoA-II associated with?

Answer 14

HDL, Chylomicrons

Question 15

Which lipoproteins is ApoE associated with?

Answer 15

CM, CM remnants, VLDL, IDL, HDL

Question 16

Major lipid in Chylomicron

Answer 16

Exogenous triglycerides

Question 17

Major lipid in VLDL

Answer 17

Endogenous triglycerides

Question 18

Major lipid in IDL

Answer 18

Tg and CE 50:50

Question 19

Major lipid in LDL

Answer 19

CE

Question 20

Major lipid in HDL

Answer 20

Phospholipids

Question 21

What is the role of microsomal transfer protein?

Answer 21

To add lipids to ApoB

Question 22

Consequences of mutations in microsomal transfer protein

Answer 22

Abetalipoproteinaemia AKA hereditary acanthocytosis

Question 23

Physiological functions of apolipoproteins

Answer 23

1. Structural
2. Receptor ligands
3. Cofactors for enzymes
   4.

Question 24

Modifications of LDL

Answer 24

Oxidation
Aldehyde substitution of lysine (post-ischaemia on ApoB)
Glycation
Carbamylation

Question 25

Friedewald equation assumptions

Answer 25

1. Fasting
2. VLDL composition is normal
3. No IDL
4. No Lp(a)
5. Tg < 4.5 mmol/L