Lipids and lipoproteins Flashcards
Describe the structure of a lipoprotein
- Lipid core consisting of cholesterol esters and triglycerides
- Lipid membrane - monolayer consisting of free cholesterol and phospholipids
- Apoproteins attached to surface
What percentage of total plasma cholesterol is carried by LDL?
70%
Pros of using the Friedewald formula
- Well-established and extensive experience
- Convenient and inexpensive
Cons of Friedewald formula
- Value estimated from 3 independent measures, each with their own errors
- Not usable when Tg > 4.5 mmol/L (VLDL-C assumption does not hold up)
- Not usable in familial combined hyperlipidaemia/familial chylomicronaemia/dysbetalipoproteinaemia)
For patients with Tg > 4.5mmol/L, which is recommended - non-HDL-C or direct LDL-C?
Non-HDL-C
What is the utility of non-HDL-C?
- When Tg are high and LDL-C cannot be calculated
- Secondary target when serum Tg > 2.3 mmol/L in pts with diabetes mellitus/metabolic syndrome
Pros and cons of ApoB measurement
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
Alternatives to Friedewald equation
Sampson equation
Martin/Hopkins equation
Causes of increased Tg
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)
Causes of increased Tg
Primary:
Familial chylomicronaemia
Polygenic chylomicronaemia
Combined dyslipidaemia*
Dysbetalipoproteinaemia (APOE)*
Hyperalphalipoproteinaemia
Secondary:
Diabetes
Obesity
Alcohol
Cholestasis
Hypothyroidism
Nephrotic syndrome
Glucocorticoids, androgens, oestrogens
Fatty meal
Which lipoproteins is ApoB-100 associated with?
VLDL, IDL, LDL, Lp(a)
Which lipoproteins is ApoB-48 associated with?
Chylomicrons
Which lipoproteins is ApoA-I associated with?
Chylomicrons, HDL
Which lipoproteins is ApoA-II associated with?
HDL, Chylomicrons
Which lipoproteins is ApoE associated with?
CM, CM remnants, VLDL, IDL, HDL
Major lipid in Chylomicron
Exogenous triglycerides
Major lipid in VLDL
Endogenous triglycerides
Major lipid in IDL
Tg and CE 50:50
Major lipid in LDL
CE
Major lipid in HDL
Phospholipids
What is the role of microsomal transfer protein?
To add lipids to ApoB
Consequences of mutations in microsomal transfer protein
Abetalipoproteinaemia AKA hereditary acanthocytosis
Physiological functions of apolipoproteins
- Structural
- Receptor ligands
- Cofactors for enzymes
4.
Modifications of LDL
Oxidation
Aldehyde substitution of lysine (post-ischaemia on ApoB)
Glycation
Carbamylation
Friedewald equation assumptions
- Fasting
- VLDL composition is normal
- No IDL
- No Lp(a)
- Tg < 4.5 mmol/L
