Dyslipidaemia Flashcards
Physiological Importance of Lipids
Highest energy yielding metabolic fuel Fat soluble vitamins absorption Heat insulating and shock protection Cell membrane constituent Steroid biosynthesis Nerve conduction
Normal lipid and lipoprotein metabolism
Exogenous cycle
- diet to liver/peripheral tissues
- by chylomicrons and chylomicron remnants
Endogenous cycle
- liver to peripheral tissues
- by VLDL – IDL – LDL
Reverse cholesterol transport
- peripheral tissues/ CM/ VLDL/ IDK to liver
- by HDL
Low solubility of lipids = need carrier for transport in blood
- lipoproteins, hormone binding proteins
- apolipoproteins attached to lipoproteins acting as receptor to divert and regulate circulation of lipoproteins in body
Major apolipoproteins
ApoA-I: HDL –> activates LCAT, structural
Apo(a): Lp(a) –> structural (also arthrogenic)
ApoB-100: VLDL, IDL, LDL, Lp(a) –> ligand for binding to LDL receptor
ApoC-II: Chylomicrons –> cofactor for LPL (lipoprotein lipase for metabolism of TG)
ApoE: CMR, IDL, HDL –> ligand for binding to LDL receptor and other receptor
Classification of lipoproteins
Chemical content, density and charge
CM - TRIGLYCERIDES (86%)
VLDL - TG 55%, cholesterol 12%
LDL - CHOLESTEROL (42%)
HDL - cholesterol 13%, TG 3%
Why are lipids important?
RISK FACTOR FOR ATHEROSCLEROSIS! (especially LDL)
–> stroke, AMI, secondary HT (kidney), claudication
**Clinical approach to dyslipidaemia
- Test validity (any acute stress, concurrent drug use, paraproteins?, LITHIUM HEPARIN TUBE (GREEN))
- Pattern recognition
- hyper/hypo
- cholesterol or TG? which lipoprotein? (LDLC, Non HDLC) - CVS risk factors and risk calculation
- Look for secondary causes (Hx and Ix)
- If primary defect: Fam hypercholesterolaemia scoring systems, Fam cascade screening
- Consider acute Tx (risk of acute pancreatitis)
- Chronic Tx (underlying cause, lipid control, control CVS risk)
- Monitor response and complications
Hypercholesterolaemia DDx
First consider secondary causes:
- DM
- Hypothyroidism
- Nephrotic Syndrome
- Cholestasis
- Ig disorders
- Anorexia nervosa
Primary causes
- familial hypercholesterolaemia (FH) –> single gene defect of LDL receptor, ApoB-100 or PCSK9
- sitosterolaemia (rare)
Hypertriglyceridaemia DDx
Secondary:
- post-prandial (but not necessarily in everyone; even if normal after fasting still suggests higher risk)
- DM
- renal failure
- (hypothyroidism)
- alcoholism
- nephrotic syndrome
- oestrogen/ steroid excess
Primary:
- familial hypertriglyceridaemia –> deficiency of LPL or ApoC-II (can’t metabolise exogenous TGs leading to increased risk of pancreatitis)
Combined hypercholesterolaemia and hyperTG DDx
Familial dysbetalipoproteinaemia (broad beta band disease) –> diagnosis by electrophoresis and ApoE genotyping
Lab investigations of Dyslipidaemia
- Lipid profile
- total cholesterol, HDL, TG, LDL (direct/calculated - Friedewald equation)
- non-HDLC - Lipoprotein pattern
- generally not needed unless strange/spurious lipoproteins
- visual, overnight standing, electrophoresis, ultracentrifugation - Apolipoprotein measurements (apoB, apoA1 and Lp(a))
- Secondary causes
- Hx e.g. drug (OCP), alcohol, diet (other signs/ symptoms), and FHx of IHD
- TFT, RLFT, fasting glucose, HbA1c, urinary protein - Genetic tests if [4] excluded
- scoring system - Atherosclerosis risk assessment
- Side effects of drug treatment
Cut-off values
Fasting
- cholesterol <5
- TG <1.7
- HDL-C >1
- LDL-C <3.0
- Non-HDL-C <3.8
Treatment goals based on CVS risk
Very high risk e.g. CHD or CHD equivalent risk such as previous stoke, DM
- LDL-C <1.8; Non-HDL-C <2.6
High risk (>2 risk factors e.g. smoking, HT, FHx) - LDL <2.5; HDL <3.3
Caution in interpretation of LDL
LDL decreases in acute events e.g. AMI
–> take blood within 24hrs of acute onset or wait until 4-6 wks after patient recovered
Friedewald equation for LDL-C
- Total cholesterol - HDL- VLDL (or TG/2.2)
- ONLY VALID IF TG <4.5 mmol/L, no abnormal IDL present
- can use direct LDL measurement or non-HDL-C (cholesterol - HDl-C) if LDL-C invalid
Now acceptable to use non-fasting samples – proven to have no significant difference in lipid profiles (safer, more convenient, time-efficient, patient friendly)
Lipoprotein analysis - visual, electrophoresis
Visual
- hazy when TG >2.3 mmol/L
- Turbid sample = excessive CM or VLDL – CM usually creamy top layer with uniform clear bottom; VLDL denser so expect even distribution throughout sample with turbid bottom plasma
- Clear sample – may be excessive LDL
Ultracentrifugation (obsolete now)
- physical separation by density
Electrophoresis
- indicated when lipid profile not correlated with lipoprotein profile e.g. high cholesterol but LDL normal
- CM > LDL > VLDL > HDL > Free fatty acids
- no chylomicrons normally (fasting)
WHO-Fredrickson classification of lipid disorder (clinically not useful)
I: Chylomicron -- TG IIa: LDL -- Cholesterol IIb: LDL + VLDL -- mixed III: IDL -- mixed IV: VLDL -- TG V: CM and VLDL -- TG and some cholesterol
Need to Ix whether VLDL or CM are causing hyperTG (appearance and VLDL would also cause elevated cholesterol)
Cholesterol – RISK OF CHD
Chylomicrons – RISK OF PANCREATITIS
Secondary hyperlipidaemia (lipid profiles)
DM – cholesterol and TG
Nephrotic syndrome – cholesterol and TG
Hypothyroidism, biliary obstruction, acute porphyria – cholesterol
Pancreatitis, renal failure, alcoholism, OCP, glycogen storage disease – TG
Further investigations:
- DM (glucose, HbA1c)
- Nephrotic (oedema, RFT, LFT, urine protein)
- **Hypothyroid (TFT) - most common cause after high cholesterol diet (reduced LDL-R and lipoprotein lipase activity)
- Cholestasis (LFT)
