2. Dyslipidaemias Flashcards
What PMHx and FHx do we need to check when assessing dyslipidaemias?
Symptoms
- dyspnoea, angina, claudication
- thirst or polyuria
- muscle or joint pains
Concomitant diseases Smoking Alcohol Exercise Diet Age at menopause FMH - CVD, age of first life event, vital status Meds - previous lipid therapy, steroids, cyclosporine
What would we do in an examination to assess for dyslipidaemias?
- Weight / Height^2 —> BMI; waist circumference
- dipstick urinalysis - proteinuria
- inspect for stigmata of hyperlipidaemia - eyes; Achilles and digital extensor tendons; knees and elbows; palms and flexures
- CVS exam - heart sounds, pulses, bruits
- BP
What are the basic serum lipid measurements we would assess?
Total cholesterol
- includes both atherogenic (LDL, IDL and VLDL), and anti-atherogenic fractions (HDL)
HDL cholesterol
- anti-atherogenic fraction, essential for risk assessment
TGs
- not considered directly atherogenic, but risk modifier
- after fasting for 14 hrs, there should be no CM left in blood, so if TGs are high at that point, you know it’s VLDL
How do we calculate lipid variables?
LDL
- most important class of atherogenic lipoproteins
- Friedewald equation: LDL = TC - (HDL + TG/2.2)
- important for diagnosis of FH
Non-HDL cholesterol
- total atherogenic lipoproteins, can be used when TG are elevated or pt is not fasting - simpler to calculate than LDL
- Non-HDL = TC - HDL
- preferred for assessment of response to treatment
- both can be used
- LDL calculation assumes constant cholesterol/TG ratio in VLDL (requires fasting to ensure absence of postprandial lipoproteins eg CM)
Why do we measure apolipoproteins?
ApoA1
- structural and functional apolipoprotein of HDL particles
- each HDL may contain MULTIPLE COPIES
- ApoA1 concs correlate with HDL
ApoB
- Each of the atherogenic lipoproteins (LDL, IDL, VLDL) have ONE COPY of ApoB100
- CMs have ApoB48
Lipoprotein a
- highly atherogenic modified form of LDL
- has polymorphic plasminogen-like apolipoprotein(a) covalent linked to ApoB100
- makes it sticky, and so can get into artery wall and is hard to get out
What did the INTERHEART study find?
They found that the two most important CHD risk factors were smoking and dyslipidaemia (ApoB/ApoA1 ratio)
- the higher the ratio, the higher the risk
What is a secondary dyslipidaemia?
A dyslipidaemia that occurs secondary to a different illness
- DM
- Alcohol excess
- Obesity
- Gout
- Pregnancy
Or drug treatment
- anticonvulsants
- beta blockers
- corticosteroids
- need to rule out any of these before making a primary dyslipidaemia diagnosis
What are the key investigations that need to be done to rule out secondary dyslipidaemias?
Renal profile - exclude renal failure
Liver profile - exclude cholestasis, M protein
Thyroid profile - exclude hypothyroidism
Glucose or HbA1C - exclude diabetes
Dipstick urinalysis - exclude nephrotic syndrome
What are the main types of primary hyperlipidaemia?
Familial hypercholesterolaemia
Familial combined Hyperlipidaemia (FCH)
Remnant (type III) hyperlipidaemia
Familial hypertriglyceridaemia
What is the mechanism for FH?
- decreased receptor mediated clearance of LDL
- due to mutation in LDLR, ApoB or PCSK9
What lipid profile is seen in FH?
High LDL
TC 9-12mM
Low or normal fasting TG
How is FH inherited?
AD
What are the physical signs of FH?
Tendon xanthomas
Corneal arcus
Plantar digital and nasal cleft cutaneous xanthomas
Aortic stenosis
What are the diagnostic criteria for FH?
- TC > 7.5mM, or LDL > 4.9mM
- tendon xanthomas in patient, 1st or 2nd degree relative
- DNA based evidence of LDLR mutation, familial defective ApoB100 or PCSK9 mutation
- FHx of premature MI
- FHx of raised TC
FH is definite if 1 + (2 or 3) are present
FH is possible if 1 + (4 or 5) are present
What is the mechanism of FCH?
- Overproduction of VLDL and ApoB
- genetic cause unknown - probably multigenic
