Dyslipidaemia

Question 1

Secondary dyslipidaemia

Answer 1

Diet 
Sedentary lifestyle
Diabetes
Hypothyroidism
Obstructive liver disease
Meds: thiazide diuretics, progestins, anabolic steroids

Question 2

Primary dyslipidaemia

Answer 2

Familial hypercholesterolemia - autosomal dominant

• raised LDL
• premature atherosclerosis
• tendon xanthomatas

95% of FH carry a functional mutation of 1 of 3 genes

• LDL receptor (93%)
• apolipoprotein B which impairs binding of LDL to LDL receptor (5%)
• gain of fcn mutation in proprotein convertase subtilisin kexin 9 gene-> decreased LDL metabolism (2%)

Question 3

Deciding on tx for primary prevention

Answer 3

Relative risk reduction of 20-30% but small absolute risk reduction in someone with nil known CVD

Statin is 1st line: increase in mortality with non statin therapy so if intolerant of statin cease it, and lifestyle modification

No need to target a LDL level

10 yr Cardiovascular risk can be calculated with framingham risk score

Question 4

Tx for secondary prevention in stable CVD

Answer 4

Atorvastatin 80 irrespective of baseline LDL

Maximise statin therapy if do not achieve 50% reduction in LDL or below 2.6

If still bad on max statin therapy, add 2nd LDL lowering agent

Dont add 2nd agent if LDL near goal or below 1.8 but

Question 5

Statin

Answer 5

Mechanism of action ( endogenous pathway)

Competitive HMG CoA reductase inhibitor-> block pathway for synthesising cholesterol in liver
Reduction of intrahepatic cholesterol ->incr in LDL receptor turnover and hence increases LDL uptake
Reduce VLDL production via hepatic apo B secretion
Modest HDL raising properties (rosuvastatin largest effect)

Rosuvastatin, atorvastatin, simvastatin most potent at lowering LDL

Severe renal impairment: atorva and fluvastatin ( no need to dose adjust)

Chronic liver disease: ETOh abstinence and low dose pravastatin

Pravastatin and fluvastatin less likely to cause muscle toxicity

Baseline CK, TSH ( hypothyroidism may predispose to statin induced myopathy) and aminotransferase prior to starting statin useful

Question 6

Non lipid lowering effects of statin

Answer 6

• improve endothelial function
• modu,ate inflammatory response
• maintain plaque stability
• prevent thrombus formation

Question 7

Fibrates

Answer 7

Lower TGs and raise HDL

Activate peroxisome proliferator-activated receptors (PPAR)
Incr risk of non cardiac death

Lower TG by

Reduced hepatic secretion of VLDL
Help clear TG enriched lipoproteins by stimulating lipoprotein lipase activity (downregulate apolipoprotein C-III gene expression)

Incr HDL by

Direct stimulant of synthesis of HDL apolipoproteins AI and AII
Reduced chol transfer from HDl to VLDL while incr transfer of apoA
Less inhibition by VLDL on hepatic apoA synthesis

Question 8

Nicotinic acid

Answer 8

Not to be used in combination with statin

Inhibits hepatic VLDL and consequently its metabolite LDL
Incr HDL by reducing transfer of chol from HDL to VLDL and by delaying HDL clearance

Only for ppl with extreme high CV risk and unable to take other lipid lowering therapy

Common SEs: fushing, itchy, paresthesiae, nausea

Pre treatment with aspirin or ibuprofen can improve tolerability

Question 9

Ezetimibe

Answer 9

Chol absorption inhibitor at GI brush border w/o affecting TG and fat sol vitamin absorption

In combination with statin post ACS, provides extra small reduction in CV events

Question 10

Bile acid sequestrants

Answer 10

Mild to mod raised LDL

Effective in combination with statin or nicotinic acid in pts with markedly high LDL

Limited evidence for improved clinical outcomes

Common SE: bloating, cramping, nausea, can impair absorption of other drugs