Hyperlipidaemia

Question 1

What do you know about Familial hypercholesterolaemia? (4)

Answer 1

Autosomal dominant

Defective or absent LDL receptor

Homozygous - MI before age of 20 (chol level = 10-fold)

Heterozygous - MI in 30-40s, 70% before 60s (chol level = 2-3 fold)

Question 2

If a patient knows that Triglyceride level has been very high and there is history of pancreatitis, what condition do you suspect?

Answer 2

Familial Hyper-Triglyceri-daemia (autosomal dominant)

Associated with obesity, diabetes, HTN and hyperuricaemia

Question 3

What are the triggers of pancreatitis or eruptive xanthomas in patients with familial hypertricholesterolaemia?

Answer 3

Followings can precipitate rapid rise in triglyceride level and precipitate pancreatitis or eruptive xanthomas

1. Alcohol consumption
2. Hypothyroidism
3. Ingestion of oestrogen containing OCPs

Question 4

What are the clinical signs of familial hypercholesterolaemia? (4)

Answer 4

Tendon Xanthomas (the only specific sign)

Xanthalasma

Eruptive xanthomas (familial hypertriglyceridaemia - whee TG often ≥20 mmol/L)

Corneal arcus (but common over >50 yo, so only important when found in young)

Question 5

How would you manage this patient’s dyslipidaemia?

Answer 5

Goals

• Minimise morbidity and mortality associated with hypercholesterolaemia

Confirm diagnosis

• Fasting LDL, HDL, TG, cholesterol

Association/causative factors

• TFT (hypothyroidism), Fasting glucose / HBA1C (diabetes), Alcohol history

Non-pharmacological

• Education - importance of controlling lipids in minimising life-threatening complications
• Lifestyle changes: reduce ETOH, smoking, exercise (30min 5/wk), weight loss
• Diet: Mediterranean diet, Plant-sterol enriched dairy products (most effective way), reduce salt intake, increase Fish, Fruit, Veg, reduce saturated / trans fats

Pharmacological

• Statins (HBG-CoA reductase inhibitor)
• Fibrates
• Ezetimibe
• PCSK9 inhibitors (evolocumab, alirocumab)
• Bile acid binding resins (cholestyramine)

Regular follow-up

• Continue to support and encourage
• Screen complications: cardio/cerebro/peripheral/reno-vascular disease
• Physical examinations, BP, ECG, TTE, ABPI, renal dopplers, CTB

Question 6

When should statin be taken and why (so should check when patient takes their statin)?

Answer 6

At night as they are relatively short-acting and most cholesterol is manufactured at night.

Exception is Atorvastatin (can be taken any time)

Question 7

Which 2 are the most potent statins?

Answer 7

Atorvastatin

Rosuvastatin

Question 8

Side effects of statins? (4)

Answer 8

Myalgia

Myositis

Abnormal LFTs

GI symptoms

Question 9

Ezetimibe mechanism of action thus side effects? (2)

Answer 9

Inhibits intestinal absorption of cholesterol from the gut - hence interrupting it’s enterohepatic circulation.

Side Fx: diarrhoea, raised LFTs

Question 10

Fibrates (fenofibrate, gemfibrozil) side effects? (4)

Answer 10

GI disturbances

Pancreatitis

Gall-stones

Raised creatinine

Question 11

PCSK9 inhibitors MoA and side effects (4)?

Answer 11

PCSK9 Causes internalisation of LDL receptor + its degradation. Inhibiting PCSK9 leads to recycling of LDL receptor to cell surface → it continues to clear LDL from circulation

Injection site reactions

Nasopharyngitis

URTI

Neurocognitive effects

Question 12

Are there any other pharmacological strategy?

Answer 12

Some people use bile-sequestrants (e.g. cholestyramine / cholestipol)

Problem is that there is compensatory increase in hepatic cholesterol synthesis - so one could consider using Nicotinic acid (which blocks this).

Question 13

What are the side effects of Bile sequestrants? (5)

Answer 13

Constipation

Flatulence

Block absorption of other drugs

Question 14

Side effects of nicotinic acids? (5)

Answer 14

Flushing

Hyperglycaemia

Pruritis

Abnormal liver function

Aggravates PUD