Hyperlipidaemia (E&M)

Question 1

Define hyperlipidaemia.

Answer 1

Elevated blood lipid levels (total cholesterol, LDL, triglycerides)

Question 2

What are the different classes of lipids? (4)

Answer 2

• chylomicrons
• VLDL (triglyceride)
• LDL (cholesterol)
• HDL (phospholipid)

Question 3

What are some causes of hyperlipidaemia? (7)

Answer 3

• obesity
• DM
• physical inactivity
• hypothyroidism
• nephrotic syndrome
• alcohol
• cholestatic liver disease

Question 4

How can hypertriglyceridaemia be classified?

Answer 4

• primary or secondary
• increased VLDL, reduced VLDL clearance or both

Question 5

What is primary hypertriglyceridaemia?

Answer 5

• familial hypertriglyceridaemia (types IV and V)
• familial combined dyslipidaemia (types IIb and IV)
• polygenic hypocholesterolaemia (type IIb) and broad beta disease (type III)

Question 6

What medications can cause hypertriglyceridaemia?

Answer 6

• glucocorticoids
• oestrogens
• 13-cis-retinoic acid (Accutane)
• some antihypertensives (hydrochlorthiazide and non-selective beta-blockers), antiretroviral therapy, interferons

Question 7

What is hypercholesterolaemia?

Answer 7

• as a result of abnormal lipoprotein metabolism
• reduction of LDL receptor expression or activity
• diminishes hepatic LDL clearance from plasma
• common primary hyperlipidaemia (only LDL high) - accounts for 70%

Question 8

What is familial hypercholesterolaemia (FH)?

Answer 8

• autosomal dominant inherited disorder
• caused by a mutation in the gene coding the LDL receptor
• causes early-onset hypercholesterolaemia and hyperlipidaemia –> CVD in young patients

Question 9

What does hyperlipidaemia increase risk of?

Answer 9

Elevated LDL and reduced HDL –> promote atherosclerosis –> increased risk of cardiovascular events

Question 10

What is mixed hyperlipidaemia?

Answer 10

Both LDL and triglycerides high - due to T1DM, metabolic syndrome, alcohol abuse, chronic renal failure

Question 11

What are the clinical features of hyperlipidaemia? (5)

Answer 11

• xanthomata - nodular lipid deposits in the skin and tendons
• xanthoma - tendinous especially Achilles tendon, elbow and knee tendons, and over MCPJs
• xanthelasma - yellow, flat plaques on upper eyelids (xanthoma of eyelid)
• corneal arcus - grey/white crescentic-shaped opacity at the periphery of the cornea (xanthoma of the cornea)
• lipaemia retinalis - retina is pale and retinal vessels are white

Question 12

What specific clinical features may be found in familial hypercholesterolaemia?

Answer 12

May also have planar xanthomas (orange streaks in palmar creases) and tuberous xanthomas (plaques on elbows and knees), alongside other features of hyperlipidaemia e.g. xanthelasma, corneal arcus

Question 13

What are some risk factors for hyperlipidaemia? (9)

Answer 13

• excess body weight (BMI>25)
• insulin resistance and T2DM
• physical inactivity
• hypothyroidism
• nephrotic syndrome
• smoking and alcohol
• cholestatic liver disease
• use of certain medications
• family Hx of hyperlipidaemia

Question 14

What is the first-line main investigation that is done for hyperlipidaemia?

Answer 14

Serum lipid profile - total cholesterol, LDL, HDL, triglycerides

Question 15

What does a serum lipid profile look like in hyperlipidaemia?

Answer 15

• total cholesterol >5mmol/L (>200mg/dL)
• LDL >2.6mmol/L (>100mg/dL)
• HDL <1mmol/L (<50mg/dL)
• triglycerides >1.7mmol/L (>150mg/dL)

Question 16

What other investigations can we do for hyperlipidaemia? (5)

Answer 16

• lipoproteins - values >50mg/dL or >125nmol/L are high
• TSH - may be high in primary hypothyroidism
• HbA1c/fasting glucose
• LFTs
• urinalysis

Question 17

What score do we calculate in hyperlipidaemia and why?

Answer 17

QRISK2 - screens for risk of CVD (>10% is important)

Question 18

What are some differential diagnoses for hyperlipidaemia? (7)

Answer 18

• diabetes
• hypothyroidism
• nephrotic syndrome
• obstructive liver disease
• chronic renal insufficiency
• medications
• HIV

Question 19

What diagnostic criteria is used for clinical diagnosis of familial hypercholesterolaemia?

Answer 19

Simon Broome criteria:

• in adults TC>7.5mmol/L and LDL-C>4.9mmol/L OR children TC>6.7mmol/L and LDL-C>4.0mmol/L PLUS
• for definite FH: tendon xanthoma in patients 1st/2nd-degree relatives or DNA-based evidence of hyperlipidaemia
• for possible FH: Fx of MI <50y in 2nd-degree relative, <60y in 1st-degree relative, or Fx raised cholesterol levels

Question 20

What lifestyle modifications can we prescribe for hyperlipidaemia? (5)

Answer 20

• diet - <7% calories from saturated fat, high fibre, fresh fruit and veg, Omega-3 FA
• physical activity
• weight management (aim for BMI 20-25)
• alcohol intake reduction
• stop smoking

Question 21

What is the management for hyperlipidaemia if QRISK<10%?

Answer 21

Lifestyle modifications (as above)

Question 22

What is the first-line management for hyperlipidaemia if QRISK>10% (primary prevention)?

Answer 22

Atorvastatin 20mg (alternative: Simvastatin) - decreases cholesterol synthesis by inhibiting HMG-CoA reductase

Question 23

What secondary prevention is there for hyperlipidaemia with known IHD/cerebrovascular disease/PAD?

Answer 23

Atorvastatin 80mg

Question 24

Who are statins contraindicated in?

Answer 24

Pregnant women

Question 25

What other medications do statins have an important interaction with?

Answer 25

Erythromycin/clarithromycin (macrolides) - can cause myopathy and increase likelihood of rhabdomyolysis

Question 26

What time of day should statins be taken in hyperlipidaemia?

Answer 26

Last thing at night to improve efficacy

Question 27

When should statin treatment be discontinued?

Answer 27

If serum transaminase concentrations rise to and persist at 3x the upper limit of reference range

Question 28

What is the second-line treatment for hyperlipidaemia if intolerance to statins?

Answer 28

Ezetimibe - cholesterol absorption inhibitor

Question 29

How can we treat xanthelasma if it is affecting patient's activities of daily living?

Answer 29

Laser therapy or surgical excision

Question 30

How do we manage hyperlipidaemia with triglycerides>5.7?

Answer 30

Fibric acid derivatives or fish oil

Question 31

How do we manage hyperlipidaemia with LDL>4.92?

Answer 31

High intensity statin (40-80mg atorvastatin)

Question 32

How do we manage hyperlipidaemia with CVD/diabetes?

Answer 32

High intensity statin (20mg atorvastatin)

Question 33

How do we manage hyperlipidaemia if >75y or other presentation?

Answer 33

Moderate intensity statin

Question 34

What medications are used in hyperlipidaemia?

Answer 34

- statins - high intensity: primary prevention (atorvastatin 20mg), secondary prevention (atorvastatin 80mg) - low intensity (simvastatin 10mg and 20mg) - fibrates - bezafibrate, cholesterol absorption inhibitors (ezetimibe, PCSK9 inhibitors)

Question 35

What are the treatment priorities regarding statins for hyperlipidaemia?

Answer 35

- using statins in primary prevention may cause side effects and be expensive - 1st priority: all those with known CVD - 2nd: all those with DM - 3rd: those with 10y risk of CVD>20% - aim for target plasma cholesterol

Question 36

What are some complications of hyperlipidaemia? (5)

Answer 36

- CAD - stroke - PVD - high triglycerides --> pancreatitis - statin toxicity