T3 - Hyperlipidaemias

Question 1

when was the framingham heart study established and what was the purpose?

Answer 1

established in 1948 with the purpose to identify risk factors that contribute to CVD in those without CVD history

Question 2

what are the six major risk factors for CVD established from the FHS?

Answer 2

hypertension, smoking, obesity, high blood cholesterol, diabetes and low physical activity

Question 3

what risk factors does QRISK3 take into account?

Answer 3

age, sex, cholesterol:HDL ratio, BP, diabetes smoking

Question 4

what QRISK score means a patient should go on primary prevention of lipid lowering therapy?

Answer 4

> 10

Question 5

what is primary prevention of lipid lowering therapy?

Answer 5

statins

Question 6

in what situation may the QRISK score not be suitable for assessing risk?

Answer 6

in those with familial hypercholesteroleaemia or other inherited lipid metabolism disorders

Question 7

does a full lipid profile require a fasting blood sample?

Answer 7

no

Question 8

what three factors may lead to consideration of familial HCE?

Answer 8

total cholesterol >7.5mmol/L, history of HCE or premature CHD

Question 9

what is the dose and statin of choice for primary prevention?

Answer 9

20mg of atorvastatin

Question 10

what is the drug of choice and dose for secondary prevention (ie with previous history of CVD)

Answer 10

80mg atorvastatin

Question 11

what condition may be caused by lipid disorders and what is this associated with

Answer 11

pancreatitis associated with high serum triglycerides

Question 12

what ligand does LDL R recognise and where is this found?

Answer 12

ApoB-100 in the plasma membrane of LDL

Question 13

where are most LDL Rs present?

Answer 13

on hepatocytes in the liver

Question 14

what drug is used in patients that do not tolerate statins well?

Answer 14

ezetimibe

Question 15

what is the mechanism of action of ezetimibe and what does it cause?

Answer 15

• potent selective inhibitor of cholesterol absorption in the SI
• decreases cholesterol and Tis

Question 16

what is the mechanism of action of bile acid sequestrates and what does this cause?

Answer 16

bind bile acids in the intestine and stop recycling by interrupting enterohepatic circulation

• this causes increased conversion of cholesterol to bile acids in the liver
• also increases LDL R expression to remove cholesterols from the blood

Question 17

what enzyme do fibrate drugs activate and what does this cause?

Answer 17

lipoprotein lipase

• causes increased peripheral lipolysis, decreased hepatic TG production and increased reverse cholesterol transport
• decreases TG and increases HDL

Question 18

what does omega 3 inhibit and what does it promote?

Answer 18

inhibits lipogenesis and promotes beta oxidation of fatty acids

Question 19

what is the result of PCSK9 inhibitors and in what circumstance is it given?

Answer 19

increased LDL R on hepatocyte surface therefore increased LDL absorption
- only given to very high risk patients

Question 20

what are the three main patterns of lipoprotein abnormalities?

Answer 20

1) HCE
2) mixed hyperlipidaemia (dyslipidaemia)
3) hypertriglycerideamiea

Question 21

how is HCE characterised?

Answer 21

raised total and LDL cholesterol

- familial

Question 22

which patients is mixed HLE commonly seen in and what influences it?

Answer 22

patients with glucose intolerance and diabetes

- often influenced by lifestyle

Question 23

what may hypertriglycerideaemia cause?

Answer 23

pancreatitis

Question 24

what is the inheritance pattern of familial HCE and what is the incidence?

Answer 24

autosomal dominant and 1 in 200-250

Question 25

where are most mutations found in familial HCE and where are they found in 3% of all cases?

Answer 25

• most common mutations in LDL R

- 3% mutations in ApoB or GOF in PCSK9

Question 26

why may females develop CVD later in life?

Answer 26

they are protected by oestrogen

Question 27

what is the clinical presentation of familal HCE? (5 things)

Answer 27

tendon xanthoma (cholesterol accumulation in tendons), corneal arcus, skin bump, intimal thickening, diffuse arterial narrowing and low flow velocity

Question 28

how is familial HCE treated?

Answer 28

• low sat fat diet and exercise
• statins for all patients at any age
• may add cholesterol inhibitor eg ezetimibe
• anti PCSK9
• LDL aphesis - surgical removal of LDL
• self help and DNA testing