primary & secondary dyslipidaemias

Question 1

what does the Framingham heart study show the major cardiovascular risk factors as?

Answer 1

• high blood pressure
• high blood cholesterol
• smoking
• obesity
• diabetes
• physical inactivity

Question 2

what 3 things dos the cholesterol treatment trialists (CTT) collaboration show?

Answer 2

1) reduction of LDL cholesterol using statin therapy substantially reduces the risk of major vascular events (major coronary events, strokes, or the need for coronary revascularization) and vascular mortality
2) further reductions in LDL cholesterol with more intensive statin therapy produce further reductions in the incidence of major vascular events
3) is effective in a wide range of people including those with diabetes, male or female

Question 3

what are the modifiable risk factors for CVD?

Answer 3

• smoking
• obesity
• sedentary lifestyle
• high cholesterol or abnormal blood lipids
• hypertension
• excess alcohol intake

Question 4

what are the unmodifiable risk factors for CVD?

Answer 4

• age: >50 years
• gender: <64 men are much more likely to die than women
• genetic factors/family history
• pre-existing CVD

Question 5

what QRISK3 score indicates that primary prevention with lipid-lowering therapy should be considered?

Answer 5

score over 10

Question 6

what does the NICE lipid modification guideline say you need to measure before starting lipid modification therapy?

Answer 6

• total cholesterol (TC)
• high density lipoprotein cholesterol (HDL)
• non-HDL cholesterol
• triglyceride (TG)

Question 7

what causes does the NICE lipid modification guideline say you need to exclude before referring for specialist review?

Answer 7

• excess alcohol
• uncontrolled diabetes
• hypothyroidism
• liver disease
• nephrotic syndrome

Question 8

what mg of atorvastatin do you put a patient on if in primary prevention with no history of CVD?

Answer 8

20mg

Question 9

what mg of atorvastatin do you put a patient on if in secondary prevention with history of CVD?

Answer 9

80mg

Question 10

why do you treat asymptomatic lipid disorders?

Answer 10

• to reduce the atherosclerotic process and the incidence of clinical vascular disease
• to prevent pancreatitis which is associated with grossly increased serum triglyceride

Question 11

how do low density lipoprotein receptors (LDLR) work?

Answer 11

• LDLR is a cell surface receptor that recognises ApoB-100 which is embedded in the phospholipid outer layer of LDL particles
• present on most cells but the majority on the liver
• LDLR on hepatocytes binds to LDL particles and remove them from the circulation
• the LDLR then return to the cell surface to repeat this process

Question 12

what is ezetimibe?

Answer 12

a potent and selective inhibitor of absorption of cholesterol in the small bowel

Question 13

how does ezetimibe work?

Answer 13

the drug and its active glucuronide metabolite impair the intestinal reabsorption of both dietary and hepatically excreted biliary cholesterol through inhibition of a membrane transporter

Question 14

how do PCSK9 inhibitors work?

Answer 14

• functions as a binding protein
• it is expressed primarily in hepatocytes and after secretion binds to the LDLR and promotes their degradation
• by blocking PCSK9 these drugs result in increased availability of LDLR to remove LDLC from the circulation

Question 15

how are PCSK9 inhibitors given?

Answer 15

• monoclonal antibodies to PCSK9

- administered bimonthly as subcutaneous injections

Question 16

what are the 3 main profiles of lipid profiles?

Answer 16

1) hypercholesterolaemia
2) mixed hyperlipidaemia
3) hypertriglyceridaemia

Question 17

when is the hypercholesterolaemia profile seen?

Answer 17

in familial hypercholesterolaemia where total cholesterol levels may range between 7 and 20mml/L in heterozygotes but are even higher in the rare homozygotes

Question 18

when is the mixed hyperlipidaemia seen?

Answer 18

patients with glucose intolerance and diabetes and arises from the increased production and reduced breakdown of triglyceride rich lipoproteins

Question 19

when is the hypertriglyceridaemia seen?

Answer 19

less common, may be familial and tending to cause harm through acute pancreatitis

Question 20

what is apo (a)?

Answer 20

• type of lipoprotein (a)
• a glycoprotein, similar to plasminogen 300-800kDa
• physiological function in clear
• pathological function: atherosclerosis and thrombosis formation

Question 21

what is the measurement criteria for lipoprotein (a)?

Answer 21

• intermediate or high risk of CVD A
• subjects with premature CVD
• FH cases
• FhX premature CVD or raised Lp(a)
• recurrent CVD despite on statin treatment

Question 22

what are the treatments for lipoprotein (a)?

Answer 22

• lifestyle changes controlled trials show marginal effects so far or lacking evidence
• approved and investigational drive are present that lower Lp(a)
• 3 effective therapists on continued trial: lipid apheresis, PSCK9i, antisense therapy

Question 23

what is the clinical presentation of familial hypercholesterolemia (FH)?

Answer 23

• tendon xanthoma
• corneal arcus
• lipid deposits

Question 24

what is the treatment for familial hypercholesterolemia (FH)?

Answer 24

• low saturated fat diet and exercise
• statins
• possible addition of cholesterol absorption inhibitor
• rarely resins, surgery,y LDL pahersesis
• anti PCSK9
• involve patient self help group, offer DNA testing and get family tested

Question 25

what is familial hypercholesterolemia (FH)?

Answer 25

a common genetic disorder characterised by increased serum LDL-cholesterol and early CVD, autosomal dominant

Question 26

how do you get familial hypercholesterolemia (FH)?

Answer 26

mutations in the LDLR gene that encodes for the LDLR protein which reduces its function