The basis and practicalities of lipid treatment

Question 1

When risk factors coexist the effect is often exponential. What does this mean?

Answer 1

Their combined effect is greater than their individual effects.

Question 2

Describe the purpose of the framingham heart study

Answer 2

To identify the risk factors for CVD

Question 3

List the CVD risk factors discovered in the Framingham heart study

Answer 3

Major CVD risk factors:
-High blood pressure
-High blood cholesterol
-Smoking
-Obesity
-Diabetes
-Physical inactivity 
Also …
The effects of related factors such as blood triglyceride and HDL cholesterol levels, age, gender, and psychosocial issues.

Question 4

Describe some difficulties of the Framingham study

Answer 4

Based on North American data and, as a result, it is claimed that it overestimates cardiovascular risk in European populations.

It is also claimed that Framingham may underestimate cardiovascular risk in people with diabetes, South Asian men and those who are socially deprived.

Question 5

What is the aim of QRESEARCH?

Answer 5

To develop and maintain a high quality database of general practice derived data linked to secondary care data for use in ethical medical research.

Question 6

Describe QRISK

Answer 6

QRISK takes into account many of the traditional risk factors included in the Framingham algorithm (eg, age, sex, cholesterol-high density lipoprotein ratio, blood pressure, diabetes and smoking status).

However, it is based on UK data and includes additional risk factors, such as ethnicity, deprivation, blood pressure treatment and body mass index.

Question 7

What does a QRISK over 10 signify?

Answer 7

More than 10% risk of a CVD event occurring over the next 10 years
Indicates that primary prevention with lipid lowering therapy (such as statins) should be considered.

Question 8

What do healthy years mean?

Answer 8

Expected life without a heart attack or stroke

Question 9

List some unmodifiable risk factors

Answer 9

Age
Gender
Genetic factors

Question 10

List some modifiable risk factors of CVD

Answer 10

Sedentary lifestyle
Excess alcohol intake
Smoking 
Obesity
Diabetes
Hypertension
Excess lipids

Question 11

When should patients be referred to secondary care?

Answer 11

Full lipid profile taken
Do not use lipid cut off values alone
Combine the values with clinical findings and family history
Refer if TC is more than 7.5 mmol/L and the person has a family history of hypercholesterolemia or premature CVD
If TC is more than 9.0mmol/L, or the non-HDL-cholesterol concentration is more than 7.5mmol/L, refer the person to specialist care even in the absence of a first degree family history of premature coronary heart disease.

Question 12

Describe the primary prevention of CVD if the QRISK score is greater than 10

Answer 12

Start them on a statin

Atorvastatin 20mg

Question 13

Describe the secondary prevention of CVD with previous history of angina

Answer 13

Start them on a statin

Atorvastatin 80mg

Question 14

Why treat lipid disorders even if they are asymptomatic?

Answer 14

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

Question 15

What is the low density lipoprotein receptor and what does it do?

Answer 15

LDLR is a cell-surface receptor that recognizes 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 16

Describe the basic mechanism of a statin

Answer 16

Statins block the HMG-CoA reductase enzyme
Intracellular cholesterol level drops causing more production of LDL receptors which come to the surface and increase the influx of lipid particles. These particles are either used by the cell or stored in the liver.

Question 17

What is ezetimibe and what does it do?

Answer 17

Is a potent and selective inhibitor of absorption of cholesterol in the small bowel.
It reduces the contribution of dietary and biliary cholesterol and therefore reduces the flux of cholesteryl esters into Very Low Density Lipoprotein (VLDL) particles.

Question 18

What can bile acid sequestrants do?

Answer 18

Bind bile acids in the intestine, interrupting the enterohepatic circulation of bile.
Increased conversion of cholesterol into bile acids in liver
Increased LDLR activity decreases LDLC but can increase triglyceride as cholesterol synthesis increases

Question 19

What can bile acid sequestrants also cause?

Answer 19

Treatment limited by constipation and flatulence

Older resins cause oesophageal irritation

Question 20

Describe the action of fibrates

Answer 20

Binds nuclear PPAR (peroxisome proliferator-activated receptor)
Increase peripheral lipolysis (by activating lipoprotein lipase) and decrease hepatic triglyceride production.

Question 21

How does omega 3 work?

Answer 21

Inhibit lipogenesis and stimulate β-oxidation

Question 22

What is the outcome of using omega 3?

Answer 22

Reduced rate of secretion of very low density lipoprotein (VLDL) triglyceride (TG)

Question 23

Describe the PCSK9 receptor and the action of PCSK9 inhibitors

Answer 23

PCSK9 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 24

What are PCSK9 inhibitors?

Answer 24

Monoclonal antibodies to PCSK9

Question 25

List the 3 main patterns lipid profiles tend to form

Answer 25

Hypercholesterolaemia
Mixed hyperlipidaemia
Hypertriglyceridemia

Question 26

What is hypercholesterolaemia?

Answer 26

Seen in familial hypercholesterolaemia (FH) where total cholesterol levels may range between 7 and 20 mmol/L (average 9 mmol/L) in heterozygotes but are even higher in the rare homozygotes (15–30 mmol/L).

Question 27

What is mixed hyperlipidaemia?

Answer 27

(raised TC and LDL with raised TG, often low HDL). This pattern is often seen in patients with glucose intolerance and diabetes and arises from the increased production and reduced breakdown of triglyceride-rich lipoproteins.

Question 28

What is hypertriglyceridaemia?

Answer 28

Pure hypertriglyceridaemia is less common, may be familial and tending to cause harm through acute pancreatitis.

Question 29

Describe familial hypercholesterolaemia (FH)

Answer 29

Common genetic disordercharacterised by increased Serum LDL-Cholesterol and earlyCVD.Autosomal dominant

Mutations in theLDLRgene that encodes theLDLR protein which reduce its function. Can also have a mutation in ApoB or gain of function of PCSK9.

Question 30

List the clinical features of FH

Answer 30

Tendon xanthoma (common in the achilles tendon)
Corneal arcus below age 40

Question 31

Describe the treatment of FH

Answer 31

Low Saturated Fat Diet and exercise
Statins
Possible addition of cholesterol absorption inhibitor (ezetimibe)
Rarely resins/surgery/LDL apheresis
Anti–PCSK9
Involve patient self help group, offer DNA testing and get the family tested.

Question 32

What is the ideal total cholesterol level?

Answer 32

< 4

Question 33

What is the ideal HDL level?

Answer 33

> 1

Question 34

What is the ideal LDL level?

Answer 34

< 2

Question 35

What is the ideal triglyceride level?

Answer 35

< 1.7