Familial Hyperlipidaemia and Selected Dyslipidaemias

Question 1

Framingham heart study

Answer 1

1948 investigated epidemic of coronary heart disease in USA

Identify common factors that contribute to CVD

Question 2

Major CVD risk factors

Answer 2

High blood cholesterol
High blood pressure
Smoking
Obesity
Diabetes
Physical inactivity

Question 3

QRESEARCH

Answer 3

Over 24 million patients from 1300 GP in UK

Question 4

QRESEARCH aims

Answer 4

Develop and maintain high quality database of GP derived data linked to secondary care data for us in ethical medical research

Question 5

QRISK

Answer 5

TAkes into account risk factors in framingham algorithm

Additional

• ethnicity
• deprivation
• blood pressure treatment
• BMI

Question 6

QRISK of 10

Answer 6

Indicates that primary prevention with lipid lowering therapy should be considered

Question 7

Healthy years

Answer 7

Expected life without a heart attack or stroke

Question 8

Heart age

Answer 8

Compared to a person of the same age, gender, ethnicity with optimal risk factor

Question 9

Modifiable risk factors

Answer 9

Smoking
Obesity
Sedentary lifestyle
Diabetes
High cholesterol
Hypertension
Excess alcohol intake

Question 10

Un-modifiable risk factors

Answer 10

Age
Gender
Genetic factors

Question 11

Primary prevention

Answer 11

No previous history of

• angina
• MI
• coronary artery procedures

Statin
- atorvastatin 20mg

Question 12

Secondary prevention

Answer 12

With previous history of

• angina
• MI
• coronary artery procedure

Statin
- atorvastatin 80mg

Question 13

Why treat lipid disorders?

Answer 13

Reduce atherosclerotic process

Prevent pancreatitis (associated with grossly increased serum triglyceride)

Question 14

Low density lipoprotein receptor

Answer 14

Recognises ApoB-100 embedded in phospholipid outer layer of LDL particles

Majority on liver

Question 15

Exetimibe

Answer 15

Potent and selective inhibitor of absorption of cholesterol in small bowel

Reduces flux of cholesterol esters into VLDL

10mg/day induce 20% reduction in LDLC and 8% reduction in TG

Question 16

Bile acid sequestrants

Answer 16

Bind bile acids in intestine, interrupt enterohepatic circulation of bile

Increased conversion of cholesterol to bile acids in liver

Increased LDLR activity decreases LDLC

Limited by constipation and flatulence

Older resins cause oesophageal irritation

Question 17

Fibrates

Answer 17

Bind nuclear PPAR

Increase peripheral lipolysis and decrease hepatic triglyceride production

Reduce triglyceride by 25-50%, raise HDLC by 15-25%

Question 18

Omega 3 (fish oils)

Answer 18

Inhibit lipogenesis and stimulate b-oxidation

Reduced rate of secretion of VLDL

Question 19

PCSK9 inhibitors

Answer 19

New class of lipid lowering medications

Bimonthly subcutaneous injections

Monoclonal antibodies to PCSK9

Question 20

PCSK9

Answer 20

Binding protein

Expressed primarily in hepatocytes

Promotes LDLR degradation

Question 21

Hypercholesterolaemia

Answer 21

Raised TC and LDLC

Total cholesterol levels may range between 7 and 20 mmol/L

Higher in rare homozygous

Question 22

Mixed hyperlipidaemia

Answer 22

Raised TC and LDLC with raised TG and often low HDLC

Seen in patients with glucose intolerance and diabetes

Arise from production and reduced breakdown of triglyceride rich lipoproteins

Question 23

Hypertriglyceridaemia

Answer 23

Pure is less common

May be familial

Harm through acute pancreatitis

Question 24

Familial hypercholesterolaemia

Answer 24

Common genetic disorder by increases LDL and early CVD

Autosomal dominant LDLR gene

Few cases mutation in ApoB or gain function mutation in PCSK9

Wide range of age at first CV event in heterozygous

Question 25

Clinical presentation of FH

Answer 25

Tendon xanthoma

Corneal arcus

Deposits of cholesterol from LDL on skin

Question 26

Treatment of FH

Answer 26

Low saturated fat diet

Statins

Addition of cholesterol absorption inhibitor

Rarely resins/ surgery/ LDL apheresis

Anti PCSK9