Familial hyperlipidaemia

Question 1

The Framingham Risk Score is a gender-specific algorithm used to estimate the 10-year cardiovascular risk of an individual. What are its shortcomings?

Answer 1

Based on N.American data

Underestimates the CVD risk in people with diabetes, S.Asian men and those socially deprived

Question 2

What are the advantages of using Q-research risk calculator over the Framingham Risk score?

Answer 2

Based on UK data
Considers more factors (age, sec, CHDL, BP, diabetes, smoking)
If QRisk2>10% = prevention needed
NICE recommended
Basis of Joint British Societies (JBS) for the prevention of CVD

Question 3

Suggest some modifiable risk factors for CHD

Answer 3

Smoking
Obesity
Sedentary lifestyle
Diabetes
High cholesterol or abnormal blood lipids
Hypertension
Excess alcohol intake

Question 4

Suggest some unmodifiable risk factors for CHD

Answer 4

Age (>50)
Gender
Genetic factors

Question 5

When is the use of Risk contraindicated?

Answer 5

In those who have CVD, Type 1 diabetes, low GFR, familial hypercholesterolaemia

Question 6

Why might lipid disorders be difficult to diagnose?

What does treatment aim to achieve?

Answer 6

Asymptomatic

Treatment decreases atherosclerotic process and prevent pancreatitis (associated with high serum triglyceride)

Question 7

In the management of lipid disorders, how do bile acid sequestrates (Resins) work?

Answer 7

Bind bile acids in intestine, interrupting the enterohepatic circulation of bile

This increases conversion of cholesterol -> bile acid in liver

This increases LDL receptor activity which decreases LDL-C BUT it can increases triglyceride as cholesterol synthesis increases

Side effects include constipation, flatulence, oesophageal irritation

Question 8

What effects do omega 3 (fish oils) have on metabolism?

Answer 8

Inhibit lipogenesis and stimulate B-oxidation

Decrease rate of secretion of VLDL and TG

Question 9

In the management of lipid disorders, what do PCSK9 inhibitors do?

Answer 9

PCSK9= binding protein expressed primarily on hepatocytes

It binds to LDL receptors and promotes degradation. Blocking this increases availability of LDL receptors to remove LDL-C from serum

NEW

Administered bimonthly via subcutaneous injections
Monoclonal antibody to PCSK9

Question 10

Describe three lipid disorders

Answer 10

HYPRCHOLESTEROLAEMIA
Raised LDL-C and TC
Seen in familial HC (Heterozygous up to 9mmol/L, Homozygous up to 30mmol/L)

MIXED HYPERLIPIDAEMIA
Glucose intolerant patients and diabetics
Reduced breakdown of TG-rich lipoproteins
Raised TC, TG and LDL-K with low HDL-C

Hypertriglyceridaemia
less common
may be familial
tending to cause harm through acute pancreatitis.

Question 11

Describe the epidemiology,aetiology and clinical presentation of familial hyperlipidaemia

Answer 11

Common: 1/200-250
Increased serum LDL-C and early CVD
Autosomal dominant: mutation in LDL receptor gene
Approx 3% will have mutation in ApoB
CV even in heterozygous FH

Clinical presentation: Tendon xanthoma, corneal arcus, bumps on skin (deposits of cholesterol derived from LDL-C)

Question 12

Generally what would the fasting stats of a patient with heterozygous familial hyperlipidaemia look like

Answer 12

High cholesterol (>5mmol/L)
High LDL-C (>3mmol/L)
High non-HDL-C (>2.8 mmol/L)

Creatinine, thyroid, liver, glucose and albumin are normal

Question 13

How is FH treated?

Answer 13

Decrease saturated fats in diet
Exercise
Statins
Cholesterol absorption inhibitor (Ezetimbe)
Resins (RARE)
Anti-PCSK9
Patient self help, DNA testing