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Key elements of the NICE FH Guideline and the work of the HEART UK FH GIT. Jonathan Morrell Hastings. National Health Checks 2009. Asymptomatic Non-smoker 124/62 Father died MI 49, paternal uncle angina 52, paternal grandfather sudden death 54 2 sons aged 6 and 3 2 brothers and 1 sister.

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Key elements of the nice fh guideline and the work of the heart uk fh git

Key elements of the NICE FH Guideline and the work of the HEART UK FH GIT

Jonathan Morrell


Banker 31

Asymptomatic HEART UK FH GIT



Father died MI 49, paternal uncle angina 52, paternal grandfather sudden death 54

2 sons aged 6 and 3

2 brothers and 1 sister

TC 9.8 HDL 1.4 TG 1.1

Banker 31

Prevalence of 1 0 dyslipidaemias
Prevalence of 1 HEART UK FH GIT0 Dyslipidaemias


Polygenic (common, 1 in 50)

Heterozygous FH (HeFH) (approx. 1 in 500)

Homozygous FH (HoFH) (approx. 1 in 1,000,000)


Familial lipoprotein lipase deficiency (approx. 1 in 1,000,000)

Familial apolipoprotein CII deficiency (approx. 1 in 1,000,000)

Familial hypertriglyceridaemia (approx. 1 in 100)

Combined Hyperlipidaemia

Familial combined hyperlipidaemia (approx. 1 in 100)

Familial type III hyperlipidaemia (approx. 1 in 5,000)

Survey UK Lipid Clinics HEART UK FH GIT

Missing >85%

of predicted

  • How Common is FH ?

  • It is Common - Frequency FH ~1/500 120,000 in UK

  • It is underdiagnosed < 15,000 known, particularly in the < 35 years group (600/14,000 children)

Same as childhood diabetes

Marks, et al 2004


Neil, et al BMJ 2000

Fh natural history
FH – natural history HEART UK FH GIT

Slack, Lancet.1969;1380-2

LDL- C Burden in FH patients HEART UK FH GIT

Starr et al 2008

FH patients have high LDL-C from Birth  high LDL-C BURDEN

LDL - Burden =

LDL-C level x

years exposure

Like smoking pack-years

By 45yrs FH patient has accumulated LDL-C exposure of non- FH 70yr old, explaining high CHD risk and need for aggressive lipid-lowering

Can LDL-C be lowered in FH patients? HEART UK FH GIT

Hadfield et al 2007

3.3 mmol/l


~ 50% reduction

6.7 mmol/l

But 34% > 4.0mmol/l

and 12% > 5.0mmol/l

n = 249

Low potency (cheap) Simvastatin 40 is inadequate for >95% FH patients

Combination therapy may be needed to achieve target

20-59 year olds HEART UK FH GIT

Pre Statin


> 2 fold

Post Statin


Statins reduce CHD in FH

Simon Broome UK-FH Register papers, BMJ 1991, Athero 1999,

8.1 = >23 yrs reduction

in life expectancy

~ 9 years gained by statins

Cancer and Total Mortality HEART UK FH GIT


1980-91 (14)

1992-06 (76)


1980-91 (55)

1992-06 (315)

Current Life Expectancy in treated FH patients

Neil et al E Heart J 2008

Age 20-79 years

CHD Mortality in those with/without CHD


1980-91 (25)

1992-06 (108)

- 34%

- 25%


1980-91 (12)

1992-06 (45)

- 48%

- 29%

Based on 2766 (1456 M/1310 F) DFH + PFH patients. 190 CHD and 90 cancer deaths (37727 person years follow-up)

Clinical signs
Clinical signs HEART UK FH GIT

Eliza Parachute 1851

Xanthelasma HEART UK FH GIT

Corneal arcus lipidus
Corneal Arcus Lipidus HEART UK FH GIT

Tendon Xanthomas in HeFH HEART UK FH GIT

Simon broome criteria
Simon Broome criteria HEART UK FH GIT

Definite FH:

TC > 6.7 mmol/l or LDL-C >4.0 mmol/l (child <16y)

or TC > 7.5 mmol/l or LDL-C >4.9 mmol/l (adult)

(levels either pre-treatment or highest on treatment)


tendon xanthomas in patient, or in 10 relative (parent, sibling, child), or in 20 relative (grandparent, uncle, aunt)


DNA-based evidence of an LDL receptor mutation, familial defective apo B-100, or a PCSK9 mutation.

Possible FH is defined as above lipids plus one of:

family history of myocardial infarction: below age of 50 years in 20 relative or below age 60 years in 10 relative


family history of raised TC >7.5 mmol/l in adult 10 or 20 relative or > 6.7 mmol/l in child or sibling <16y

2 0 relatives of fh proband ldl cholesterol distribution
2 HEART UK FH GIT0 Relatives of FH Proband LDL Cholesterol Distribution

The ldl receptor
The LDL receptor HEART UK FH GIT

Brown and Goldstein

identified autosomal

dominant LDLR defect in FH

fibroblasts in 1974

The ldl receptor pathway
The LDL-receptor pathway HEART UK FH GIT

ApoB3500 defects (binding ligand). 3-10%. Less severe phenotype

LDL receptor defect.80-95% of cases

Autosomal recessive hypercholesterolaemia. Rare

PCSK9 defect. Gain and loss of function mutations. 2%

Soutar, A Nat Clin Pract Cardiovasc Med 2006; 4:214

UCL 2008 Database of published LDLR mutations HEART UK FH GIT

Leigh et al Annals Hum Genet 2008

1066 different causes of FH reported world-wide

Single base changes

+ small dels

W-Wide n = 949

UK n = 208


*p = 0.01

Nice fh guidelines


  • Use the Simon Broome criteria to diagnose FH

  • All individuals should be offered a DNA test to confirm the diagnosis and to assist in cascade testing of relatives

  • CHD risk estimation tools such as those based on the Framingham algorithm should not be used because people with FH are already at a high risk of CHD.

  • In children at risk of FH because of one affected parent the following diagnostic tests should be carried out by age of 10 years :

  • - a DNA test if the family mutation is known

    • - LDL-C measurement if mutation not known


  • Adults - Prescribe a high-intensity statin to achieve a reduction in LDL-C of > 50% from baseline (ie, before treatment).

  • Children/young people – Should be seen by a specialist in an appropriate setting, and using clinical judgement, statin therapy considered by age 10

  • All people with FH should be offered an annual regular structured review

Ongoing assessment and monitoring

  • Cascade testing - combination of DNA testing and LDL-C levels is recommended to identify affected relatives of those with a clinical FH.

  • The use of a nationwide, family-based, follow-up system is recommended to enable comprehensive identification of people affected by FH.

Identifying people with FH using cascade testing

Pathway implementation
Pathway implementation HEART UK FH GIT

  • Scotland

  • Wales

  • Northern Ireland

  • England

Nice fh guidelines1

A guideline not a directive

Heart uk fh guideline implementation team
HEART UK HEART UK FH GITFH Guideline Implementation Team

  • Identify challenges and risks in the implementation of the NICE FH Guideline

  • Propose solutions and incorporate them into a FH Guideline Implementation toolkit

  • Support commissioning and delivery of services

Heart uk fh git

  • Raising profile NICE FH Guideline


  • Influencing commissioning pathway

  • DH, primary care commissioning, RCGP, CV networks and SHAs

  • Support from BHF, PCCS and BCS

  • Identify service gaps (RCP audit)

  • Liaison with NICE

  • Toolkit development

Heart uk fh git1

  • Anniversary campaign

  • SHA events

  • Consensus meeting

  • Finalise and launch toolkit

  • Patient campaign

  • Lobbying (parliamentary and SHAs)

  • GP survey

  • FOI requests to PCTs

  • Supporting commissioning bids