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Key elements of the NICE FH Guideline and the work of the HEART UK FH GIT Jonathan Morrell Hastings.

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Presentation on theme: "Key elements of the NICE FH Guideline and the work of the HEART UK FH GIT Jonathan Morrell Hastings."— Presentation transcript:

1 Key elements of the NICE FH Guideline and the work of the HEART UK FH GIT Jonathan Morrell Hastings

2 National Health Checks 2009

3 Banker 31 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 TC 9.8 HDL 1.4 TG 1.1

4

5 Prevalence of 1 0 Dyslipidaemias Hypercholesterolaemia Polygenic (common, 1 in 50) Heterozygous FH (HeFH)(approx. 1 in 500) Homozygous FH (HoFH)(approx. 1 in 1,000,000) Hypertriglyceridaemia 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)

6 It is Common - Frequency FH ~1/ ,000 in UK It is underdiagnosed < 15,000 known, particularly in the < 35 years group (600/14,000 children) How Common is FH ? Same as childhood diabetes Survey UK Lipid Clinics Missing >85% of predicted Marks, et al 2004 HEARTUK 2008 Neil, et al BMJ 2000

7 FH – natural history Age (years) ♂ % CHD ♀ % CHD < Slack, Lancet.1969;1380-2

8 LDL- C Burden in FH patients By 45yrs FH patient has accumulated LDL-C exposure of non- FH 70yr old, explaining high CHD risk and need for aggressive lipid-lowering FH patients have high LDL-C from Birth  high LDL-C BURDEN Like smoking pack-years LDL - Burden = LDL-C level x years exposure Starr et al 2008

9 Can LDL-C be lowered in FH patients? Low potency (cheap) Simvastatin 40 is inadequate for >95% FH patients Combination therapy may be needed to achieve target 6.7 mmol/l 3.3 mmol/l Overall ~ 50% reduction n = 249 Hadfield et al 2007 But 34% > 4.0mmol/l and 12% > 5.0mmol/l

10 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 Post Statin 1992–1999 Pre Statin 1988–1992 > 2 fold year olds

11 Current Life Expectancy in treated FH patients Neil et al E Heart J 2008 Secondary (25) (108) Based on 2766 (1456 M/1310 F) DFH + PFH patients. 190 CHD and 90 cancer deaths (37727 person years follow-up) Primary (12) (45) - 25% CHD Mortality in those with/without CHD - 48% - 34% Cancer (14) (76) Total (55) (315) Cancer and Total Mortality - 29% Age years

12 How should we identify people with FH?

13 Clinical signs Eliza Parachute 1851

14 Xanthelasma

15 Corneal Arcus Lipidus

16 Tendon Xanthomas in HeFH

17 Simon Broome criteria 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) plus  tendon xanthomas in patient, or in 1 0 relative (parent, sibling, child), or in 2 0 relative (grandparent, uncle, aunt) or  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 2 0 relative or below age 60 years in 1 0 relative or  family history of raised TC >7.5 mmol/l in adult 1 0 or 2 0 relative or > 6.7 mmol/l in child or sibling <16y

18 2 0 Relatives of FH Proband LDL Cholesterol Distribution

19 The LDL receptor Brown and Goldstein identified autosomal dominant LDLR defect in FH fibroblasts in 1974

20 The LDL-receptor pathway Soutar, A Nat Clin Pract Cardiovasc Med 2006; 4:214 LDL receptor defect.80-95% of cases PCSK9 defect. Gain and loss of function mutations. 2% ApoB3500 defects (binding ligand). 3-10%. Less severe phenotype Autosomal recessive hypercholesterolaemia. Rare

21 Leigh et al Annals Hum Genet 2008 UCL 2008 Database of published LDLR mutations W-Wide n = 949 UK n = 208 * * p = 0.01 Single base changes + small dels 1066 different causes of FH reported world-wide

22 NICE FH Guidelines

23 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 Key priorities Diagnosis

24 Key priorities 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. 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 Identifying people with FH using cascade testing Ongoing assessment and monitoring Management

25 Pathway implementation Scotland Wales Northern Ireland England

26 NICE FH Guidelines A guideline not a directive

27 HEART UK FH 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

28 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

29 HEART UK FH GIT 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


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