1 / 29

Understanding Familial Hypercholesterolemia (FH) Guidelines and Management in the UK

This article delves into the key elements of the NICE FH Guideline and HEART UK work by Jonathan Morrell, exploring the prevalence and underdiagnosis of FH. It discusses the natural history of FH, the burden of high LDL-C in patients, and the efficacy of statins in reducing CHD risk. The text also covers how to identify people with FH through clinical signs and diagnostic criteria, emphasizing the importance of management strategies, including high-intensity statin therapy for adults and specialist care for children and young people. The article concludes with recommendations for ongoing assessment, monitoring, and cascade testing in FH patients.

bono
Télécharger la présentation

Understanding Familial Hypercholesterolemia (FH) Guidelines and Management in the UK

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

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. 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 Banker 31

  4. Prevalence of 10 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)

  5. Survey UK Lipid Clinics 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 HEARTUK 2008 Neil, et al BMJ 2000

  6. FH – natural history Slack, Lancet.1969;1380-2

  7. LDL- C Burden in FH patients 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

  8. Can LDL-C be lowered in FH patients? Hadfield et al 2007 3.3 mmol/l Overall ~ 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

  9. 20-59 year olds Pre Statin 1988–1992 > 2 fold Post Statin 1992–1999 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

  10. Cancer and Total Mortality Cancer 1980-91 (14) 1992-06 (76) Total 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 Secondary 1980-91 (25) 1992-06 (108) - 34% - 25% Primary 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)

  11. How should we identify people with FH?

  12. Clinical signs Eliza Parachute 1851

  13. Xanthelasma

  14. Corneal Arcus Lipidus

  15. Tendon Xanthomas in HeFH

  16. 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 10 relative (parent, sibling, child), or in 20 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 20 relative or below age 60 years in 10 relative or 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

  17. 20 Relatives of FH Proband LDL Cholesterol Distribution

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

  19. The LDL-receptor pathway 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

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

  21. NICE FH Guidelines

  22. Key priorities Diagnosis • 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

  23. Key priorities Management • 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

  24. Pathway implementation • Scotland • Wales • Northern Ireland • England

  25. NICE FH Guidelines A guideline not a directive

  26. 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

  27. HEART UK FH GIT • Raising profile NICE FH Guideline • www.heartuk.org.uk/fhgit • 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

  28. 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

More Related