1. Developing FH services in South West and South East London Anthony S. Wierzbicki Consultant in metabolic medicine/chemical pathology Guy’s & St Thomas’ Hospitals London

2. Statement of Interests Member: HEART-Uk FH guideline implementation group Ex-Chairman Medical Scientific & Research Committee HEART-UK (2002-8) Member NICE-FH guideline group (2007-8) Member: SE London cardiac network Clinical Lead : Lipid & Obesity services GSTT

3. NHS Vascular risk programme briefing packs ; ww.doh.gov.uk The NHS (Vascular) Health Check NHS Health Check

4. Lay knowledge of FH in families (Australia) Maxwell SJ et al; Gen Test Mol Biomarker 2009; 13 : 301-6

5. LDL-C distributions in FH and the general population Starr BA et al; CCLM 2008; 46 : 791-803

6. Changing mortality of CHD in the last century Definite FH (V408M) Possible FH (V408M) Population rate Based on Stallones RA; Sci Am 243; (11) 43 Sijbrands EJG et al; BMJ 2001; 322: 1019

7. FH Pathway : NICE CG71 TC ≥ 7.5 with family history of CVD (1st ° relative CVD < 60 yrs old) = High suspicion group (about 2% of the pop) 1º CARE (NHS Health Check) Referred for assessment with a Primary Care Professional with special interest in CVD - (GPSI or Nurse Practitioner or SpR) & LPA exclusion tests to track family heart disease. 50% will be referred back to GP (non FH) to continue with normal CVD risk assessment. 50% will be referred up into 2º CARE (as possible FH) Cholesterol ≥7.5 Lab. Notification to GP recheck full fasting lipids & FPG & Rule our 2 nd causes High Suspicion Group to be filtered (~1% of the pop) Simon Broome criteria SB(+) DNA / Genetic test FH Negative FH (+) or clinical (+) DNA (-) but high suspicion Managed pathway back to 1 º CARE SB (-) No DNA / Genetic test Long Term Management i.e. FH Positive/ Negative but high suspicion Info provided for relatives for Cascade Testing (see separate pathway) Long term management of children <16 in paediatric setting with transition protocol to adult services 1/3 = Stabilised. respond to treatment immediately referred back to 1º CARE for yearly monitoring with a plan and a formal 5yr review to be considered for referral 1/3 Problematic need longer before being stabilised 1/3 = Complex need continual 2º CARE involvement. Shared Care + Register of FH (kept in 2º CARE)

8. FH tendon xanthomata N=348 (52% male) CHD (+) 9.5% Tendon xanthomata (physical): 27.6% TX(+) by ultrasound: 56.6% TX(-) both methods: 39.4% Determined by LDL-C, age, gender (19% variance) Jarauta E et al; Atherosclerosis 2008; 204: 345-7

9. FH: tendon xanthomata & risk Civiera F et al ; ATVB 2005; 25: 1960-5 Oosterveer DM et al ; Atherosclerosis 2009 in press

10. What Is Carotid Intima Media Thickness (CIMT)? Normal and Diseased Arterial Histology Mean CIMT 1.174 mm

11. Tendon xanthomata & cIMT Jarauta E et al; Atherosclerosis 2008; 204: 345-7

12. cIMT in FH and controls deGroot E et al; Circulation 2004; 109 suppl III : 33-38 FH Controls

13. FH Pathway TC ≥ 7.5 with family history of CVD (1st ° relative CVD < 60 yrs old) or TC ≥ 9 no family history = High suspicion group (about 2% of the pop) 1º CARE (NHS Health Check) Referred for assessment with a Primary Care Professional with special interest in CVD - (GPSI or Nurse Practitioner or SpR) & LPA exclusion tests to track family heart disease. 50% will be referred back to GP (non FH) to continue with normal CVD risk assessment. 50% will be referred up into 2º CARE (as possible FH) Cholesterol ≥7.5 Lab. Notification to GP recheck full fasting lipids & FPG & Rule our 2 nd causes High Suspicion Group to be filtered (~1% of the pop) & cIMT screening out (eventually used at 1º CARE stage) DNA / Genetic test FH Negative FH Positive/ Negative but high suspicion Managed pathway back to 1 º CARE Simon B Criteria No DNA / Genetic test Long Term Management i.e. FH Positive/ Negative but high suspicion Info provided for relatives for Cascade Testing (see separate pathway) Long term management of children <16 in paediatric setting with transition protocol to adult services 1/3 = Stabilised. respond to treatment immediately referred back to 1º CARE for yearly monitoring with a plan and a formal 5yr review to be considered for referral 1/3 Problematic need longer before being stabilised 1/3 = Complex need continual 2º CARE involvement. Shared Care + Register of FH (kept in 2º CARE)

14. Cascade Testing Pathway ▪Random Cholesterol ▪DNA test for known family mutation (mouth swab) FH Index Individual DNA +ve. DNA -ve = Not FH OR Cholesterol ≥ 6.5 (treat now) OR Cholesterol ≤6.5 DNA +ve Cholesterol ≥ 6.5 Letter to give to relatives 1 st 2 nd 3 rd degree. Relatives seen in 1º CARE: own GP or Professional with Special Interest, with counselling skills/for content DNA +ve But Cholesterol ≤6.5 Long-Term Management 2 º CARE /shared care Refer back to 1º CARE Referral to normal CVD risk assessment: 5yr call/recall Specialist Review not normal CVD Risk Assessment

15. Communicating FH test results N=430 telephone interview (75% agreed) 93% wished to know result - 33% found anonymity of index case unacceptable 91% want to be told by relative Women aged 18-54 77% want to be told by health clinic 93% want to have children screened Maxwell SJ et al; Gen Test Mol Biomarker 2009; 13 : 301-6

16. Response to screening results Maxwell SJ et al; Gen Test Mol Biomarker 2009; 13 : 301-6

17. Information and contact methods Maxwell SJ et al; Gen Test Mol Biomarker 2009; 13 : 301-6

18. Cascade Testing Pathway ▪Random Cholesterol ▪DNA test for known family mutation (mouth swab) FH Index Individual DNA +ve. DNA -ve = Not FH OR Cholesterol ≥ 6.5 (treat now) OR Cholesterol ≤6.5 DNA +ve Cholesterol ≥ 6.5 Letter to give to relatives 1 st 2 nd 3 rd degree. Relatives seen in 1º CARE: own GP or Professional with Special Interest, with counselling skills/for content DNA +ve But Cholesterol ≤6.5 Long-Term Management 2 º CARE /shared care Refer back to 1º CARE Referral to normal CVD risk assessment: 5yr call/recall Specialist Review not normal CVD Risk Assessment

19. Assumptions on FH prevalences CriteriaGPNPCT 100%12,100290400 FHx IHD< 608%96823232 Screenees TC/IHD/Rx/Dx 3%3638712 FH Definite0.20%20480 FH Possible (hi)0.40%471128 FH possible (lo)2%2165184 Baseline populationPCT 300,000100% TC> 7.53000010.00% FHx IHD30% FHx IHD <60300010% cIMT > 0.8mm @40150050% Real FH6000.02% Known = 15%90 Unknown510 Gray J et al; Heart 2008; 94: 754-8

20. Potential costs ItemCost (£)Number1 year Polyclinic review£5060030000 Lipid clinic review£20030060000 CIMT£5040020000 Lp(a)£126007200 Genotyping- index£25020050000 Genotyping family£5040020000 Nurse grade 7 0.5WTE£40,00040000 £187200 ItemCostNumber1 year Polyclinic review£50113356640 Lipid clinic review£20032264320 CIMT£5032216080 Lp(a)£123223859 Genotyping- index£4009638400 Genotyping family£6035521312 Nurse grade 7 0.5WTE£40,00040000 £240611 Model 1 Prevalences: Gray et alModle 2 Prevalences: Assumed