FAMILIAL HYPERCHOLESTEROLE

MIA

 President

 Belgian Association of Patients suffering from Familial Hypercholesterolemia

 Director

 Lipid Clinic and Cardiovascular Prevention

(Internal Medicine)

 Center for Medicial Research.

Olivier Descamps, MD, PhD

Population: 3 wrong beliefs about cholesterol !

«Cholesterol ? » = Adult-Problem = Food-Problem = Drug-Problem

Clinical  Case  

48-yr-old man … In coronary care unit Admitted for myocardial

Infarctus

(mg/dl) Total Cholesterol: 428 LDL-Cholesterol : 360 Triglycerides : 137 HDL-Cholesterol : 42 Equilibrated diet and physical activity

Death 79 yrs No CHD LDL 152 mg/dL

Age 78 yrs CHD 58 yrs LDL 296 mg/dL

Age 48 yrs CHD 48 yrs LDL 360 mg/dL

Age 47 yrs No CHD LDL 96 mg/dL

Age 50 yrs No CHD LDL 131 mg/dL

Index case: start of cascade screening

Age 18 yrs LDL 88 mg/dL

Age 8 yrs LDL 224 mg/dL

Age 15 yrs LDL 244 mg/dL

FH FH

FH

FH

Man Woman

High suspicion of Familial Hypercholesterolemia

Familial  Hypercholesterolemia  (FH)    

Doctors’ 3 wrong beliefs about familial hypercholesterolemia !

«FH ? » = A genetic diagnosis !? = We have time !? = Rare !?

Familial  Hypercholesterolemia  Gene6c  BUT  its  is  a  Clinical  Diagnosis  !    

DUTCH LIPID CLINC DIAGNOSTIC CRITERIA > 8 points : Definite FH 6 - 8 points : Probable FH 3 – 5 points : Possible FH

DUTCH LIPID CLINC DIAGNOSTIC CRITERIA > 8 points : Definite FH 6 - 8 points : Probable FH 3 – 5 points : Possible FH

Normal

ATT > 5,8 : FH patient Descamps O. Atherosclerosis 2002. 157: 514-518

Familial  Hypercholesterolemia  Gene6c  BUT  its  is  a  Clinical  Diagnosis  !    

•  Premature  Cardiovascular  Disease  (CV):  By  age  of  60  years,      50%  FH  men  and  30%  FH  women  develop  CHD  

Familial  Hypercholesterolemia  (FH)  We  don’t  have  6me  !    

De Groot E et al. Circulation 2004: 109:1133

Carotid Ultrasonography

Intima Media

Familial  Hypercholesterolemia  (FH)  We  don’t  have  6me  !    

Le c

hole

stér

ol s

e dé

pose

da

ns la

par

oi a

rtér

ielle

35 ans 45 ans 60 ans 70 ans

Age (années)10 20 30 40 50 60

Zone critique (symptomatique)

HF Non traitée

HH traitée tardivement

HF traité précocement

Age de la première complication:

Zone silencieuse(asymptomatique)

Population générale

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Familial  Hypercholesterolemia  (FH)  We  don’t  have  6me  !    

Vermissen et al. BMJ 2008; 337: a2423

Familial  Hypercholesterolemia  (FH)  Treat  …  to  reduce  cardiovascular  disease  (CVD)      

Comparison  of  CVD  occurrence  In  subjects  treated  from  childhood  versus  their  FH  parents  treated  from  adulthood.  

Comparison  of  CVD  occurrence  In  treated  FH  pa<ents      Versus  untreated  FH  pa<ents  

Wiegman et al. EHJ 2015; May 25

Familial  Hypercholesterolemia  (FH)  :  Correct  as  Intensively  and  as  early  as  possible  In  addi<on  to  lifestyle/dietary  counselling,  prescribe      

     Children  (8-­‐10  yrs)      Adults                              .    Sta<n                  Low  dose      Max  potent  sta<n  dose  Eze<mibe              If  necessary            In  most  pa<ents            Ideal  LDL-­‐C  targets                <135  mg/dL  <100mg/dL    

           <70mg/dL  if  CHD/diab  

New treatment for FH ! Anti PCSK9 Antibodies 1-2 x / Month - Praluent (SANOFI) - Repatha (AMGEN)

45% LDL reduction ! 80% on target !

732 HeFH patients (100% statin and 55 % on ezetimibe

134 - 144 mg/dL

66 - 76 mg/dL

148 - 153 mg/dL

Familial  Hypercholesterolemia  (FH)  :  Correct  as  Intensively  and  as  early  as  possible  

•  1/400  =  25,000  Belgians    –  GHHAINAUT  PROJECT  !  

• Gene6c  Hypercholesterolemia  In  Hainaut  (1997)  

•  50%  Transmission  =  very  frequent  in  families  !  –  KOALA-­‐LOU  PROJECT  !    

• Cholesterol  à  La  Louvière  (2013)  

Familial  Hypercholesterolemia  (FH)  Not  Rare  at  All  !!!    

GHHAINAUT PROJECT (1996) Genetic Hypercholesterolemia in Hainaut

 OBJECTIVE. Demonstrate the existence of FH amongst the patients of General Practitioners (GP).

 METHODS. During a 1 year period, GP were asked to collect blood in their patients with high cholesterol and family history

Patients with Cholesterol > 300 mg/dL and Family history of early CVD Data (anonymous)

Suspected relatives

ê

Funding : Ligue Cardiologique Belge Hôpital de Jolimont, Pharma (MSD)

GHHAINAUT

GHHAINAUT PROJECT (1996) Genetic Hypercholesterolemia in Hainaut

 RESULTS  (in 1 year):

CONCLUSION. During this limited period of time, -  182 patients were suspected of FH by motivated GP -  1/3 (63) were confirmed for having FH. -  105 (63 + 42) diagnosis of FH

91 Phase 1. (Index patients) 182 63

Phase 2. (Relatives)

ê

26 54 42

GHHAINAUT

KOALA-LOU PROJECT : CASCADE SCREENING IN FAMILIES OF FH PATIENTS LIVING IN LA LOUVIERE / MANAGE

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 OBJECTIVE : Identify all relatives with in the family of patients already for FH diagnosed (by genetic test)

 METHODS. « Flying nurse » + Cascade Screening + Genetic/Clinic

Funding : Mutualité Chrétienne, Ligue Cardiologique Belge, PHARMA (MSD, ASTRA ZENECA, AMGEN, SANOFI)

FH Patients living in La Louvière or

Manage N= 88

Cholesterol (& genetic) tests

DNA FH Diagnosis (since

1995) N = 744 éê ê

 RESULTS

CONCLUSION. 207 NEW FH DIAGNOSIS from 69 patients (3 for 1) - Amongst these 207, - 56% ignored they had high cholesterol (Surprise !)

- Positive reaction : release of frustration ! - In these cities: 75% of the expected number (=250 if 1/400) are identified

Index Patients with FH in LaLou-Mana

88 314 69 643 207 +

= 181

49 < 25 years)

KOALA-LOU PROJECT : CASCADE SCREENING IN FAMILIES OF FH PATIENTS LIVING IN LA LOUVIERE / MANAGE

93

SITUATION IN BELGIUM ?

 Categorie B (général) : ­  Histoire Personelle de maladie cardiovasculaire (CV) ­  OU haut risque CV Risk (SCORE ≥ 5%; dans le rouge !)

 Categorie A (FH) ­  Total cholestérol > 300 mg/dL ­  PLUS une de ces conditions ­  Maladie cardiovasculaire précoce chez parent du 1° degré ( père/

frère <55 ans ; mère/soeur < 65 ans) ­  Un test génétique démonstrant une mutation sur LDL écepteur

Statin Reimbursement for FH in Belgium

Age Categories

Expected with FH based on -  the age distribution of the

belgian population -  a prevalence of 1/400 of FH (N= 25000) Observed with Catégory A reimbursement for statin and combination (statin + ezetimibe) (N=12185)

SITUATION IN BELGIUM PHARMANET DATA (INAMI 2014)

Number of patients by age class

CONCLUSION. Patients in category A are treated long after cardiovascular complications usually have occurred in FH …. Too late !

Conclusion. L’hypercholestérolémie Familiale … Un paradoxe ?

v  FH est fréquente (25000 Belges)

v  Maladies Cardio-Vasc précoces sont évitables si cholestérol traité avant 20 ans

v  Mal génétique doit être dépistée en famille

Mais Peu sont v  « Aware »

v  Identifié !

v  Traité à temps !

v  Recherché dans famille et l’enfance

è ATTENTION è CONSCIENTISATI

ON

Internet website WWW.BELCHOL.BE

Newspaper articles Press communication

Press conference

- BELGIAN FH PATIENTS ASSOCIATION -

Parliament conference

Conclusion. L’hypercholestérolémie Familiale … Un paradoxe ?

v  FH est fréquente (25000 Belges)

v  Mal Cardio-Vasc précoce sont évitables si cholestérol traité avant 20 ans

v  Mal génétique doit être dépistée en famille

Mais Peu sont v  « Aware »

v  Identifié !

v  Traité à temps !

v  Recherché dans famille et l’enfance

è ATTENTION of ALL è ALERT on LAB protocol è REIMBURSEMENT ! è THINK FAMILY

General Practitioners Pharmacists Specialists

+ Government INAMI/RIZIV MUTUALITY +

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Total cholestérol = 400 mg/dL ? Prof.  Leiv  Ose    Paediatrician    at  University  of  Oslo  

Thank You !

First meeting of Belgian FH patients at the Jolimont Hospital

Homozygotes  FH  

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•  Very rare : 1/1000000 •  Both parents have HeFH •  Very high LDL-C (children > 500mg/dL) •  Xanthomas in the first decade. •  CV complication in the first/second decade

(CHD, cardiac valvulopathy, …).