01. Descamps O. Familial Hypercholesterolemia in Belgium

FAMILIAL
HYPERCHOLESTEROLE
MIA
Olivier Descamps, MD, PhD
 President
 Director
 Belgian Association of Patients
suffering from Familial
Hypercholesterolemia
 Lipid Clinic and Cardiovascular
Prevention
(Internal Medicine)
 Center for Medicial Research.
Population: 3 wrong beliefs about
cholesterol !
«Cholesterol ?
»
= Adult-Problem
= Food-Problem
= Drug-Problem
Clinical Case Man
Woman
Index case:
start of
cascade
screening
FH
48-yr-old man …
In coronary care unit
Admitted for myocardial
Infarctus
Total Cholesterol:
LDL-Cholesterol :
Triglycerides :
HDL-Cholesterol :
(mg/dl)
428
360
137
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
FH
Age 50 yrs
No CHD
LDL 131 mg/dL
Age 48 yrs
CHD 48 yrs
LDL 360 mg/dL
Age 47 yrs
No CHD
LDL 96 mg/dL
FH
Age 18 yrs
LDL 88 mg/dL
Age 15 yrs
LDL 244 mg/dL
FH
Age 8 yrs
LDL 224 mg/dL
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
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
Normal
ATT > 5,8 : FH patient
Descamps O. Atherosclerosis 2002.
157: 514-518
Familial Hypercholesterolemia (FH) We don’t have 6me ! •  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 ! Intima
Media
Carotid Ultrasonography
De Groot E et al. Circulation 2004: 109:1133
Familial Hypercholesterolemia (FH) We don’t have 6me ! Le cholestérol se dépose
dans la paroi artérielle
Zone critique
(symptomatique)
Age de la première
complication:
35 ans
ans
Zone silencieuse Non HF
traitée
(asymptomatique)
10
20
30
45 ans
HH traitée
tardivement
40
50
60 ans
HF traité
précocement
60
70
Population
générale
70
Age (années)
Familial Hypercholesterolemia (FH) Treat … to reduce cardiovascular disease (CVD) Comparison of CVD occurrence In treated FH pa<ents Versus untreated FH pa<ents Vermissen et al. BMJ 2008; 337: a2423
Comparison of CVD occurrence In subjects treated from childhood versus their FH parents treated from adulthood. 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 Sta<n Eze<mibe
Ideal LDL-­‐C targets Children (8-­‐10 yrs) Adults . Low dose If necessary
Max potent sta<n dose In most pa<ents <135 mg/dL
<100mg/dL <70mg/dL if CHD/diab Familial Hypercholesterolemia (FH) : Correct as Intensively and as early as possible 732 HeFH patients
(100% statin and 55 % on ezetimibe
134 - 144 mg/dL
148 - 153 mg/dL
New treatment for FH !
Anti PCSK9 Antibodies
1-2 x / Month
- Praluent (SANOFI)
- Repatha (AMGEN)
66 - 76 mg/dL
45% LDL reduction !
80% on target !
Familial Hypercholesterolemia (FH) Not Rare at All !!! •  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) GHHAINAUT PROJECT
(1996) Genetic
GHHAINAUT
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
ê
Suspected
relatives
Data (anonymous)
Funding : Ligue Cardiologique
Belge
GHHAINAUT PROJECT
(1996)
GHHAINAUT
Genetic Hypercholesterolemia in
Hainaut
 RESULTS
 (in 1 year):
Phase 1.
91
(Index patients)
ê
Phase 2.
(Relatives) 26
182
63
54
42
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
KOALA-LOU PROJECT :
CASCADE SCREENING IN FAMILIES OF
FH PATIENTS LIVING IN LA LOUVIERE /
MANAGE
 OBJECTIVE : Identify all relatives with in the family of patients already for FH
diagnosed (by genetic test)
 METHODS. « Flying nurse » + Cascade Screening + Genetic/Clinic
DNA FH
Diagnosis (since
1995)
N = 744
ê
FH Patients
living in La
Louvière or
Manage
N= 88
éê
Cholesterol (& genetic) tests
Funding : Mutualité Chrétienne, Ligue Cardiologique Belge,
PHARMA (MSD, ASTRA ZENECA, AMGEN, SANOFI)
17
KOALA-LOU PROJECT :
 RESULTS
CASCADE SCREENING IN FAMILIES OF
FH PATIENTS LIVING IN LA LOUVIERE /
MANAGE
Index Patients
with FH
in LaLou-Mana
69
88
+
93
643
314
207
49 < 25 years)
= 181
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 !
SITUATION IN
BELGIUM ?
Statin Reimbursement for FH 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
SITUATION IN BELGIUM
PHARMANET DATA (INAMI
2014)
Number of patients by age class
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)
Age
(N=12185)
Categories
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)
Mais Peu sont
v  Maladies Cardio-Vasc
précoces sont évitables si
cholestérol traité avant 20
ans
v  Identifié !
v  Mal génétique doit être
dépistée en famille
v  « Aware »
v  Traité à temps !
v  Recherché dans famille
et l’enfance
è ATTENTION
è CONSCIENTISATI
ON
- BELGIAN FH PATIENTS ASSOCIATION -
Internet website
WWW.BELCHOL.BE
Press conference
Press communication
Parliament conference
Newspaper articles
Conclusion. L’hypercholestérolémie
Familiale … Un paradoxe ?
v  FH est fréquente
(25000 Belges)
Mais Peu sont
v  Mal Cardio-Vasc précoce
sont évitables si cholestérol
traité avant 20 ans
v  Identifié !
v  Mal génétique doit être
dépistée en famille
v  « Aware »
è ATTENTION of
ALL
è ALERT on LAB
protocol
è
v  Traité à temps !
REIMBURSEMENT !
v  Recherché dans famille è THINK FAMILY
et l’enfance
+
General
Practitioners
Pharmacists
Specialists
Government
INAMI/RIZIV
+ MUTUALITY
Total cholestérol = 400 mg/dL ?
Prof. Leiv Ose Paediatrician 24
at University of Oslo Thank You !
First meeting of Belgian FH patients at the Jolimont Hospital
Homozygotes FH • 
• 
• 
• 
• 
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, …).
26