Please wait while the transcript is being prepared...
0:00
My name is Steve Humphries.
I'm the British Heart
Foundation Emeritus
Professor of Cardiovascular
Genetics at UCL
and I'm going to tell you about
an inherited disease which
increases the risk of
heart disease, it's
called familial
hypercholesterolemia and I'll be
calling it 'FH' for short
throughout the talk.
0:23
I've divided the talk into
three sections as
you can see here.
0:29
I wanted to start
off by acknowledging
a number of colleagues
who've worked with me at UCL
and at the Great Ormond Street
(GOSH) diagnostic labs,
and in the Simon
Broome Study Group
over the last many years.
0:42
I'm going to start by
showing you a family that
I was approached more
than 25 years ago now.
You can see that
the man here had
a heart attack at the age of
35 years which is
obviously very young.
His untreated total
cholesterol was
8.1 which I'm sure you
appreciate is very high.
His wife had cholesterol levels
within the normal
range and they were
concerned about
their two boys at
the time they were seven
and five years old,
because their cholesterol levels
were a bit on the high side.
The question that
we want to know is:
Does dad have FH?
Can we find the genetic cause
and can we use this
information to see
if either son has FH?
1:20
These are the diagnostic
criteria that we use in
the UK to tell if
someone has FH or not.
There were developed based on
these Simon Broome FH register,
and an individual has to have
total cholesterol
over 7.5 mmol/l,
specifically it's
the LDL about 4.9
mmol/l in an adult,
the diagnostic threshold for
children is slightly lower.
Then, they have to have
a family history of
either high cholesterol
or first-degree
relatives, such as a
male relative who's
had a heart under
the age of 55 years.
If you meet those
criteria, you are given
the clinical diagnosis of
possible FH or if you have
tendon xanthoma or an
FH-causing mutation, you're
given the harder clinical
diagnosis of definite FH.
The high cholesterol which
has been present since birth
tends to come out in some of
the cold regions at the body.
In the eye corneal arcus,
a little patches in
the skin sometimes in
the eye socket
called xanthelasmas,
and then most particularly
in tendons either
in the Achilles, the back of
the heel or in the knuckles.
These are what we call
the Stigmata of FH
as well as this some
improvement criteria,
there's also an American
system called MEDPED
and the Dutch Lipid Clinic
Criteria scoring system.
I'll just mention this in
a bit more detail because
it works in a points method.
What you can see here
is that for each of
the characteristics of FH
you get a certain
number of points.
If you have >8 points
you have definite FH,
between 6-8 it's probable FH
and 3-5 it's possible FH,
and if it's <3 you
don't have FH at all.
You can see from this that if
your LDL cholesterol
is extremely high or
if you have a mutation
in one of the FH
causing genes you
have definite FH.
The worst group have adapted
this by giving negative
points if you have
high triglycerides
since we know that
high triglycerides is not a
feature of the FH phenotype.
