Familial Hypercholesterolemia: Defining, Screening, Treating

welcome I'm dr. Sharon Hayes a

cardiologist at Mayo Clinic in Rochester

Minnesota I'm here today with a

colleague dr. regis Fernandez who is a

cardiologist in our Mayo Clinic Health

System to talk about familial

hypercholesterolemia welcome thank you

so why should we have a focus on

familial hypercholesterolemia so

familial hypercholesterolemia or f''f

age is an inherited disorder that causes

very high levels of LDL cholesterol it's

largely under treated and under

diagnosed the patients that have the

phenotype for FH have a 20-fold risk of

having premature coronary disease which

would cause could cause heart attacks in

man aged 50 or even in the 40s and women

younger than 50 about 20% only of

patients with familial

hypercholesterolemia worldwide are

currently diagnosed so you say this is a

familial condition what are the genetics

of familial hypercholesterolemia so

understanding the genetics of FH is very

important in order to understand the

screening FH can happen in two forms a

heterozygous form which is the most

common one which has an autosomal

dominant pattern or trait so one

defective gene from one parent can be

passed to the to the children so 50% of

the children can be affected it has a

children have a 50% chance of acquired

disorder by getting a defective gene

from one parent and that's all it takes

for FH 2 to develop in in the child so

what's the relative prevalence of the

heterozygous and homozygous and what's

different about the homozygous patients

so now heterozygous form the prevalence

about one in five hundred births that

accounts for about 600,000 cases in the

US and over ten million worldwide in the

homozygous form it's a much more rare

form and affects one in 1 million births

and what it's interesting about the

homozygous form is that the child would

get one abnormal gene from each parent


you have very little or no LDL receptor

activity so the child's cholesterol

levels will be very high in the 600 800

range causing premature CA D during

childhood and those individuals need to

be identified and treated very

aggressively very early life in order to

prevent premature see at that age group

so so if how are we you say it's

under-diagnosed how do we screen for

this condition correct so in order to

screen for FH there is general screening

which can be done in the adult

population so through Universal

screening screening one once one

individual is diagnosed with FH then you

can identify other family members

first-degree relatives wrong from that

individual and that's them through

something that is called cascade

screening so cascade screen is also

identify one individual and you screen

the family members a new individual will

be identified and that individual will

give you more family members for you to

continue that cascade so cascade screen

is very cost effective and it's a it's a

very good way to identify patients with

FH it sounds like screening is important

this cascade what some of this is going

to come in children of what are the

recommendations for screening children

correct so if a child has if the the

parents have a history of high

cholesterol or a history of premature CA

D the child should be screened now there

are there's some advocacy advocacy for

screening Universal screening in

children aged 9 to 11 before puberty

where you can detect them out cases of F

age if we if we do that okay so what are

the diagnostic criteria for familial

hypercholesterolemia so in the adult

population if the LDL is greater than

one 91902 would be suspicious for having

FH in the in children and adolescence

the level of 160 is considered the

cutoff okay and then you identify these

individuals how do you treat them

okay the treatment for FH involves more

likely we need to involve a hypothesis

in statin

so after lifestyle modification risk

factor modification diet and exercise

pharmacological therapy will be

necessary for most individuals with the

hypothesis hypothesis statin

so our traditional risk assessments like

Framingham useful in this patient

population no actually it's not

recommended because this population

would FH they have a high short term and

long term risk of premature CA D so the

10-year risk models do not adequately

identify this population or risk

stratified this population actually

known even non-imaging at risk of

erratic imaging is not recommending this

population because most patients will

need to be treated and fine and the

negative findings of atherosclerosis in

an imaging study does not should not

prevent patients to be treated we should

treat them regardless that's what you're

saying yes that's right be aggressive

so what do you see in the future for

these patients and for us is caring for

them well I think first and foremost the

most important thing is to improve

detection and treatment of FH like I

said at the beginning is largely under

treated and under diagnosed so that'll

be the first thing to do and that can be

done through education of the added

level of the community level and also a

healthcare provider level which is what

we're doing here today

and so what do you see in terms of a

future in the future in terms of novel

treatment or or screening so on another


molecular biology has come in

introducing new novel therapies for FH

and in this March issue of New England

Journal and general medicine there was a

study that was published where the

researchers used monoclonal antibodies

to block an enzyme that is a down

regulator of the LDL receptor that cause

the levels of LDL receptor to increase

and reduce LDL levels up to 65% which is

more than what we see with hypothesis

statins without the added side effects

so in the future molecular biology of

the LDL receptor will help to come up

with novel therapies to treat FH for

patients that either don't respond to a

phage or for patients that are

intolerant to statins

thank you I've learned a lot and thank

you for joining us today