We're doing a series on cardiogenetics this one's on familial hypercholesterolemia
now there's been a debate for a long time if you ask over 90% of doctors they'll say
the majority of cardiovascular risk has to do with cholesterol there's the other side
of that argument there are others that say no actually cholesterol is not a problem at all
and in fact you listen to some people and they say you want to have high
LDL values now what's the story here I'll tell you I don't fall in either of those camps completely
we'll talk about a little bit more where I fall and what and some of the reasoning
behind that we've done several videos on FH we've talked about a couple of stories Sue
who had challenges and then has gotten beyond them Jake the same thing we've talked about signs and
symptoms and why it might be a problem waiting for a sign or symptom we've talked about drugs
and the lifestyle issues associated with managing this problem now wait a minute is this a mistake
I'm starting off on a deck on FH familial hypercholesterolemia and then I go into 9p21
those of you who remember it may remember that 9p21 the 9th chromosome the p21 area that's
the heart attack gene some of you may have read Brad Bale and Amy Doneen's book Beat the Heart Attack
Gene what's that doing in an FH deck I'll get to that a little bit later but let's go back and talk
about this theme that you continue to hear from me Sue is a great example of this theme that it's not
just FH alone it's FH plus something else as a young woman in her mid-30s she went hiking
came home had some chest pain went to her doctor and the doctor said you know what I think this
is just the nervousness that I often see in young women not really significant chest pain
didn't draw blood didn't really look any deeper sent her home she went back within a day or two
and said I think you need to draw some blood check on some things this is more than just nervousness
sure enough she had FH and she ended up having a five vessel bypass over the next couple of days
she was fine then but let me go back and say well was that her FH it was more than just her FH
obviously her doctor began to listen to her more when she said this is not just nervousness but
she also began to listen to her doctor when he said Sue you got to quit smoking so it was FH
and smoking she did find from that point up until about her mid-50s when she needed to have
another bypass and here was the problem at that point she'd gotten nervous about this
FH problem she like many of us do dealt with her nervousness by eating too much she had gotten
obese she needed to lose a lot of weight and she did she lost 125 pounds her brother actually calls
her half a Sue now because she lost about half her body weight at this point she's over 70 years old
she's not taking statins that's her choice but she's healthy right now and the point is this FH
doesn't always cause events often it doesn't cause events at all on its own but it's FH plus smoking
plus obesity plus insulin resistance and plus some other things that we'll talk about a little
bit later now I mentioned we covered Jake's story we've got a whole series on Jake's story he's 40
year old known lean mass hyper responder now that term was coined by a fellow named Dave Feldman
and I agree with a lot of what dave Feldman describes in regards to lean mass hyper-responders
there's a couple of places that we don't 100% agree for example one of them is a statement by
Feldman that lean mass hyper-responders are not FH patients i would say sometimes that's correct
but if you begin to realize how big the universe is of people with different versions of FH
you begin to go back and really doubt that statement we'll talk about just how big that
universe is in just a minute how many people and how many variations you can have of FH back
to Jake's story he clearly had a family history he managed his to a large extent with lifestyle
there was a time when he needed medications but again he's a great example of the importance of
lifestyle in managing this problem now I can't talk about FH and not talk about this issue you
look it up in a book and they'll say well what are the signs of familial hypercholesterolemia
they'll mention xanthelasma you don't need to know that term you just look at these and
you see these little white specks in the Achilles' heel in the eyelid and the eye itself in knuckles
those are actually deposits of cholesterol don't wait for those that's the problem waiting to find
people with signs of disease is as bad as waiting for people to show signs of insulin
resistance prediabetes atrial fib cardiovascular inflammation don't wait for signs don't wait for
symptoms you don't have those tests don't guess go ahead and have a degree of suspicion and start
checking people out getting yourself checked out so a couple of words about the genetics
of familial hypercholesterolemia just real quick this is from the FH Foundation website and they
give you a good description with an image showing what heterozygous versus homozygous is
that's helpful until you get to the next slide and we'll talk about that next slide when we get there
heterozygous means you've inherited one from your mom or dad but not from the other and homozygous
means you've inherited one from both of them I'll give you a brief comment about a couple of slides
down there are over 1,200 different variations so what if you inherit one category from your mom
in another category from your dad or three or four from each that's when it becomes complicated
and a much bigger deal and now you're beginning to get back to what I was talking about when I said
the universe of FH is far bigger than most doctors realize the FH Foundation site does great graphics
they've got a great graphic here showing that 90% of people with this problem are undiagnosed
and again as you go back to my example on just how many types of variations there are the
failure of the medical community to have an index of suspicion to screen for this then you begin to
realize that 90% is probably a very low estimate of the number of people that have this problem
but just are not being tested can't have any discussion about FH with talking just briefly
about medications people always ask about it yes the vast majority of my folks focus on lifestyle
but beyond lifestyle are their medications yes the vast majority of my patients do well
on statins there are other medications Zetia ezetimibe these are medications which decrease
absorption there's an antisense drug it's called mipomersen it's been around for a while
it's dangerous you don't go on mipomersen unless you go on to a special risk management program one
of the reasons mipomersen is interesting is that it's an antisense drug those of you with
Lp(a) another genetic problem may remember that there's a lot of interest right now and great
reviews coming up with antisense drugs for Lp(a) now don't make the connection that if
there are liver problems significant danger with mipomersen for FH then maybe the other antisense
drugs have that same problem I don't think you should be saying that or worrying about that at
that point we'll cover those drugs when we get to Lp(a) the big drug class that's a new
class the PCSK9 inhibitors are the ones that were developed specifically for FH and they've done a
great job but as I've said you're beginning to hear this theme most FH patients really don't
need these level of drugs to do very well to go back I talked for a couple of times about the
large universe of FH there are over 1,200 snips what's a snip wait a minute don't need to know
that it's single nucleotide polymorphism but you don't need to know that term most people think of
this as a mutation here's why you don't hear the term mutation used a mutation only happens once
once it becomes inherited it's a snip a single nucleotide polymorphism I just tend to use the
term genetic variation so here's the thing there are at least 1,200 closer to 2,000 variations
that can result in hypercholesterolemia there are even five classes of them some of them involve
the protein itself remember ApoA forms the HDL particle and ApoB forms the LDL particle
so that's one of the areas to look at another area is the LDL receptor itself you see the liver
waits for LDL to pass through it has receptors when an LDL particle touches a liver receptor
it pulls that LDL into the cell and burns it up it metabolizes it so there are problems with that
receptor there are also problems with the receptor cycling for LDL so I'm getting a little bit geeky
a little bit too deep a little bit too detailed but now maybe you can start to see why there are
so many different variations of genetic problems which can result in familial hypercholesterolemia
one last comment that I make before I finish up is index of suspicion if you've ever had an LDL
180 or above you've got a pretty good chance of having one of these genetic variations
get it checked out now the last thing gets back to the very beginning again am i talking about the
heart attack gene here or FH I'm talking about FH and here's the thing here's what you see on
this slide it's one thing to have the heart attack gene it's a very different thing to have FH but it
appears to be a multiplied risk if you have both so it gets back to that general theme that we've
been discussing over and over again it's not just one genetic risk factor it's the interplay
between multiple risk factors some genetic some lifestyle thank you very much for your interest
continue to get great feedback regarding the webinars and here's why you know on the
internet when you hear a webinar you expect for somebody to try to sell you something we're not
doing that we're trying to tell you something people are coming in with their labs from Quest
inflammation panel OGTT insulin survey response and then they're finding out do
I have inflammation do I have insulin resistance and where does that fit in terms of other folks
we're getting ready to start one for CIMT as well so again people are really
excited about finding out their own status looking forward to seeing you there thanks