00:00:00
okay I think we should get started um
00:00:03
welcome to everybody my name is Dr Mary
00:00:05
McGowan I'm the chief medical officer of
00:00:07
the family heart foundation and I'd like
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to welcome you to our um Family Heart
00:00:11
Foundation webinar uh titled lipoprotein
00:00:14
little a who is most at risk and uh Dr
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we're very pleased that Dr obha candle
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wall um from Stanford is joining us to
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give us our presentation tonight um hope
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you all experienced LP littlea awareness
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day um this is really LP littlea
00:00:31
Awareness Month um so that's the reason
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for this webinar next slide
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please just a little bit of uh
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information um this webinar is really
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for your information uh the content is
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not intended to be a substitute for
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medical advice diagnosis or treatment
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and it does not constitute medical or
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other professional advice um medical
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information is constantly changing as
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you will hear tonight Dr kandal will be
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describing some new studies around LP
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little a so um this information is um
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for your information this webinar is for
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your information and um some of the
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information may change over time we do
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encourage you to follow up with your
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medical team for your specific
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recommendations pertaining to um the
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treatment of LP littlea or other issues
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that you may have next
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slide we'd like people to say hello
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there's a lot of people on um the
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webinar tonight I'm well over a hundred
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so far are um but you can use the chat
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to introduce yourself and make sure that
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you change the settings to everyone so
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everybody can meet you and just let us
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know what you're hoping to um get out of
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tonight's uh webinar next
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slide if you have a question you want to
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use the Q&A um area of the screen it's
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down below it's to the right of of chat
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and if you ask questions um I will be
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taking those questions down during the
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uh during the webinar and I'll be able
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to direct those questions to Dr kandle
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wall at the end of the webinar so please
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make sure that any questions you may
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have you you put in there next
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slide I want to thank our sponsors um
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sponsors for LP littlea awareness day
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and sponsors for LP littlea community in
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action and now I want to take the
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opportunity to introduce our speaker um
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abhar Kwa is an Imaging C ologist who
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has clinical experience in the
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prevention of cardiovascular disease
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particularly in high-risk populations
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she serves in several capacities at
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Stamford um the ambulatory clinic clinic
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chief for cardiovascular medicine and
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the non-invasive Cardiology section her
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research spans clinical trials in
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preventive Cardiology as well as cardio
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obstetrics Imaging and women's heart
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health she's been involved in phase two
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and phase three clinical trials for
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elevated lipoprotein little a and we're
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very pleased that she serves as a
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scientific on the scientific Advisory
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board for the family Heart Foundation
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welcome abha and we're looking forward
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to your conversation with us today thank
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you Dr McGowan I appreciate the warm
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welcome and very kind introduction um I
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very excited to be here and talk about
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uh lipoprotein little a it has impacted
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me very personally in my family and I'm
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sure several of those who are listening
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today um I'm going to just share my
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screen can we see my screen
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okay yes great so um I just again want
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to thank you all for taking time out of
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your uh day and evening to talk about
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lipoprotein a which is a molecule that
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I've been studying for the better part
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of the last two decades and um like I
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said has impacted several of those
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around me I may use the word lipoprotein
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a LPA LP little a
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interchangeably but um I am talking
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about the same
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molecule and so briefly what I'd like to
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do is talk about the background of
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lipoprotein a and its relationship to
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LDL uh I will talk about the risks
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associated with LP littlea and screening
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and diagnosis who we think is most at
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risk and I will talk about the overview
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of how we manage individuals with this
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condition and I'm very excited to share
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some uh future research that is um on
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the
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horizon so why we're here today we all
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know that heart disease is the number
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one killer of both men and women in this
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country and we're going to talk about
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the biological contributors to this
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today but we cannot ignore that there
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are significant socioeconomic
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contributors and Geographic contributors
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as well when we look at heart disease
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death rates across the US with areas
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that are disproportionately affected in
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darker red across the top we can see
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that there are areas uh where your ZIP
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code matters and unfortunately when we
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overlay poverty areas by county of below
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one can see that they are they map
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pretty closely together we know that
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about one in eight individuals during
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this study period were living in poverty
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and this was higher for African-American
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and Latino women we also know that
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families headed by single mothers were
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almost six times more likely to live in
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poverty so though we are going to spend
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the rest of the time talking about the
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biology I want us to remember that there
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are other significant factors that do
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contribute to heart disease death
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rates so moving on what is lipoprotein
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little a well it's a molecule that was
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first uh identified
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by uh Dr krie Berg a geneticist in the
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1960s and when we look at lipoprotein a
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we can kind of classify these different
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particles based on their density their
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size and their components and so we kind
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of look at it on the spectrum of apob
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particles which you can see here it
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shares some structure with LDL here um
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there is a difference which I'll show
00:06:23
you in the next slide where lpla also
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has an apoa component that's tethered to
00:06:30
the APO by a disulfide bond but so again
00:06:33
when we're looking at different
00:06:34
particles in lipoproteins we can look at
00:06:36
the apoa and the apob it's considered
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part of this um apob spectrum of
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atherogenesis uh and as we know that it
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does we we suspect that some of it
00:06:48
evolved from hedgehogs and bamboom and
00:06:51
we don't truly know its function though
00:06:53
there are some speculations uh and
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theories as to previously it may have
00:06:58
played a role in um
00:07:00
clotting and bleeding issues but again
00:07:03
we don't know its receptor fully and at
00:07:05
this time don't fully understand its
00:07:07
function in in
00:07:10
humans so looking at this structure more
00:07:13
closely uh here we see uh the LDL like
00:07:18
core with APO B attached to the APO a
00:07:22
which you see around the sides you can
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see these little Pringles named after
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their similarity to Danish pastries
00:07:30
and uh what we can note is that again
00:07:33
I'm not going to go into too much detail
00:07:34
but the number of these cringle repeats
00:07:38
can often times determine what your
00:07:40
plasma levels are for the lp little a
00:07:44
also in addition to this apoa component
00:07:47
we also have this oxidized phospho liid
00:07:50
uh component to the structure which
00:07:52
really makes this a pretty um malignant
00:07:55
molecule When comparing it to just LDL
00:07:57
alone and most importantly I want I want
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you to be aware that one in five people
00:08:02
have an elevated LP little
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a and as I was talking about before
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there was a very recent study just
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earlier this year published by Dr bornon
00:08:12
and all that looked at a large
00:08:14
population in the UK biobank and looked
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at individuals with LPA versus LDL and
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looked at incident risk of heart disease
00:08:23
and what they found was that that per
00:08:26
particle the LPA was about six times
00:08:30
more
00:08:31
atherogenic than LDL now I just want to
00:08:35
remind us all that LDL in general for
00:08:38
most of us are much more abundant in our
00:08:41
our bloodstream so they still carry the
00:08:43
greatest proportion of overall
00:08:44
cardiovascular
00:08:45
risk however again per particle it is
00:08:50
considered six times more
00:08:52
aogen and so going back to the structure
00:08:56
uh you know why is this so does it just
00:08:58
cause Arro or there other mechanisms of
00:09:00
its uh action that can influence its
00:09:04
manifestations so first when we talked
00:09:06
about it we talked about the atherogenic
00:09:08
core with the LDL particle at at the
00:09:11
center of the of the figure but we also
00:09:14
note that there is a role in increased
00:09:17
bromus formation or clot formation so we
00:09:21
know that individuals who have elevated
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LPA we can get plaque built up in the
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arteries but we can also have an
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increased risk of clot formation
00:09:30
and then there are some theories as well
00:09:32
to the oxidized phospholipid causing an
00:09:34
inflammatory property that can also
00:09:36
cause other manifestations of the
00:09:39
disease so we focus a lot about heart
00:09:41
disease and coronary artery disease this
00:09:44
is from an editorial I wrote a couple
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years ago and we look at all of the
00:09:49
manifestations of LP little a so we know
00:09:53
that it can manifest as cerebrovascular
00:09:55
disease in the in the way of esic stroke
00:09:58
we already know about the AR coronary
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artery disease but there have been some
00:10:03
um evidence that it may be associated
00:10:05
with atrial fibrillation as well as
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aortic calcific aortic stenosis and then
00:10:11
we also know its role in um Peripheral
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arterial disease which you know is a
00:10:16
plaque build up in the other arterial
00:10:21
beds so we believe that LP Gene kind of
00:10:24
started in the African subcontinent
00:10:26
which may partially be responsible for
00:10:28
the two to threefold increase in um
00:10:32
African-Americans for this condition uh
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it then subsequently migrated Out of
00:10:37
Africa to other areas and what we do
00:10:40
know is that uh the prevalence of
00:10:42
elevated LPA uh greater than 50
00:10:44
milligrams per deciliter or greater than
00:10:47
125 nanomols can affect one in five
00:10:50
individuals and almost 1.4 billion
00:10:53
people worldwide there has been some
00:10:56
data to suggest that the prevalence is
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high high in African-Americans and South
00:11:02
Southeast
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Asians um this is one such example we
00:11:07
were part of a large OB observational
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study at Stanford um called Heritage and
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it enrolled over 48,000 individuals uh
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across over 40 countries and they looked
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at uh this is this is work from Dr
00:11:21
Shapiro's Group which was looking at a
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subgroup of this and the breakdown of
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prevalence of LPA and LDL across various
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ethnicities what he noted was compared
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to the overall group black participants
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and in particular female participants
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had higher median LPA values so one and
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two black participants had an elevated
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LPA uh exceeding 125 nimals and what he
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also noted was that Hispanic
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participants had a slightly lower median
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LPA value compared to the overall
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group so how is LP little a
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inherited so what we do know is it is a
00:12:03
little complicated however if you have
00:12:06
an elevated LP littlea each of your
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first-degree relatives is at increased
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risk of inheriting LP littlea so they
00:12:14
should be considered for
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screening how well are we doing as
00:12:21
health care providers and diagnosing
00:12:23
LPA um I will highlight work by Dr
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mcowan here where she looked at at her
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and her colleagues looked at over 44
00:12:32
million adults through the medical
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claims database and unfortunately what
00:12:38
they found was only about 1% of adults
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know their LPA values and of note uh
00:12:46
those with ascvd it's it's not much
00:12:48
better so I think there's definitely
00:12:51
work to be done and in addition when
00:12:53
looking over time we saw a great
00:12:56
increase in
00:12:57
2019 um of individuals getting screened
00:13:02
however we see this lull in 2020 and
00:13:05
2021 and you know we speculate that
00:13:09
potentially co could be partially
00:13:11
responsible for this uh small decline
00:13:16
here and another thing to note is that
00:13:20
anyone can be affected it doesn't matter
00:13:22
how fit you are in fact I don't know if
00:13:25
many of you watch the biggest loser but
00:13:27
Bob Harper is a celebrity fitness
00:13:29
trainer from that show and he suffered a
00:13:31
heart attack and it was eventually um
00:13:35
noted that it was partly responsible by
00:13:38
because he had um lipoprotein little
00:13:42
a so it again it doesn't differentiate
00:13:46
whether you're fit or not um so when we
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look to our medical societies on who we
00:13:52
should screen who you know how we should
00:13:55
test for this uh there are different uh
00:13:58
guidelines and different
00:13:59
societies uh my personal view is that
00:14:02
it's a very lowrisk test and oftentimes
00:14:07
low cost and I think all adults should
00:14:10
be screened but when we look at the
00:14:12
European Society of um the European
00:14:15
Society guidelines they also think that
00:14:17
all adults should be screened um same
00:14:20
with the Canadian guidelines our us
00:14:22
guidelines from the American College of
00:14:24
Cardiology and aha at least in the last
00:14:27
um iteration of their guidelines did not
00:14:30
give specific um screening
00:14:34
recommendations but my hope is that in
00:14:37
future guidelines and I I think that my
00:14:40
colleagues share this view that
00:14:41
hopefully in future guidelines they will
00:14:43
address this a little bit more clearly
00:14:45
and hopefully um support some of these
00:14:48
other guidelin
00:14:51
statements um and just to note
00:14:53
individuals who have very very high LPA
00:14:56
may actually have an increased risk of
00:14:59
uh cardiovascular disease similar to
00:15:02
those with familial hyper lipidemia or
00:15:05
FH which is another condition that you
00:15:08
all may be familiar
00:15:15
with so you know one of the arguments I
00:15:18
get from some of my patients is well why
00:15:22
why do you think it's appropriate to
00:15:23
measure LP delay in everyone and to me
00:15:27
it's an it's a risk factor it's an
00:15:29
independent risk factor associated with
00:15:32
an increased risk of heart disease
00:15:33
stroke and aeroic stenosis so I think
00:15:36
it's important to know um I think it's
00:15:38
very common so I think that's an it's
00:15:42
very easy to pick someone up uh it's
00:15:45
something that you don't have to do over
00:15:46
and over again it's a genetically
00:15:48
determined predominantly so it remains
00:15:52
relatively constant um throughout one's
00:15:55
Lifetime and I do think that it is
00:15:58
compliment entry with regards to other
00:16:01
lipid testing so it can kind of
00:16:03
additionally R stratify individuals
00:16:05
beyond their traditional lipid panel um
00:16:08
to me I see a lot of high-risk uh
00:16:11
younger women I think the potential for
00:16:14
early intervention is huge if you can
00:16:16
identify these individuals early you can
00:16:18
work on their other risk factors and
00:16:20
potentially prevent future disease I
00:16:23
think at least initially we should try
00:16:27
for Cascade screening so if we do
00:16:29
identify someone with elevated LP
00:16:32
getting all their first-degree relatives
00:16:33
screened would be important and I think
00:16:36
in the next couple years we may see
00:16:38
increasing therapeutic options available
00:16:41
so in order to effectively utilize these
00:16:44
options we need to identify those who
00:16:46
will be most benefited um I think that
00:16:50
Universal
00:16:51
screening it it kind of is more
00:16:53
appropriate when you look at it through
00:16:55
an equity lens so you can detect disease
00:16:58
regardless of a person's zip code so I
00:17:00
think that's also an important thing to
00:17:02
think about and I think by screening
00:17:04
you're engaging our patients and
00:17:06
increasing their awareness and making
00:17:09
them really Partners in their health
00:17:10
care so I think that's very important
00:17:12
and if we look at all the other
00:17:13
screening measures that we do I do think
00:17:15
it's a very cost-effective long run
00:17:20
intervention and just again to highlight
00:17:22
Dr McGowan's work unfortunately less
00:17:24
than 1% of the population has actually
00:17:26
been tested at any when in their life
00:17:29
and so we as Healthcare Providers have a
00:17:31
lot of work to do
00:17:34
here when looking at LPA values one may
00:17:38
ask what is a normal lipoprotein a and
00:17:40
what's elevated we consider it elevated
00:17:43
when it's greater than 50 mg per
00:17:46
deciliter or greater than 125 nanomoles
00:17:50
per
00:17:53
liter how may your healthcare provider
00:17:56
document that you have an elevated LP
00:17:58
little a
00:18:00
well luckily in
00:18:02
2018 we had icd10 codes that were
00:18:05
approved and maybe added to your medical
00:18:07
record for elevated lipoprotein a or
00:18:10
family history of elevated lipoprotein
00:18:15
a and I alluded to this before but is
00:18:18
this a test that we need to do every
00:18:20
year every six months no I I don't think
00:18:23
so um I think it is fairly stable over
00:18:28
an IND indidual life in over an
00:18:30
individual's Lifetime with some minor
00:18:33
exceptions so we generally reach our
00:18:35
adult level of LPA by around the age of
00:18:39
five uh there are some exceptions for
00:18:42
later in life where the values may
00:18:44
change so menopause may change the
00:18:48
values for LPA and sometimes
00:18:50
substantially we know that estrogen can
00:18:53
lower LPA and in menopause estrogen does
00:18:57
decline significantly so we may see as
00:18:59
much as a 20% increase in LPA around
00:19:03
that time we're also aware of LPA as an
00:19:06
acute phase reactant this means that it
00:19:08
can actually increase when there is a
00:19:11
major uh physical stress or illness
00:19:15
infection an acute heart attack or major
00:19:18
surgery um but what we do know also from
00:19:22
one of the uh novaris uh pelic Carson
00:19:25
studies one of the newer treatment
00:19:26
option studies that that there are some
00:19:30
natural biological variations and in
00:19:32
some individuals it may be as much as
00:19:34
about
00:19:38
20% how do we manage these individuals
00:19:41
with elevated
00:19:43
LPA well you know when we look at the
00:19:45
Epic Norfolk study of about 14,000
00:19:49
individuals what we found is that
00:19:52
individuals with high LPA but few
00:19:55
cardiovascular risk factors were 66%
00:19:58
lower risk for cardiovascular disease
00:20:01
than those with multiple cardiovascular
00:20:04
risk factors so um what we tend to do is
00:20:09
we and I'll go over this a little bit
00:20:11
more in another slide is we really focus
00:20:13
on looking at the cardiovascular risk
00:20:15
factors that are under our control in
00:20:17
these individuals for our current state
00:20:20
management and so when we look at
00:20:22
treatments I I saw some texts in the
00:20:25
chat earlier asking what are the
00:20:26
treatments for this um you know I'm
00:20:29
going to start off with an old but good
00:20:32
medicine known as aspirin a baby aspirin
00:20:35
and this again is hot off the press Dr
00:20:37
sas's group just earlier this year um
00:20:40
looked at the Mesa data set which is a
00:20:44
large group of individuals um that
00:20:47
previously did not have heart disease
00:20:50
and looks at aspirin users and
00:20:52
non-aspirin users and what he found in
00:20:56
this graphic you can see so in the two
00:20:58
shades of red are those individuals with
00:21:01
elevated lipoprotein over time and what
00:21:04
we see is in the darker red those
00:21:06
without aspirin use have future
00:21:10
cardiovascular event rates but the ones
00:21:13
in the bright red are a little bit
00:21:15
closer to those uh that have lower lpal
00:21:19
aays whether they used aspirin or not so
00:21:22
overall he noted a 46% reduction in
00:21:25
cardiac events in those individuals with
00:21:28
elevated lipoprotein a who took a lowd
00:21:31
do aspirin compared to those who did not
00:21:34
now as a healthare practitioner and as a
00:21:37
physician all of these things have to be
00:21:39
individualized and discussed on a per
00:21:42
patient um basis because we also have to
00:21:45
look at the risk of
00:21:47
bleeding so as I said before there are
00:21:51
other things that we can look at as well
00:21:53
including your other
00:21:55
cardiovascular risk factors so though
00:21:58
diet and exercise may not immensely
00:22:02
impact the value of your lipoprotein a
00:22:05
they are actually very important in
00:22:07
managing patients with this condition we
00:22:10
recommend a very aggressive diet um and
00:22:13
lifestyle plan for our individuals with
00:22:15
elevated lipoprotein a we will ask them
00:22:18
to reduce their saturated fat we'll ask
00:22:21
them to take a high soluble fiber diet
00:22:24
and when they're unclear if there are
00:22:26
ethnic specific dietary concern concerns
00:22:28
we will'll refer them to a dietitian uh
00:22:31
who can work with them on a proper meal
00:22:33
plan and we do recommend regular uh
00:22:36
symptom limited exercise and then we
00:22:40
work individually on the the patient or
00:22:42
on the individual based on what their
00:22:44
other cardiovascular risk factors are so
00:22:46
if they have high blood pressure if they
00:22:48
have diabetes metabolic syndrome if
00:22:50
they're overweight or obese if they're
00:22:53
smoking or not active and we will
00:22:55
aggressively
00:22:56
intervene upon each of these uh risk
00:22:59
factors based on what the individual
00:23:02
needs and you know one of the
00:23:03
cornerstones to treating uh patients
00:23:06
with this condition is also treating
00:23:08
their LDL and we have now a huge
00:23:12
armamentarium of treatment options for
00:23:14
individuals to get their LDL to to lower
00:23:18
targets we know that diet can lower LDL
00:23:21
by 10 to 15% we have statins we have
00:23:24
medicines like bile acid sequestrant we
00:23:26
have some newer agents called pcsk9
00:23:30
Inhibitors that really can reduce the
00:23:33
LDL by a very significant value and then
00:23:36
we also have agents like bidic acid and
00:23:40
zidia um that can also reduce LDL
00:23:43
anywhere from 15 to 30 to
00:23:45
40% so we have a lot of good options in
00:23:49
uh treating
00:23:51
LDL and in fact some of these LDL
00:23:55
therapies can influence LPA as well so
00:23:59
you know as of now diet there's no
00:24:02
significant impact on LPA there may have
00:24:05
been prior data looking at saturated fat
00:24:08
May lower it slightly but this is not
00:24:10
recommended uh nasin can lower LPA by
00:24:14
20% but I'll talk about that more in
00:24:16
another slide statens can raise LPA by
00:24:20
up to 10 to 15% but again um when
00:24:24
looking at the individual our goal is to
00:24:27
lower their overall risk and LDL is
00:24:30
still a critical component of that and
00:24:33
so it becomes you know a discussion and
00:24:35
we do not withhold stattin for this
00:24:38
small rise in LPA uh and then we don't
00:24:41
we're not aware of any significant
00:24:43
effect with bmid doic acid or zidia on
00:24:45
LPA we know that pcsk9 Inhibitors can
00:24:48
reduce it anywhere from 15 to
00:24:50
30% and estrogen lumpi can also lower it
00:24:54
slightly the only FDA approved treatment
00:24:57
for LPA reduction is lipoprotein
00:24:59
apheresis and I will go more into um
00:25:03
that in a future slide but it can reduce
00:25:04
your LPA values by almost up to
00:25:09
35% and it's um FDA approved in
00:25:13
individuals who um meet very specific
00:25:18
criteria so when we talk about estrogen
00:25:21
um we had a similar kind
00:25:24
of discussion about this when we were
00:25:27
looking at LDL treatment
00:25:28
but what we do know is that estrogen
00:25:31
lowers LPA but data from the women's
00:25:34
health initiative and um some other
00:25:36
studies found that hormone replacement
00:25:38
therapy itself has increased Adverse
00:25:40
Events like breast cancer blood clots
00:25:43
and stroke so it is not routinely me um
00:25:46
estrogen is not routinely recommended to
00:25:47
lower LP L and again the Val the
00:25:50
reduction is pretty um marginal
00:25:54
comparative to some of the newer options
00:25:56
I'm going to tell you about in in a
00:25:57
brief moment
00:25:58
nasin can also lower LP littlea but
00:26:02
again there was not a benefit found in
00:26:04
patients who were already on a Statin in
00:26:06
other studies uh also just I will speak
00:26:09
from my perspective and I think each
00:26:11
physician has their own view on this is
00:26:14
that nce and comes with a lot of side
00:26:16
effects and so I don't routinely use it
00:26:19
um because it can increase blood glucose
00:26:22
there's GI bleeding and risk of gout so
00:26:24
it really has to be an individualized
00:26:26
risk benefit discussion with your doctor
00:26:31
um I spoke to you about pcsk9 Inhibitors
00:26:34
and we know that they can lower LPA by
00:26:36
anywhere from 15 to 30% and two of our
00:26:38
major outcome studies for these agents
00:26:42
called fora and odyssey outcomes both uh
00:26:46
demonstrated that LPA reduction may have
00:26:49
contributed to the ability of these
00:26:51
agents to reduce cardiovascular events
00:26:54
um but as of right now pcsk9 Inhibitors
00:26:57
are not FDA approved for LPA
00:27:01
reduction and then as I mentioned before
00:27:04
lipoprotein apheresis it not only lowers
00:27:06
LPA but it actually lowers LDL as well
00:27:09
it is a commitment and it takes time and
00:27:12
is costly but it can be um an option for
00:27:16
individuals with established
00:27:17
cardiovascular disease and persistently
00:27:19
elevated values
00:27:21
um and and for the treatment of LPA as I
00:27:26
said so this is the part that I'm very
00:27:28
excited to share with you there are a
00:27:30
lot of new therapies and development for
00:27:32
lpla and um I'm going to just briefly
00:27:36
talk about the general mechanism of
00:27:38
action of these new class of Agents they
00:27:42
all have their subtle differences but uh
00:27:44
this product is the one that I was most
00:27:46
familiar with as we were part of like
00:27:48
the phase two studies for This was um
00:27:50
the you know they all work on your
00:27:54
genetic
00:27:55
transcription and so like you have your
00:27:57
DNA that's kind of your blueprint and
00:28:00
then it translates to mRNA which then
00:28:02
kind of manifests and builds the the
00:28:05
offending protein so what you can see
00:28:07
here is a lot of these agents that are
00:28:09
being developed are called anti-sense
00:28:12
Alon nucleotides and they work right
00:28:15
here from the MRNA to the protein
00:28:17
transcription so they're very very
00:28:18
specific they're very very targeted and
00:28:21
they're very effective so all these
00:28:23
other agents I was telling you are
00:28:24
reducing LPA by 15 20 maybe
00:28:28
30% uh in in our studies with ionis we
00:28:32
saw the reduction in LPA almost 80% so
00:28:36
very
00:28:37
impactful in terms of its ability to
00:28:39
reduce lipoprotein
00:28:42
a so again as I was alluding to this is
00:28:45
probably the most mature agent that's
00:28:47
being studied uh it's from novaris pel
00:28:50
Carson is the name it's an anti- sensil
00:28:53
nucleotide and can lower LPA by
00:28:56
80% and we've already closed enrollment
00:28:59
for the Horizon trial which is a phase
00:29:02
three outcomes trial uh it's a secondary
00:29:05
prevention study looking at subcutaneous
00:29:07
injections um versus placebo per month
00:29:11
and it will continue for about four
00:29:12
years or until we have about 993 events
00:29:16
and likely be completed in the next year
00:29:18
or
00:29:21
two after this we have amen's particle
00:29:24
it's also a small interfering RNA called
00:29:26
Al pasaran they are near trial um
00:29:31
completion for enrollment I believe and
00:29:34
you know they have about 7,000
00:29:36
individuals enrolled again this is a
00:29:38
secondary prevention study looking at
00:29:41
individuals with LPA with uh value
00:29:45
greater than 200 nanomoles per deciliter
00:29:48
and uh they have to have had evidence of
00:29:50
atherosclerotic cardiovascular disease
00:29:53
and it's a subcutaneous injection every
00:29:55
3 months and their preliminary Phase 2
00:29:58
data says it may lower LPA by up to
00:30:02
95% um another product that is um
00:30:06
starting enrollment is leodan by Lily
00:30:09
again another small interfering RNA um a
00:30:12
claim is a randomized double blind
00:30:16
controlled Placebo control trial to look
00:30:18
at this agent um in individuals with
00:30:21
established
00:30:23
ascvd and those at high risk so this is
00:30:27
one of the few studies as looking both
00:30:28
at secondary and primary prevention in
00:30:32
um high-risk individuals and it's going
00:30:35
to attempt to enroll about
00:30:38
12,500
00:30:39
individuals uh with an significantly
00:30:42
elevated LPA
00:30:44
value I'm going to continue briefly on
00:30:47
some of these other agents there's
00:30:48
another small interfering RNA from
00:30:50
Silence Therapeutics called zel zerin
00:30:53
again it's in a phase two um looking at
00:30:56
LPA greater than 120 and and I believe
00:30:58
this is also a secondary prevention um
00:31:02
trial and mapin uh actually had some of
00:31:05
its Origins at Stanford uh is another
00:31:08
product by Lily that's being studied
00:31:09
looking at apoa and B um bonding and
00:31:14
looking at the heasy level um but hasn't
00:31:17
yet entered U phase two
00:31:20
trials and then there is actually
00:31:22
another uh therapy for LDL reduction um
00:31:25
which is kind of a CP inhibitor so so
00:31:28
when we have these cholesterol particles
00:31:31
floating around in our bloodstream they
00:31:32
often um components of it are
00:31:34
transferred to different particles
00:31:36
making them you know LDL HDL um vldl
00:31:40
these various cholesterols so OB
00:31:43
citb is one of those that inhibits kind
00:31:46
of this transferring of some of
00:31:48
the the particles and it's current
00:31:52
dosing strategy is about 10 milligrams
00:31:53
per day and it can reduce LDL by almost
00:31:56
50% but also lowers LPA by about um 56%
00:32:02
and so they are conducting a 9,000
00:32:04
patient cardiovascular outcomes trial
00:32:07
with individuals with underlying
00:32:09
vascular disease that started a couple
00:32:10
years ago and it's hoping to complete in
00:32:12
the next couple years done by New
00:32:14
Amsterdam
00:32:17
Pharma so with that I hope I've been
00:32:20
able to give you um a brief overview
00:32:23
about LP a and its relationship to LDL
00:32:27
I've spoken brief about the risks
00:32:28
associated with LPA and its various
00:32:31
manifestations and not just
00:32:33
cardiovascular heart disease um we've
00:32:36
talked about who should be screened my
00:32:38
opinion everyone but um potentially
00:32:41
those at high risk and uh we've talked
00:32:44
about once patients are diagnosed how we
00:32:47
can manage them and I've also briefly
00:32:50
spoken about areas for future research
00:32:52
and opportunities um for participation
00:32:55
in clinical trials so
00:32:59
um with that I just again want to remind
00:33:03
everyone why I'm here which is to help
00:33:06
raise awareness um I hope you'll help me
00:33:09
do that by kind of making a mental note
00:33:12
of an action item that you hope to to do
00:33:14
after this webinar today I know that um
00:33:18
you've take given me your time this
00:33:20
evening which is a good first step but I
00:33:22
hope that you'll continue this
00:33:23
conversation with your loved ones and if
00:33:26
um they not aware of this condition
00:33:29
informing them about it and ideally
00:33:31
having them um discuss whether they're
00:33:34
they should be screened with their care
00:33:36
provider so I wanted to leave plenty of
00:33:39
time for questions
