Sep 5, 2016
Carolyn:
Welcome to Circulation On The Run, your weekly podcast, summary and
backstage pass to the journal and its editors. I'm Dr. Carolyn Nam,
associate editor from the national heart center and Duke National
University of Singapore.
In just a while, we will be discussing patients with familial
hypercholesterolemia after acute coronary syndrome, and the new
data in this week's issue that suggests we still need to pay
special attention to this group of patients even in the current era
of the widespread use of high intensity satins. First here's your
summary of this weeks issue.
The first paper suggests that we may need to look at thyroid
function in our risk assessment sudden cardiac death in the general
population. This paper is from co primary authors Dr. Chacker in
Van Der Burgh and corresponding author Dr. Strecker and colleagues
from the Erasmus University medical center in water dom.
The authors studied the association of thyroid function with sudden
cardiac death in more than 10,000 participants of the population
based Water Dom study. They found the higher levels of 3T4 were
associated with an increased risk of sudden cardiac death even in
the normal range of thyroid function. The estimated hazard ratio
was 2.28 per one nano-gram per deciliter of 3T4, and these risk
estimates did not change substantially even after stratification by
age or sex or sensitivity analysis excluding participants with an
abnormal 3T4. The absolute 10 year risk of sudden cardiac death
increased in youth thyroid participants from 1 to 4% within
increasing 3T4 levels.
Thus this study suggests that 3T4 and additive marker in risk
stratifications for sudden cardiac death in the general population.
Further research is needed to assess the possible additional
benefit of using 3T4 levels to re stratify and prevent sudden
cardiac death.
The next study reminds us that therapies to reduce ischemic events
in patients undergoing percutaneous coronary intervention are still
really important even in the current era of changing definitions of
periprocedural myocardial infarction. This study is from first
author Dr. Cavender of University of North Carolina chapel hill and
corresponding author Dr. Bach Brigham women's hospital and
colleagues.
The authors looked at more than 11,000 patients randomized to
cangrelor or clopidogrel int the champion phoenix trial.
Cangrelor is an intravenous P2Y-12 inhibitor approved to reduce
periprocedural ischemic events in patients undergoing percutaneous
coronary intervention who are not pretreated with with a P2Y-12
inhibitor.
The authors explored the effects of cangrelor on myocardial
infarction using different definitions of myocardial infarction and
perform sensitivity analysis on primary endpoint.
They found that 4.2 percent of patients had a myocardial infarction
defined by the second universal definition within 48 hours after
undergoing PCI. When the sky definition of periprocedural MI was
used, there were fewer total myocardial infarction, but the effects
of cangrelor remain significant.
Finally similar effects were seen when MI's were restricted to
those defined with large bio marker elevations or by symptoms of
ECG changes. Very importantly patients who had an MI regardless of
the definition, were at increased risk of death at 30 days.
In summary changes in the definition of MI used in the primary
endpoint did not affect the overall findings from the champion
phoenix trial. This study also reminds us that periprocedural MI
remains an important clinical event in the current era. Being
associated with increased risks of death at 30 days, and therefore
reducing ischemic events in patients undergoing PCI remains very
important.
The final paper describes experimental evidence of a novel
treatment approach to hypertension using micro RNA's. This paper is
from first author Dr. Lee and corresponding authors Dr. Chinn and
Wang from Tong G medical college and Whadrom University of Science
and Technology in Wuhan China.
Micro RNA's are a class of small non-coding RNA's that regulate
gene expression at a post transcriptional level. These authors
compared the expression of key neucler genoman coded and
mitochondrial genoman coded genes involved reactive oxygen species
production in spontaneous hypertensive rats and wistar rats. They
then used bioinformatics to predict the micro RNA targets followed
by biochemical validation using real time PCR and immunial
precipitation.
They first found that there was down regulation of mitochondrial
DNA encoded sitoca B in the spontaneous hyper intensive rats, which
appeared to directly contribute to the increased mitochondrial
reactive oxygen species.
Next they found that mere 21 a key micro RNA induced into hyper
spontaneous rats, was able to trans-locate into mitochondria to
counteract the mitochondria pseudonym B down regulation. Finally,
they showed that exogenous mere 21 delivered by recombinant adeno
associated virus was able to lower blood pressure and attenuate
cardiac hypertrophy in the spontaneously hypertensive rat
model.
These findings are striking because they provide experimental
support for developing micro RNA based treatments for
hypertension.
Those were your summaries of original papers but before I go, I
just have to highlight this in depth review paper in this week's
issue, and it is regarding sodium glucose co transported to
inhibitors or SLG2 inhibitors in the treatment of diabetes,
discussing the cardiovascular and kidney affects potential
mechanisms and clinical applications.
It is a beautiful review article written by first author Dr.
Heresphink of the University Medical Center Groningen,
corresponding author Dr. Churney from Toronto general hospital and
colleagues. Truly a must read, but now here is our featured
paper.
Our featured paper today is on patients with familial
hypercholesterolemia after acute cornery syndromes. Today I have
with us the first and corresponding author David Nan chin
university of Lausanne in Switzerland.
Hi David, thanks for joining us.
David:
Hi, I'm very happy to be here.
Carolyn:
As the associate editor who managed this paper we have Dr. Amat
Kira and you will recognise him as the digital strategies editor as
well from UT Southwestern. Welcome back Amat.
Amat:
Thank You Carolyn, happy to be here.
Carolyn:
I am really curious about this paper because it speaks of familial
hypercholesterolemia that most of us would assume is very rare.
Now David, I know that you actually published prevalence in a prior
paper last year, but could you maybe start by telling us why we
should, how common is this in our patients with acute coronary
syndrome?
David:
In fact we studied patients who is hospitalized with acute coronary
syndrome in several university hospitals in Switzerland. Of course
we try our best to include all classifications in the study in
order to be very protective of the acute coronary syndrome
population.
We found that among patients with acute coronary syndrome, familial
hypercholesterolemia was not a rare disease. We found a prevalence
of 2-5% which is in fact 10 times higher than what is thought to be
in the general population.
The important point here is that we use very simple clinical
catatonia to assist the prevalence of adage. This catatonia
includes unbelievable[inaudible 00:08:50] and the family of Bethany
of coronary heart disease. This criteria are very easy to use and
implement in a clinical practice in the sitting in acute coronary
syndrome to detect patients with familial hypercholesterolemia.
Carolyn:
Exactly. You did not use molecular diagnosis in your paper, but
yet, with these simple criteria there was a very important clinical
take home message. Could you tell us about those findings?
David:
The question we wanted to answer here is wanted to know what
happened to this patient with familial hypercholesterolemia after
hospital discharge. We found that patients with familial
hypercholesterolemia were an increased risk of recurrence of cornea
events within the year after discharge, and this is despite the use
of idol science.
In fact, one year after the coronary syndrome, 7 people found a
patient with adage were still using idle studies, which is very
good we were quite impressed by these numbers, but they
mean[inaudible 00:09:57] one year after the acute coronary
syndrome, with one in twenty become affected later.
Most of these patients were not able to decrease their added
cholesterol to lower evens.
I really think there is clear room for infestation of leamington
therapy among these patients. In any of those drugs available from
my seeing and very effective to decrease and [inaudible 00:10:25]
to substance, but they are very expensive.
Maybe the best initial strategy, to prescot these drugs, is to
target patients with familial hypercholesterolemia after acute
coronary syndrome. Because these patients are at high risk of
recurrence and most of them cannot achieve their cholesterol level
with our studies.
Carolyn:
Congratulations for being really the first to show that. This is
common and it affects recurrent events. I think actually the first
step is to recognize this in our patients which very few of us
really do I think.
Amat from your point of view, knowing the results of this paper how
has it changed your clinical practice?
Amat:
Absolutely Carolyn. First I congratulate Dr. Nan chin and his
colleagues. This was an incredibly important paper, and I think as
you pointed out, one of the first to really show us why it is
irrelevant to show us why it is relevant to identify FH at the time
of an ACS.
Generally even when I work with my trainees when we talk about FH,
everyone is thinking, "Well, we'll just put everyone on statins,"
and it's well appreciated. We can think about cascades swinging and
why it's important to their offspring, but what Dr. Nan chin and
his colleagues have certainly highlighted, is that these patients
are at higher risks for recurrent ACS and recurrent events, and
that's incredibly important as mentioned that tells us that maybe
the routine treatment post ACS with high dose statins is not
sufficient.
What's next is the tricky part, do we initiate PCS canine
initially, do we add a zedemi upfront. Sort of the next step is the
part that's a little bit more tricky, but I certainly see a
potential for augmented therapy in these patients up front.
Carolyn:
I like the way you said tricky, and that's usually when we call for
an editorial isn't it?
Amat:
That is correct as we will see with this article.
Carolyn:
I really like the title of it, "Diagnosis and Management of Petra
Zygas familial hypercholesterolemia too little and too late."
That was very interesting, but are there any other take home
messages from your end David?
David:
Maybe one thing we can add ... We are currently trying to change
our practice regarding these reasons that we have now. We have now
implemented in our casualty department a system that's explaining
strategy to identify this patient, to identify patient with
asage.
We have a prevention team that can provide very early during
hospitalization additional information for this patient about
asage. That's one very important point is to encourage family
testing especially for the children of the patient and also to
provide concerning for other cardiovascular risk factors. Because
we also found that half of these patients with asage were smokers
in fact and 40% of them had hypertension.
Certainly to address the other cardio risk factor in patients with
asage so certainly very important. At the end part of what we are
doing is we are assured of the patient will an appropriate medical
follow up in the primary care setting because it's also very
important for management of asage and circular prevention in the
primary care setting after discharge.
Carolyn:
Wow. Those are excellent points. Very practical advice on
screening, management, and really just applying the results of what
you found. Congratulations once again.
Amat I'm going to switch tracks a little bit now. Since we've got
you online I really have to ask you a couple of things with your
hat as a digital strategies editor.
Has it been two months since we first chatted even about this
podcast which is part of the digital strategies. Let's take stock
of it. How are things going?
Amat:
Well, so far I think excellent and frankly one of the highlights of
our digital strategies is your podcast. It's gotten rave reviews
and certainly appreciate all your enthusiasm and your unique take
on how to do this. We've also had some excellent work with our
social media. We have a revised website which has a lot more real
estate for some novel offerings, and I think we certainly can't
rule out traditional print media, but those articles that come out
online.
It's been really an exciting time and thinking of novel ways to
share new information in a modern era.
Carolyn:
Right. Thanks to you really Amat and I would really want to bring
out one of the strategies that we may have not talked about so
often yet, and that's the "on my mind" vlogs.
The reason I'm going to bring it up is because last week I was
struck by the on my mind article by Milton Packer and it's
entitled, "Heart Failure's Dark Secret. Does anyone really care
about optimal medical therapy?" That's just awesome. Could you tell
us a bit more about this vlog.
Amat:
I think you hit the nail on the head there it certainly an edgy and
controversial title, and if you think about it that's the purpose
of this in most of our academic writing. It's a little bit stiff in
following certain para dines, and more formal para view. The
purpose here for the on my mind was literally that for someone who
is a thought leader to free associate various ideas they have that
would be controversial or edgy or may not be accepted down the main
stream.
That's a bit on purpose because we hope to create a dialog around
that. If you look on our webpage, there's actually a place where
people can add comments or start a dialog saying whether they agree
or disagree, or begin an important conversation around these edgy
topics.
Carolyn:
I think that's the really cool part when we can actually start
interacting with our readers and listeners online that way.
Thank you to my wonderful guests and thank you listeners for
listening this week. Don't forget to tune in next week for more
highlights and features.