Circulation September 6, 2016 Issue

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.