Circulation September 6, 2016 Issue

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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.

Hi, I'm very happy to be here.

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.

Thank You Carolyn, happy to be here.

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?

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.

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?

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.

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?

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.

I like the way you said tricky, and that's usually when we call for an editorial isn't it?

That is correct as we will see with this article.

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?

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.

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?

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.

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.

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.

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.

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