Circulation March 10, 2020 Issue

Dr Carolyn Lam: Welcome to Circulation On The Run, your weekly
podcast summary and backstage pass to the Journal and its
editors. I'm Dr Carolyn Lam, associate editor from the National
Heart Center and Duke National University of Singapore.


Dr Greg Hundley: And I'm Dr Greg Hundley, Director of the Pauley
Heart Center at VCU Health in Richmond, Virginia. Well, Carolyn,
the feature article today is really interesting. It's evaluating
the evolution of cardiovascular disease associated adverse events
in developing countries and It's really fascinating looking at
differences between Russia, China, India, and Brazil, but more to
come. Don't want to spoil all that. How about we get started with
a cup of coffee and discussing some of the articles in the
Journal.


Dr Carolyn Lam: You bet, Greg. Well, I want to start off with
this paper that provides really novel insights into the
pathogenesis of hypertrophic cardiomyopathy.


Dr Greg Hundley: Carolyn, you're one of the cardiomyopathy
experts. Can you give us a little background before we get
started?


Dr Carolyn Lam: Not sure about expert, but I can sure give you a
background. So. Hypertrophic cardiomyopathy remember, is caused
by pathogenic variants in the sarcomere protein genes, and that
evokes hypercontractility, poor relaxation, and increased energy
consumption by the heart and increases the patient's risk for
arrhythmias and heart failure. Recent studies show that the
pathogenic missense variants in myosin are clustered in residues
that participate in dynamic confirmational states of the
sarcomere proteins.


In today's paper from co-corresponding authors Dr Seidman and
Toepfer from Harvard Medical School, authors hypothesized that
these confirmations were essential to adapt contractile output
for energy conservation and that pathophysiology of hypertrophic
cardiomyopathy resulted from destabilization of these
confirmations.


So they assayed myosin ATP binding to define the proportions of
myosin in two confirmational states called SRX or DRX. This was
done in healthy rodent and human hearts at baseline and in
response to reduced hemodynamic demands of hibernation or
pathogenic hypertrophic cardiomyopathy variants.


They found that hypertrophic cardiomyopathy mutations that
disrupted the physiologic balance of SRX and DRX altered
cardiomyocyte contraction, relaxation and metabolism, and
conveyed increased risk for heart failure and atrial
fibrillation. In fact, a small molecule could restore the
physiologic balance of SRX and DRX and improve functional
energetic and cellular abnormalities that occurred in
hypertrophic cardiomyopathy.


Dr Greg Hundley: Very interesting, Carolyn. Well, let me tell you
about my paper. It's called The OUTSMART Heart Failure. It's a
randomized controlled trial of routine versus selective use of
cardiovascular magnetic resonance for patients with non-ischemic
heart failure. And it's from Dr David Ian Paterson at the
University of Alberta.


This is a study from Canada randomizing 500 patients with
suspected non-ischemic heart failure to either having a cardiac
MRI as the first imaging study or have an echo, and then based on
the echo, order an MRI if the physician so indicates. It was an
older version of MRIs, so it's a SUNY assessment of function,
including the EF, and then delayed enhancement, a technique that
again has been available for the past 20 years and incorporates
gadolinium contrast.


Dr Carolyn Lam: Greg, this is so unfair. I'm an echo person,
you're an MRI person, but you get to tell us the results and
inject your thoughts.


Dr Greg Hundley: No bias. So, Clinical outcomes, Carolyn, you'll
be very appreciative, were similar for the two groups of
subjects, although the heart failure etiology was more frequently
derived in those that received an MRI, whether you're randomized
to an MRI first or if you had an echo and they said, "Oh, go get
an MRI." The patients with specific heart failure etiologies from
imaging had worse outcomes, whereas the heart failure etiologies
defined clinically did not.


So, if you didn't take the imaging into account, it didn't
discriminate. Importantly, the authors note that more modern
techniques, involving mapping with or without contrast, were not
employed. It's an older form of the MRI imaging, but the results
would suggest that physician decisions regarding the potential
use of MRI are important. Bringing us in to decide when to get it
is a good idea based on these results.


Dr Carolyn Lam: That was very balanced. Thank you, Greg. But I've
got a question for you now. What do you think of coconut oil? Do
you take it?


Dr Greg Hundley: Well, I love coconut cake. Does that count?


Dr Carolyn Lam: Well, I have to tell you, I cannot even begin to
name the number of people, it's friends and relatives and
patients, who take coconut oil because they believe it's good for
them. They literally spoon it into their mouths. The truth is
coconut oil has been accorded much attention in the popular media
as a potential beneficial food product. In fact, a survey in 2016
found that 72% of Americans viewed coconut oil as a healthy food.
This represents a remarkable success in marketing by coconut oil
and related industries calling coconut oil a natural healthful
product despite its known action to increase LDL cholesterol. Of
course, we know that, that's an established cause of
atherosclerosis and cardiovascular events.


This paper in our journal really deserves attention. It's from
corresponding author Dr Rob van Dam from Saw Swee Hock School of
Public Health and the National University of Singapore. He and
his colleagues conducted a systematic review of the effect of
coconut oil consumption on blood lipids and other cardiovascular
risk factors compared with other cooking oils using data from
clinical trials. In a meta-analysis of 16 trials, they found that
coconut oil consumption significantly increased LDL cholesterol
concentrations as compared with non-vegetable oils. Although
coconut oil consumption also increased HDL cholesterol
concentrations, we need to remember that efforts to reduce
cardiovascular risk by increasing HDL, have not really been
successful in the past.


Anyway, there was no evidence of benefits of coconut oil over
non-tropical vegetable oils for adiposity or glycemic or
inflammatory markers. Now, this is discussed in an editorial by
Dr Frank Sacks at Harvard T.H. Chan School of Public Health and
it's entitled: “Coconut Oil and Heart Health. Fact or Fiction?”


Dr Greg Hundley: Very nice, Carolyn. Well, I guess I can't use my
coconut cake to lower my LDL. How about we get on to what else is
in the journal? You want to go first?


Dr Carolyn Lam: Yeah. We have an important white paper by Dr
Sharma on the impact of regulatory guidance on evaluating
cardiovascular risk of new glucose lowering therapies, to treat
type two diabetes. It talks about lessons learned and future
directions. All of this was occurring in February 2018 when a
think tank comprising representatives from academia, industry,
and regulatory agencies convened to consider the guidance in
light of findings of the completed CV outcome trials. Very, very
important read. We also have a research letter from Dr Wanken
entitled, “Characterization of Endovascular Abdominal Aortic
Aneurysm Repair Surveillance in the Vascular Quality Initiative.”
You got to read about that.


Dr Greg Hundley: Well, Paul Ridker writes a very nice perspective
piece. Will all atherosclerosis patients soon be treated with
combination lipid lowering and inflammatory inhibitors? Very
interesting read. In a separate article, there's a nice ECG
challenge from Dr Andrei Margulescu, An Irregular Tachycardia
that's not Responsive to Medical Treatment: What is the
Diagnosis? A great read for those in training.


Got a couple letters to tell you about. One is the research
letter on filamin-C and it's essential for heart function from
Professor Ju Chen University of California, San Diego. Then,
there's a letter to the editor regarding the article, Stroke Risk
as a Function of Atrial Fibrillation Duration in CHA2DS2-VASc
Scores from Dr Ming-Wu Xia from Hefei Affiliated Hospital and
Anhui Medical University. Then there's a response letter from Rod
Passman from the Feinberg School of Medicine at Northwestern
University. Well, Carolyn, how about we go to learn about the
evolution of cardiovascular events and how they're evolving in
Russia, China, India, and Brazil.


Dr Carolyn Lam: Super excited about this one. Let's go, Greg. Our
feature paper today focuses on cardiovascular disease burden in
the BRICS, and that stands for Brazil, Russia, India, China, and
South Africa, B. R. I. C. S. Which is a grouping of upper and
lower middle-income countries constituting almost half the
world's population and contributing almost a third of the world's
GDP. A really, really important paper here. I'm so pleased to
have with us the corresponding author of this paper, Dr Zhiyong
Zou from Peking University School of Public Health.


Dr Jo, can you please start by telling us a little bit about how
you did this study? I thought the methods were amazing.


Dr Zhiyong Zou: There was little study on cardiovascular disease
in breaks. So most of the studies have focused just fatality
across year, and then reported change in different age groups.
However, this fails to distinguish cohort from period effects. So
our study aims to examine the time change and also the relative
contribution of period and cohort facts.


Dr Carolyn Lam: Wow. So that's big and an acute area. So could
you tell us a little bit more about how you did this? Like the
databases and then some of the very interesting methodology such
as net drift, age curves, period, relative effects. Could you
maybe describe those?


Dr Zhiyong Zou: The data was derived from global burden disease
2017 which was as estimate by the university of Washington. This
data was estimate for the whole population in each country from
many original data sources. Our study used a new method, age
period, cohort model.


We can use this model to estimate first cohort from period
effects so we can compare different post cohort population and
the different period population. They have different effects. And
also, we can estimate the net drift, net drift is the overall
annual percentage change. It is different from other study. Just
to calculate the average percentage change. It is different. It
was adjusted for period effects.


Dr Carolyn Lam: Audience, I really have to refer you to the
figures of this paper. They're beautiful and that really...
Pictures say a thousand words, but Dr Zou, could you now tell us
what were the key findings?


Dr Zhiyong Zou: First, although there have been reductions in the
breaks of the CVD mortality, they have lagged behind North
American by over 15%. Yes, it is very decreased slowly but there
is a notable exception of Brazil and the second, there was
striking difference between countries. Russia consistently has
the highest CVD mortality and Brazil have the lowest. Brazil and
China have had continuing vitality improvements since 1992 but
there has been little decry in India for middle age Indian males.
CVD mortality has increased.


The last one is China has a high rate of out of hospital ischemia
heart disease test reflecting poor pre-hospital care. Only 11% of
the out of hospital desks received a basic cardiopulmonary
citation. And the yes in China, this situation is very serious.


Dr Carolyn Lam: So really fascinating results. And maybe I could
just add that you observed over a 25-year period from 1992 to
2016 the general picture is at least there's a decline in these
areas, but definitely not as much as that observed during the
same time in North America. But I absolutely agree that the
striking country differences, so you know, maybe we should start
with something positive. Dr Zou, what lessons do you think we
could learn from Brazil's strikingly exceptional example?


Dr Zhiyong Zou: Brazil stands out for successful epidemiological
transition. Yes, they with a rapid reduction. There are two
important factors: The first one is Brazil investment in health
with a decrease in smoking from 13.5% in 1999 to 17% in 2009 it
decreased by 15%. Another factor is Brazil reform of primary
health care focus on the family health program and the prevention
and the care for the management of SADs.


Dr Carolyn Lam: I like that. From this paper we could get very,
very important public health messages that may inform countries
on how this burden can be tackled better like that. Good example
of Brazil, but now maybe the tougher topic of in China, what do
you think is the reason for the continuing problem with ischemic
heart disease


Dr Zhiyong Zou: In China? The real mortality of ischemia heart
disease increased very quickly, around 13.5% Increase. Compare
that with other countries or declined. So in China with that,
there were about 300 million more smokers in China. It was the
biggest number in the world? Yes. So it's a big challenge for the
government to control the smoking rate. And also, we mentioned
that only 11% of the outside hospital Does received a
cardiopulmonary citation.


Dr Carolyn Lam: Yeah. And so the point about the low CPR rates
may point to more systematic issues in a primary care and public
setting, isn't it? And it must be so difficult in a place as huge
as China with such diversity in rural communities versus urban
and so on. So very important points. I mean, do you have any
insights for the issues that are seen in, for example, South
Africa, Russia and India?


Dr Zhiyong Zou: We don't have data from the other countries.


Dr Carolyn Lam: Sure. One postulation I suppose thinking about
things could be just very rapid transition from the era of
infectious disease, communicable diseases to noncommunicable
diseases. But you know, the diversity even among those is really,
really astounding.


And I think everyone really just has to pick up your paper and
have a good read. So could I ask, what are some of the take home
messages and next steps that you may have in further research?


Dr Zhiyong Zou: The take home message is, Brazil's success
suggest that the prevention policies can both reduce the risk for
younger both cohorts and also, the greater risk for all age
groups indicating greater progress in achieving CVD health is
possible in rapid three in merging economics, which provide
example for China and for India. And also a failure to
investigate CVD prevention in countries undergoing rapid economic
change will exert huge human and economic costs. So that's the
take home message.


Dr Carolyn Lam: And those are great, great summaries. And do you
have personal plans for further research in this area?


Dr Zhiyong Zou: Yes. In future, we will forecast on the risk
factors because in this paper we find many priority age groups in
different countries like example, in China those aged over 15
years old, is the prime priority age groups. But in India, 35-60
years old is the most priority age group because in these people,
they are most of the productive age, but the mortality increased
very quickly.


Dr Carolyn Lam: Yeah, a very good point. And investigating those
risk factors would be so informative. Well, thank you so much, Dr
Zou for sharing your incredible work with us. We're so proud to
be publishing this important work.


Thank you, audience, for joining us today. You've been listening
to Circulation on the Run. Please tune in again next week.


Dr Greg Hundley: This program is copyright, the American Heart
Association 2020.