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 for the
National heart center and Duke National University of Singapore. Our podcast is
really going around the world, and today's feature interview comes to you live from
China. Where we will be discussing the prediction of ten year risks of cardiovascular
disease in the Chinese population. So now to all our Chinese colleagues out there:
Chinese dialect

First here's your summary of this week's journal. The first study challenges the
assumption that all patients with vascular disease are at high risk of recurrent
vascular events. First author Dr. Kasenbrud corresponding author Dr. Viceren and
colleagues form the University Medical center Utric in the Netherlands, provide
new data on the estimation of ten year risk of recurrent vascular events and a
secondary prevention population. In other words, in patients with established
cardiovascular disease they applied the second manifestations of arterial disease or
'smart' score for the ten year risk prediction of myocardial infarction, stoke or
vascular death in more than six thousand-nine hundred Dutch patients with
vascular diseases ranging for coronary artery disease, cerebral-vascular disease,
peripheral artery disease, abdominal aortic aneurysm and poly-vascular disease.
Predictors included in the SMART risk score included age, sex, current smoking,
diabetes, systolic blood pressure, total cholesterol, HGL cholesterol, presence of
coronary artery disease, cerebral-vascular disease, peripheral artery disease,
abdominal aortic aneurysm, estimated glomariaol fruition rate, high sensitivity CRP
and years since the first manifestation of vascular disease. They further externally
validated the risk score in more than eighteen thousand four hundred patients with
various types of vascular disease fro the TNT ideals Sparkle and Capri trials.

The overall findings was that the external performance of the SMART risk score was
reasonable apart from over-estimation of risk in patients which a ten year risk of
more than forty percent. What was striking was the substantial variation in the
estimated ten year risk. The median ten year risk of a reoccurring major vascular
event was 17 percent but this varied for less than 10 percent in 18 percent to more
than 30 percent in 22 percent of patients.

The authors further estimated residual risk at guideline recommend targets by

applying the relative risk reductions form meta-analysis to estimated risks for
targets for systolic pressure, LDL, smoking, physical activity and use of anti-
thrombotic agents. They found that if all modifiable risk factors were at guideline
recommend targets only half of the patients would have ten year risk of less than
10 percent. Even with optimal treatment many patients with vascular disease
appear to remain at more than a 20 percent or even more than 30 percent of a ten
year risk.

The take home message is that a single secondary prevention strategy for all
patients with vascular disease may not be appropriate. Instead novel risk
stratification approaches may be helpful to individualize secondary prevention by
identifying high risk patient which may derive the greatest benefit from novel
 interventions.

The next study provides experimental evidence that an indigenous-gastro

transmitter hydrogen sulfide may potentially be a therapeutic target in diabetic
patients with cardiovascular diseases. In this paper by first author Dr. Chen,
corresponding author Dr.Kisher and Colleagues from the Louis Cat's school of
medicine Temple University in Philadelphia. Authors aim to evaluate the role of
hydrogen sulfide deficiency in diabetes induced bone marrow cell dysfunction and
to examine the therapeutic effects of restoring hydrogen sulfide production in
diabetic bone marrow cells on ischemic high limb injury in diabetic DBDB mice.
They further specifically investigated the effects of hydrogen sulfide deficiency on
the nitric oxide pathways under conditions of high glucose. They found that bone
marrow cells for diabetic DBDB mice had decreased hydrogen sulfide production
and lower levels cystathonine gamma lyaze which is the primary enzyme that
produces hydrogen sulfide in the cardiovascular system. Administration of a stable
hydrogen sulfide donor and over expression of cystathonine gamma lyaze in
diabetic bone marrow cells restore their functional and restorative properties.
Further more they demonstrated that the therapeutic actions of hydrogen sulfide
were mediated by nitric oxide pathway involving endothelial nitric oxide synthase
PT495.

In summary these results support the hypothesis that hydrogen sulfide deficiency
plays critical role in diabetes induced bone marrow cell dysfunction and suggests
that modulating hydrogen sulfide production in diabetic bone marrow cells may
have transformational value in treating critical limbs ischemia.

The next study reinforces the importance of hypertension as a critical risk factor for
inter-cerebral hemorrhage, and suggests that Blacks and Hispanics may be a
particularly high risk. In this study by DR. Walsh and colleagues for the University of
Cincinnati, authors conducted the largest case controlled study to date on treated
and untreated hypertension as a risk factor for inter-cerebral hemorrhage. They
also investigated whether there was variation by ethnicity. The ethnic racial
variations of inter-cerebral hemorrhage or eriche study is a prospective multi-
center case controlled study of inter-cerebral hemorrhage among Whites, Blacks
and Hispanics. Cases were enrolled from 42 recruitment cites, controls were
matched cases one to one by age, sex, ethnicity and metropolitan area. A total of
958 white, 880 black and 766 Hispanic cases of inter-cerebral hemorrhage were
enrolled. Untreated hypertension was more highly prevalent in Blacks at almost 44
percent and Hispanics at almost 47 percent compared to whites at 33 percent.
Treated hypertension was a significant independent risk factor and untreated
hypertension was substantially greater risk factor for all three ethnic groups and
across all locations. There was a striking interaction between ethnicity and risk of
inter-cerebral hemorrhage, such that untreated hypertension conferred a greater
risk of inter-cerebral hemorrhage in Blacks and Hispanics relative to Whites.

The nest study provides the first prospective multi-centered data on mortality and
morbidity in rheumatic heart disease from low and middle income countries. First

COTR134_19 Page 2 of 7
 author Dr. Zulky, corresponding author Dr. Mayoci and authors from Gertrude
hospital and University of Cape Town in South Africa present the results of two
year follow up of the global rheumatic heart disease registry or remedy study in
3343 children and adults with rheumatic heart disease from 14 low and middle
income countries. They found that although patients were young with a median
age of only 28 years the 2 year case fatality rate was high at almost 17 percent. The
median age at death was 28.7 years. Mortality was higher in low income and low
middle income regions compared to upper middle income countries. Independent
predictors of death was severe valve disease, more advanced functional class, atrial
fibrillation and older age. Where as post primary education and female sex were
associated with a lower risk of death. The authors carefully noted that apart from
age and gender the independent risk factors for mortality such as severity of valve
disease heart failure, atrial fibrillation and low education were all modifiable and
thus they called for programs focused on the early detection and treatment on
clinical rheumatic heart disease.

Well that's it for the summaries, now lets go over to China

For our feature interview today we are going all the way to Beijing at the great Wall
meeting where we will be meeting authors as well as editors. So here we have first
and corresponding author Professor {Dong Fen Gu} and co-author Professor
{Sherliang} both from {Fu Y} hospital Chinese academy of medical sciences in
Beijing. Welcome

Dr.Gu: Welcome we are so delighted to be interviewed by you

Dr. Carolyn Lam: Thank you so much we are so excited to be talking about your paper predicting the
ten year risks of cardiovascular disease in the Chinese population. And here we
have as well editor in chief Dr. Joe Hill as well as Dr. Amid Kira digital strategies
editor and associate editor. Gentlemen how is it in Beijing? And I hear that you
have a Chinese greeting for everyone as well.

Joe Hill: {Ni how} and {nuchme and senchmen}

Amid Kira: I can't top that but I agree with what Joe said

Dr. Carolyn Lam: Dr. Gu, could you please tell us what is it that is so different about cardiovascular
disease in China compared to what we heard about in the western world.

Dr.Gu: Okay cardiovascular disease is both leading cause of death in China and in United
States as well in European countries. However the patterns for components of
cardiovascular disease including coronary arteries and stroke are still quite
different in the Chinese populations compared united states. For example there are
coronary arteries mortality rate in the united states is along the 100 thousand per
year and this is the first leading cause of death in the united states. And for stroke
the annual mortality rate is along 36 per 100 thousand in the united states
populations. However in china the stroke mortality rate among Chinese

COTR134_19 Page 3 of 7
 populations is around the 160 per 100 thousand, so that almost 3.5 to 4 as high as
in untied states. Obviously for our lifestyle in including battery behavior quite
different you can easily identify one kind of difference in the united states and the
Europe restaurants from Chinese restaurants and some western style restaurants
you can figure it out.

And another example, smoking rate is major component for risk of cardiovascular
disease it is very high in Chinese adult men. It over 50 percent right now but in the
united states in the past 50 years it declined immensely. And around maybe less
than around 20 percent and from the previous experiment from studies by Dr. Liu
Chin from and my colleague Dr.WU they used the questions for predictions of
coronary arteries compared to equations and also use the similar prediction model
compares that its chemical cardiovascular disease from the united states
population and the Chinese population. That to over estimation if we use the
united states produced this kind of equation. So based on this kind of scenario we
based on Chinese long term larger scales cohort to precede and study our own
prediction model.

Dr. Carolyn Lam: Wow that is really fascinating Dr. Gu and I really could not agree with you more
because I sort of trained in the united states for quite some time and then I moved
back to Singapore and saw for myself in Asia the tremendously high rates of stroke.
I was also very struck by the relative youth of the patients suffering cardiovascular
disease and the differences in risk factors, the smoking but not just that, obesity is
almost defined on a different scale in our relatively sized smaller Chinese
population compared to that in the western. Congratulations to you and your team
for a successful amazing effort. Could you or Dr. Yang now just let us know what
are your main findings.

Dr. Yang: Well I think there are 2 major finding for our work. First we developed a new
prediction risk model you know after analysis is for high risk score or equations
released by AJ and ACC and is some other risk scores. We included 6 conditional
risk factors in combination with our previous knowledge that included age, treated
or untreated ISBP, total classical, HDLC current smoking and diabetes. So this
traditional risk factors were set up as a base model and then we use the predefined
statistical to include new additional variables they were Chinese special elements.
Finally in our model there were rates as constraints and geographic region which
means northern part versus the southern part in China and also organization is
rural or urban area. And finally the forth one is family history as a CVD so this for
additional variables in our model suggest that we maybe as a Chinese prediction
and equations has something special. For example we feel more attention for
central obesity in primary prevention in Chinese populations and also you know the
norther part and the southern part there are large differences in the risk profiles.
And so maybe according to our risk prediction model we pay more attentions for
the residence living in northern part in China.

And then for the second points I think we found that PCE equation which shows for
equations was not appropriate to predict ten year risk of in Chinese populations.

COTR134_19 Page 4 of 7
 For example in our revelation cohort we found that our model just slightly over
predicts severity risk by 17 percent in Chinese man but when we use the PCE
models released form AHA the over-estimation come to 50 percent so maybe
equations from western populations are not appropriate to Chinese populations.

Dr. Carolyn Lam: Thank you so much Dr. Yang I mean those are just such important findings
applicable to a huge population in china, like you said. And just as important as the
second point that the pooled equations derived from western populations may not
be the most appropriate for certain other ethnic populations. I think that a very
important message and that why we are so proud to be publishing this in
Circulation. Could I ask then are you applying these new equations in your personal
clinical practice?

Dr.Gu: Risk assessment is a fundamental components for prevention of ASSVD. In Chinese

we question {turn the PA on} provide a valuable to identify high risk individuals in
Chinese populations. And not with just complicated [inaudible 00:18:02] for further
analysis. And propose three levels of groups of risk stratification could be identified
by cut off 5 percent and 10 percent. So lower risk individuals with predicted activity
risk of less than 5 percent should be offered lifestyle wise to maintain the lower risk
status. While the moderate risk individual is predicted risk of 5 to 10 percentage for
intensive therapeutic lifestyle change wit drug therapy if necessary. For the high
individual risk high or large 10 percent teheraph of clinical aliment taken account
for physicians recommendation should be required with therapy for the lifestyle
modification. Then annually clinic up, including an echocardiographic information
for carotid artery back and even for outer [inaudible 00:19:09] CT examinations for
coronary artery are recommended. Also blood pressure, lipids, glucose
measurement if necessary are suggest according to Chinese guideline. While
cardiovascular disease prevention as well as for the epidemic of this kind a lines.
For ACVD patients those are different kinds of risk assessment we could know
whether their risk profile had been improved or be progressed so that appropriate
clinical elements should be taken in clinical practice.

Dr. Carolyn Lam: Thank you very much Dr. Gu so that just show that these findings are immediately
clinically applicable and I trust that means you're suing it in your clinics too, and
once again were so happy to be publishing this in Circulation so in the rest of the
time in going to now direct questions at Joe and Amid.

How's China been? How are your chopstick skills and any word on how Circulation
is being received there?

Joe Hill: Well Carolyn its a delight to be here this is a bustling media that get better and
better every year. In about 2 hours we have our first ever Circulation session, we
brought several editors here to discuss the types of content that we are looking to
publish, the type of work across prevention and population and electrophysiology
of heart failure. This is an extraordinary media that is now internationally acclaimed
and as we've heard here, the face of cardiovascular disease in Asia is changing. And
as you pointed out 60percent of the human race lives in Asia and we want to do

COTR134_19 Page 5 of 7
 everything we can to be here on the ground, in Asia trying to address this curve
that is already present and is worsening by the day.

Dr. Carolyn Lam: Amid, you know you've seen the latest statistic on our podcasts and you
highlighted that we have quite a number of listeners over there as well. Would you
like to tell me how this is all blending it to the digital strategies and anything else
you might want to highlight?

Amid Kira: Sure its been an incredible meeting and we get to meet great colleagues like our
colleagues today on this podcast and learning so much from this meeting. Our
podcast as you pointed out quite a sizable and growing cadre of people in Asia and
Japan and China who are listening and we truly want to enhance that as Joe
mentioned with the large splurge of cardiovascular disease and the great science
that is going on here. Want to make sure that we are able to be apart of that
conversation and interact with researcher and clinitions here. In addition to
podcast, we are exploring some other options involving social media, specifically in
China so stayed tuned in how those develop but we certainly appreciate the
importance of being her and interacting where so much of cardiovascular disease
and cardiovascular science is occurring.

Dr. Carolyn Lam: That's so great. Joe or Amid now there's a specific we would like to highlight to our
listeners the doodle, either of you want to pick that up a bit about blipping the
doodle?

Amid Kira: So there is as you know Circulation now has this doodle where we change it
periodically and its sort of a fun themed thing. Right now I think it Halloween and
we've had several other ones that people have designed to sort of keep thing fresh
and light and interesting. There's a new app called blippar which you can download
from iTunes or android stores and you can essentially scroll that over with your
phone with the doodle and that will take you to new content either table of
contents of videos, different kinds of content that it can navigate you to. So I hope
people will not only enjoy the doodle kind of anticipate what's next in terms of
seasons but will take the time t blip the doodle when they get a chance.

Dr. Carolyn Lam: That great and that blippar- B l I P P A R. You really c should check it out, anyone
who is listening to this really check it out you'll be floored. Joe could I just turn the
mic to you for any last words about the global outreach of Circulation, I mean its
just so amazing that you're there in China

Joe Hill: Well heart disease Carolyn knows no boundaries nor does Circulation. There was a
day when cardiovascular disease was largely an issue in the developed world that is
long since gone and that's why the study that we are talking about today with these
authors is so important because the face of cardiovascular disease is different than
in the west, the ways in which it is evolving id different here than in the west and I
like many others foresee an increase a significant increase in the types and
prevalence of heart disease here in Asia. for all the reasons that we have been
talking about, hypertension, obesity, type two diabetes, smoking the environment

COTR134_19 Page 6 of 7
 all of these challenges I fear are going to lead to a substantial increase in the
prevalence of heart disease in Asia and that why we're here on the ground with
Circulation in Asia that's why we have one of our major leaders Chong Shong Ma
who is here in Beijing. Circulation is in China everyday, it’s in Beijing everyday to try
and address this problem.

Dr. Carolyn Lam: And you heard it from our editor and chief, so thank you everyone for listening to
this episode of Circulation on run. Tune in next week.

COTR134_19 Page 7 of 7