Jul 25, 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 Lam,
Associate Editor from the National Heart Centre and Duke National
University of Singapore. I am so excited to be joined in just a
moment by Dr. Andrea [inaudible 00:00:21] and Dr. Wendy Post to
discuss the feature paper this week about leisure-time physical
activity and the risk of coronary heart disease in young women.
First, here's the summary of this week's issue.
The first paper, by Dr. Bohula and colleagues at the TIMI Study
Group at Brigham and Women's Hospital in Boston, Massachusetts, aim
to test the hypothesis that an atherothrombotic risk stratification
tool may be useful to identify high-risk patients who have the
greatest potential for benefit from more intensive secondary
preventive therapy such as treatment with Vorapaxar following a
myocardial infarction. As a reminder, Vorapaxar is a first-in-class
anti-platelet agent that inhibits thrombin-mediated activation of
platelets via the protease activator receptor 1. The authors
studied almost 8,600 stable patients with a prior myocardial
infarction followed for a median of two and a half years.
In the thrombin receptor antagonist and secondary prevention of
athrothrombotic ischemic events, TIMI 50 trial. They identified
nine independent risk predictors which were age, diabetes,
hypertension, smoking, peripheral artery disease, prior stroke,
prior coronary bypass grafting, heart failure and renal
dysfunction. A simple integer-based scheme using these predictors
showed a strong graded relationship with the rates of
cardiovascular death, myocardial infarction or ischemic stroke.
Moreover, the net clinical outcome was increasingly favorable with
Vorapaxar across the risk groups.
In summary, this paper provides a practical strategy that could be
used by clinicians to assist with risk stratification and
therapeutic decision-making regarding Veropaxar use for secondary
prevention after myocardial infarction.
The next paper is by first author Dr. [inaudible 00:02:40] and
corresponding authors, Dr. [Gerstein 00:02:43] from the Beth Israel
Deaconess Medical Center and Dr. [Carr 00:02:47] from the Broad
Institute of Harvard and MIT, who look at aptamer-based proteomic
profiling. Now DNA aptamers are [alu 00:02:57] nucleotides of
approximately 50 base pairs in length selected for their ability to
bind proteins with high specificity and affinity. They therefore
holds considerable promise for biomarker and pathway discovery in
cardiovascular diseases.
These authors applied a novel technology that uses single-stranded
DNA aptamers to measure over 1,100 proteins in a single blood
sample. They applied this to a model of planned myocardial injury
and that is patients undergoing septal ablation for hypertrophic
cardiomyopathy, and they found that 217 proteins were significantly
changed in the peripheral vein blood after planned myocardial
injury in this derivation cohort. They validated 79 of these
proteins in an independent cohort. Furthermore, among 40 validated
proteins that increase within one hour after myocardial injury, 23
were also elevated in patients with spontaneous myocardial
infarction.
Finally, the authors applied this to archive samples from the
Framingham heart study and showed 156 significant protein
associations with the Framingham risk score. This study is so
exciting because it highlights any merging proteomics tool that
captures a large number of low abundance analytes with high
sensitivity and precision, thus providing important proof of
principle for future clinical applications and this is discussed in
an excellent editorial that accompanies this paper by doctors
Graham [Malini 00:04:37], [Lau Enleui 00:04:39] from the University
of Ottawa Heart Institute.
The next paper is by Dr. [Anter 00:04:51] and colleagues from the
Beth Israel Deaconess Medical Center in Boston, Massachusetts, who
looked at post infarction, reentrant ventricular tachycardia and
addressed the problem that in vivo descriptions of ventricular
tachycardia circuits are currently limited by insufficient
spatiotemporal resolution. The authors therefore utilize a novel,
high resolution mapping technology to characterize the
electrophysiological properties of these reentrant circuits in 15
swine.
The main finding was that the zones of slow conduction within the
reentrant circuits with the inward and outward curvatures while
conduction velocity in the comment channel isthmus itself was
nearly normal. The authors further demonstrated that entrainment
mapping over estimated the true size of the isthmus. Thus, the
conclusion was that high resolution activation mapping of
ventricular tachycardia may better guide ablation therapy and
ablation at zones of high curvature may be an attractive target for
ablation.
The final papers from first author, Dr. [Tang 00:06:08] and
corresponding author Dr. [Fitzgerald 00:06:10] from the University
of Pennsylvania Perlman School of Medicine in Philadelphia. These
authors studied the cardiovascular consequences of prostanoid
I-receptor deletion in microsomal prostaglandin E synthase-1
deficient hyperlipidemic mice. The clinical background to this
research question is that inhibitors of cyclooxygenase-2 or Cox-2
are well-known to relieve pain, fever and inflammation by
suppressing biosynthesis of prostacyclin and prostaglandin E2.
However, suppression of these prostaglandins particularly
prostacyclin by Cox-2 inhibitors or deletion of the I-prostanoid
receptor for prostacyclin is known to accelerate atherogenesis and
enhance thrombogenesis in mice. In contrast, deletion of the
microsomal prostaglandin E synthase1 has been shown to suppress
PGE2 but increase biosynthesis of prostacyclin. It therefore
confers analgesia while attenuating atherogenesis and does not
predispose mice to thrombogenesis. Therefore, possibly contributing
to cardiovascular efficacy.
In this particular study, therefore, the authors sought to
determine the relative contribution of suppressing PGE2 versus
augmenting prostacyclin to the impact of depletion of microsomal
prostaglandin E synthase-1 in hyperlipidemic mice. The main
findings were that augmentation of prostacyclin is the dominant
contributor to the favorable thrombogenic profile of microsomal
prostaglandin E synthase-1 depletion in these atherosclerotic mice
while suppression of PGE2 accounted for the protective effects in
atherosclerosis and the exciting clinical take-home message is that
inhibitors of the microsomal prostaglandin E synthase-1 may be less
likely to cause cardiovascular adverse effects than NSAIDS or
specific inhibition of Cox-2. Those were the highlights of this
week. Now for our feature paper.
Our feature paper today is entitled "The frequency, [type 00:08:41]
and volume of leisure time physical activity and risk of coronary
heart disease in young women" and I am so excited to be joined by
two lovely ladies today to discuss this paper. First, the first and
corresponding author Dr. Andrea [Comastick 00:08:58] from the
School of Public Health of Indiana University Bloomington and Dr.
Wendy Post, associate editor from the Johns Hopkins University.
Welcome Andrea and Wendy.
Andrea:
Hi. Thanks.
Wendy:
Thank you so much for having us.
Carolyn:
I am just so excited that we are talking about a paper about women
being discussed by women. What more could you ask for? I have to
say this is a first for Circulation on the Run, which is why I’m
just so excited, so let’s get straight into it.
Andrea, maybe I could just ask you to start by sharing the story of
how you and your team came up with some new questions and new data
because I’m sure a lot of listeners are thinking there’s a lot of
data on exercise and how good it is for cardiovascular health in
women already.
Andrea:
Yeah, that's a great question. When we started talking about
conceptualizing this paper, the first thing was to focus on younger
women. Most of the previous work on physical activity and heart
disease has been in older adults and that's primarily because it's
older adults that have heart attacks. It’s hard to get a large
enough study of young women that has enough coronary heart disease
events to be able to study this. We were fortunate where we had a
large cohort in the nurses health study too of women and because
it’s been followed for over 20 years, we had enough events to be
able to examine this association.
We did want to think about, "Okay, what can we add?" because
there’s a lot of information about just overall physical activity
and health, so what can we do differently? I’m pretty familiar with
the physical activity guidelines and really tried to look at what
in the guidelines currently and then what could we add? What could
be of interest when they start revising the guidelines which is
actually going to happen very soon.
That was when we started focusing on, "Okay, instead of looking at
just overall activity, look at intensity, comparing moderate and
vigorous." We also wanted to look at frequency of physical activity
and looking at frequency but also adjusted for a total time or
total amount of physical activity that somebody does. Then we are
also, the third thing was that we thought was important was looking
at adolescent physical activity.
We know that kids, unfortunately as they get older and get into
their teenage years, their activity declines quite a bit. Looking
at how this physical activity during adolescence earlier life
impact coronary heart disease risk in adulthood. Those were the
three main things that we were focusing on when we first
conceptualized the paper.
Carolyn:
Nice. Tell us, what did you find?
Andrea:
We did find that exercise is just as beneficial in younger woman as
it is in older adults, which is great. We also found that moderate
intensity exercise is just as beneficial as vigorous intensity
exercise, which I think is a really important message to get out
there. I think a lot of people, especially those that are really
inactive to begin with are completely intimidated about the fact of
trying to think about going to a gym or trying to jog or run a
marathon or something like that.
I think really emphasizing that moderate intensity activity is
beneficial and we found that walking was actually the most
beneficial activity that we looked at in our study, that brisk
walking was really really good for everybody and really lowered
risk of coronary heart disease.
Carolyn:
Hooray.
Andrea:
Yeah, and the other thing we found which might be of interest for
those that are also extremely busy, especially this target
population where a lot of people are moms and working was that
frequency didn't seem to matter, that as long as people were
exercising for a couple hours a week that they should be that they
could accumulate it in a couple times a week or they could do it
more frequently, four or five times a week. It didn't seem to
matter.
Carolyn:
That’s cool. You know what? I think a lot of these things we'll
also discuss at the Editorial Board when we're looking at this
paper. Wendy, we promised that we would give a backstage pass to
the Editorial Board and The Journal, so could you share a little
bit about what we talked about there?
Wendy:
Well, the Editorial Board was really excited about this paper. We
loved the emphasis on young women and the important public health
message about how we need to get out there and move and exercise to
reduce our risk for cardiovascular disease. As was mentioned, there
have been previous studies that also show the benefit of exercise
but the Editorial Board especially liked the large sample size, the
long duration of follow-up, the number of events that had been
accrued that allowed for sophisticated analyses, adjustment for
confounders and the very rigorous study design and excellent
statistical methods that have been used in this study and so many
other studies from the nurses health study, but I think we
particularly just loved the message. The message was great.
We need to get out there and move. We need to tell our patients,
especially young women, that now we have data that if you start
exercising now, it will help in the future but also the study
showed that if you hadn't exercised much in early life that’s
starting to exercise more proximal to the event was also important
as well.
Carolyn:
Thank you Wendy. I also remember that we talked about the lack of
interaction with body mass index, and I thought that was a great
message. Andrea, could you maybe share a little bit about that?
Andrea:
Yeah, this is something that previous investigators have looked at
the interaction between body mass index and exercise.
Unfortunately, we’ve all found the same thing so it doesn’t seem to
matter whether women are normal weight or overweight or obese that
they still get benefit when they exercise, and I think that’s
really encouraging. I know a lot of people might start to exercise
because they really want to drop some weight but just trying to
emphasize even if the numbers on the scale aren't changing, that
exercise still has all these really great benefits for heart
disease and also for many other diseases.
Carolyn:
Exactly. Can I just ask both of you and maybe I’ll start with
Andrea, what will you do different now both as a woman and as a
clinician seeing women now that you know what you do from your
data?
Andrea:
Well, I’m not a clinician. I’m an epidemiologist so unfortunately I
don’t get to see patients and counsel them although I do try to
talk to community members as a public health person and really get
in the community on board with what we’re talking about. I just try
to tell people, I actually talked to a group of people last week,
and just trying to say, "Anything is better than nothing and just
trying to even start with some short walks." Again, just
emphasizing you don’t have to go to a gym or you don’t have to be
doing anything that's super strenuous but just do stuff that feels
good and just try to get your heart rate up a little bit like going
out for a brisk walk. I think that's my main message that I try to
tell everybody is at least start with something and get moving a
little bit.
Carolyn:
I love that. Wendy?
Wendy:
I like to emphasize the data about brisk walking. I thought that
was great because many of our patients don’t want to join a gym,
don’t have the time to join a gym so just getting out and walking
is fabulous exercise and now we have the data here that in young
women that after 20 years of follow-up, brisk walking was
associated with I think it was a 35% reduction in risk for
cardiovascular disease during follow-up.
In addition, I liked the message about the total amount of time
that you spend exercising in a week is what’s important. It doesn’t
matter whether you divide that into seven days a week to get to
that same amount of time or whether you do it in bursts of three
days a week, and I think that’s particularly important for the many
women who have so many different responsibilities and may not have
time every day to go out and exercise. The days that you do have
time, just exercise a little bit more those days, so lots of really
important messages for our patients and for ourselves.
Carolyn:
I really couldn’t agree more and just from my point of view,
because I see a lot of patients in Asia and I do acknowledge just
like you did, Andrea, in your paper that your data are
predominantly in white populations. Still one of the messages I
like to get out to the women I see is we have very skinny women and
when I see younger women, and I really like emphasizing that, "Hey,
just because you’re not struggling with an obesity issue or just
because you’re young, it doesn’t mean you don’t need to exercise
and that we all should just get moving." Thank you very, very much
for that Andrea.
Andrea:
Oh, no. It's my pleasure and thank you for having me come on today
and talk about this.
Carolyn:
Thank you too, Wendy. Do you have any other comments?
Wendy:
No, but congratulations on your publication, Andrea.
Andrea:
Oh, thank you so much, Wendy. I was really happy to get the message
that guys were excited about it. Thank you so much.
Carolyn:
You’ve been listening to Circulation on the Run. Thank you for
joining us this week and please tune in next week.