Circulation February 15, 2022 Issue

This week's episode is special: Circulation is proud to
present the 6th annual Go Red for Women issue podcast. Please
join Sana Al-Khatib and James de Lemos as they welcome authors
Michelle Albert and Sadiya Khan as they discuss their articles
"Shining a Light on the Superwoman Schema and Maternal Health"
and "Geographic Differences in Prepregnancy Cardiometabolic
Health in the United States, 2016 Through 2019." Then Sana
presents an overview of the other exciting articles in this
important issue.


Dr. Sana
Al-Khatib:         


Hello, and welcome to this special Circulation on the Run
podcast, focused on the sixth Go Red For Women issue of the
journal. I am Dr. Sana Al-Khatib. I'm an electrophysiologist at
Duke University Medical Center and a senior associate editor for
Circulation. I have the pleasure of co-leading the sixth Go Red
for Women issue with, my friend and colleague Dr. Biykem Bozkurt.
Very excited to introduce Dr. James de Lemos, the executive
editor for Circulation, who will co-host this part of the podcast
with me. Welcome, James.


Dr. James de Lemos:     


Well, Thanks. I'm delighted to be here.


Dr. Sana
Al-Khatib:         


The theme of our podcast today is social determinants of health.
We will discuss a perspective article in the issue, titled The
Interplay of Sex with Social Determinants of Health in
Cardiovascular Diseases, led by Dr. Michelle Albert, who is a
cardiologist at the University of California in San Francisco. We
will also discuss a research letter on geographic disparities in
pre-pregnancy cardiometabolic health in the United States from
2016 to 2019, led by Dr. Sadiya Khan, a cardiologist at
Northwestern Medicine in Chicago. Welcome, Doctors Albert and
Khan.


Dr. Michelle Albert:       


So pleased to be here. An honor to be part of the Go Red issue.


Dr. Sadiya
Khan:             


Thank you for having us.


Dr. Sana
Al-Khatib:         


Wonderful. So we'll start with the discussion and turn it over to
you, Dr. de Lemos, to ask the first question.


Dr. James de Lemos:     


Well, thanks, Sana. Michelle, let's start with you. I love the
title of your essay. I'd like you to sort of orient our listeners
as to why this title, why the topic and what you write about in
your piece.


Dr. Michelle Albert:       


Thank you, James. The title of the essay or Perspective is
“Shining a Light on the Superwoman Schema and Maternal Health.”
We felt, along my coauthors, Dr. Rachel Bond and Dr. Annette
Ansong--Dr. Ansong is a pediatrician, actually. Dr. Bond is also
a cardiologist. We felt that it was really important to put
forward the psychological parts of the maternal health crisis as
a major social determinant of health. Most often, the focus is
only on the other risk factors that we know of, like
hypertension, diabetes and obesity. And while those are also
extremely important, it is actually the interplay between those
risk factors and social factors, including racism, including
access to care, that actually drive the maternal health crisis
for women of color. Particularly for black women, who have about
three to four times the mortality and pregnancy complications,
compared to white women.


Dr. James de Lemos:     


Michelle, one thing that you've really defined your career by is
moving to the biology of adversity. I thought the figure in your
paper was striking. Can you expand a little bit on what you mean
by this, and how these social determinants and the pernicious
effects of things like racism and psychological stress, translate
into the biology that I think Sadiya will tell us about, even in
her research letter?


Dr. Michelle Albert:       


Yes, James. As you know, I've had a longstanding research history
and portfolio, looking at the interplay between biology and
social factors, coined the biology of adversity. The adversity
part of this is something, we often think about the ACEs, adverse
childhood experiences, and think about how those relate to health
outcomes, including cardiometabolic and cardiovascular health
outcomes. But as we think about adults, actually, it's the adult
environment that actually defines adversity for children.
Certainly, as it pertains to black women and other women of
color, there are certain special circumstances that get embedded
into the whole framework of the biology of adversity, that lead
to poor overall cardiovascular outcomes, but also maternal and
non-maternal health outcomes. So conceptually speaking, the
framework of the biology of adversity is the incorporation of
stressors into the brain. That then results in a hyper
inflammatory milieu, combined with dysregulation of the
hypothalamic pituitary access, as well as the flight or fright
hormones or the up-regulation of the sympathetic nervous system.
And actually importantly, the down-regulation of the
parasympathetic nervous system, which is an area that is actively
under research currently, that then results in the downstream
cascade of health effects. For black women, this is characterized
by, in part, the Superwoman Schema, which includes several major
themes. The first major theme is the history of oppression and
racism and sexism. Also, a history of disappointment, the
influences of spiritual values and form other influences,
interplayed. These are stressors that incorporate with other
stressors. And then there's an interplay with subscales, that
focus on the ability to succeed, despite limited resources.
Putting others ahead of yourself. So less self-care for yourself,
but putting self-care of others ahead of your self-care, the lack
of showing vulnerability, as well as suppressing one's emotions.
So, all of these things interact with behavior and genetics, as
well as epigenetics, to flow into that cascade of the biology of
adversity. For me, I gave this presentation four years ago now,
at American Heart Association, where I sort of reformatted this
whole biology of adversity to incorporate the Superwoman Schema,
which was first defined or characterized by Cheryl
Woods-Giscombé, who is a PhD scientist in the United States.


Dr. Sana
Al-Khatib:         


Now, that was very helpful and insightful, Michelle. Could you
tell us about, what are the main next steps that need to be done
in this area, that you think are going to be important to move
this line of research forward, so that we can actually change
this situation and really improve healthcare for these women?


Dr. Michelle Albert:       


Well, I like to think of the answers to that question on several
levels. So, I think one of the first levels is ensuring that
women, especially women of color and specifically black women,
are aware of the fact that hypertension, preeclampsia and
eclampsia are risk factors, not only for their pregnancy, but
also for cardiovascular disease later on, and for their children
developing hypertension and cardiovascular disease later on. So,
I think education is really important, on one level. On the next
level is, actually having a continuum of care, where women are
asked to get early prenatal care, even when they're contemplating
pregnancy. So that they can be screened for hypertension,
diabetes and their stressors, assessed and put in contact with
resources. Having doulas, midwives involved in this process, as
well as cardiologists who are involved in the pregnancy setting,
as well as post-pregnancy for these women. Then, there's an
advocacy initiative that has to take place, that focuses on
getting aid. Kamala Harris has put forward a bill to actually do
just that for maternal health, focusing on racism and bias in
healthcare, because black women across the spectrum of
socioeconomic status, experience poor maternal health outcomes.
So, this is not only an access to care issue. It's not only a
socioeconomic status issue. It is an issue that pertains to the
women not being listened to, with racism and other stressors. I
can't stress those first two things more, the whole
discrimination part of it, and dumbing down the concerns of black
women. Then, I think on a research perspective, certainly the
American Heart Association has got now this HERN Network, which
is a network that's going to focus on research around maternal
health. So in that context, figuring out the best care models for
women. Understanding the biology and how it interplays with poor
outcomes later on, is also very important. One point around the
biology that I want to point out for, let's say, African American
women and actually Asian women as well, is that there's a higher
prevalence of fibroids. There's very little research focusing on
fibroids and its importance on maternal health outcomes and even
the care for those women. Frankly, in my mind, a lot of that has
to do with bias and how we value the healthcare of certain groups
of women over other groups of women. So, those are some of the
things, in terms of the solutions.


Dr. Sana
Al-Khatib:         


Absolutely. Before we move on to the presentation by Dr. Khan,
are there any final words Michelle, that you'd like to share with
the group, in terms of any final wisdom, so to speak, that you
want to leave the listeners with?


Dr. Michelle Albert:       


Yeah. I would just say that the maternal health crisis is
preventable and it is tied into... Much of our audience are going
to be healthcare providers. To the healthcare providers, I'm
going to say, you really, really need to listen to these women
when they tell you that they're experiencing certain symptoms.
You also need to dig deeper to find out about their concerns,
especially their stressors, in addition to making sure their
blood pressure is controlled and that their weight is managed.


Dr. James de Lemos:     


Well, thank you, Michelle. We'll turn to Sadiya now, and her
team's research letter on geographic differences in pre-pregnancy
cardiometabolic health in the US. For our listeners, I think what
you'll see, if you read this paper, is how remarkable the
research letter format is, and how much information Dr. Kahn and
her team have conveyed in this really, really powerful letter,
that I think has major public health implications. Sadiya, do you
mind orienting our listeners to what you studied and how you did
it?


Dr. Sadiya
Khan:             


Thanks, James. And again, thank you for the opportunity to join
you guys in this podcast. I think Michelle very eloquently set up
the preface for this research letter, which was understanding
that health in pregnancy begins before conception. That was
really the reason we wanted to focus on health factors,
particularly cardiometabolic health factors, like body mass
index, diabetes status and hypertension status in the pregnant
individual, prior to pregnancy. The second piece of this that we
were really interested in, is that we had observed that there are
significant differences across the United States, in maternal
morbidity and mortality outcomes. There are much higher rates of
pregnancy-related deaths occurring in the South and Midwest,
compared with other states in the US. That led us to ask this
question, if we're able to better describe or define health prior
to pregnancy, will we see similar patterns? We used the Centers
for Disease Control Natality database, which includes all live
births in the United States. So, the strength of this dataset, is
that this is a surveillance system employed by the CDC, to
monitor and record health outcomes of the pregnant individual and
the newborn in the United States. Using this dataset, we were
able to display maps for pre-pregnancy cardiometabolic health and
look at changes from 2016 to 2019. Unfortunately, there's not
much positive news, in that we've seen continued declines in
favorable or optimal pre-pregnancy cardiometabolic health, which
we defined as having a normal BMI and the absence of diabetes or
hypertension. In addition, we saw that the levels of favorable
pre-pregnancy cardiometabolic health were lower in the South and
Midwest. It starts to set up some questions about upstream social
determinants of health, that may be playing an important role as
we start to address this problem at the individual level, but
also at the societal and population level.


Dr. Sana
Al-Khatib:         


Very interesting and important findings there, Sadiya. Are you
planning to work on additional research, to build on the research
that you were publishing in this issue?


Dr. Sadiya
Khan:             


One of the most important questions that came from this are, what
are the potential ways to start to address and support care for
pregnant individuals, or as I think is Michelle really nicely put
it, is for preconception care. So, thinking more about the
reproductive life course before pregnancy, as well as during and
after pregnancy. For that, one of the things that seems to be
potentially really important, could be how Medicaid expansion has
helped in states that have expanded, and differences between
states that have or have not expanded Medicaid. Knowing that,
that probably isn't sufficient, but it has that been helpful.


Dr. James de Lemos:     


Yeah. I was struck, Sadiya. I mean, Michelle's essay and your
research project really shine a bright and distressing light on
maternal health in the US, I think and the crisis that we're
under, that many of us don't even maybe recognize is happening.
The time trends you showed were, to me, striking, giving over
such a short period of time, how much maternal cardiovascular
health has declined. It seems, indirectly at least maybe, that
declining at a higher rate than overall cardiovascular health. I
first applaud you for writing on this topic because I think it
brings this issue to light, in terms of a public health crisis,
frankly. But I wonder if you have any thoughts on why
specifically, things are declining at such a higher rate for
pregnant women or pre-pregnant women, maybe relative to national
trends? Maybe they're not. Maybe this is what's happening across
all age and gender demographics.


Dr. Sadiya
Khan:             


It's a really important observation. I agree with you. It seems
like it's much more striking in this concentrated and focused
group of individuals, that are pregnant and giving birth. It's
possible because of the age range that we focus on, the 20 to 44
year old age range, that there are potentially more significant
declines happening during this time period. We know
cardiovascular health in general, appears to have some
age-dependent dips, generally around adolescence. That early
adulthood, college age period seems to be where a lot of
cardiovascular health decline happens. So, I think that's what
we're observing, as we're seeing these more striking trends in
this age group. But it would be interesting to know, compared to
non-pregnant individuals and across the life course, if that is
in fact, the case.


Dr. Sana
Al-Khatib:         


Then I'll ask you what I asked Michelle, Sadiya. Any final words
of wisdom that you'd like to share with our listeners?


Dr. Sadiya
Khan:             


I don't know if I'll be able to speak as eloquently as Michelle
did. I think her responses really capture both of these papers
and thinking about ways forward, about how we can dress the
maternal health crisis. But I think that the word that she used,
that really sticks with me and is one of the reasons that I'm so
passionate about this work, is that this is preventable. That
there are so many different things that could be in place,
whether it's at the individual clinician and patient level, at
the individual health system level, at the state level, as we
looked at here, but really at the national level as well. I think
we have a lot of work to do, but there's a lot of things that we
know can help.


Dr. Sana
Al-Khatib:         


Great. Wonderful. James, any final words from you before we wrap
up this part of the podcast?


Dr. James de Lemos:     


First, Sana and the rest of the Circulation team, I congratulate
you on another spectacular Go Red issue, that really is such an
important endeavor. You and Biykem have done an incredible job
leading this. I thank Michelle and Sadiya for coming on today,
but also for their work. I think raises the stakes here, that
we've got a public health crisis affecting women, and
disproportionately affecting black women in the United States.
It's underappreciated. I think you both point out that it's
preventable. So, I think it's a call to action. It's a really
well stated and an important topic.


Dr. Sana
Al-Khatib:         


Wonderful. Well, thank you so much, James and Sadiya and
Michelle. Thank you so much for submitting your excellent work to
us. Thank you for being with us today. This concludes this part
of the podcast. Thank you. Next, I'm excited to provide you with
a brief overview of the issue. We have two original articles. One
is on genes that escape X-chromosome inactivation, modulate sex
differences in valve myofibroblasts.   This one was
submitted to us by Dr. Kristi Anseth and her team. The study
elucidated sex dependencies in myofibroblasts activation pathways
and transcriptome analyses and small molecule interventions,
implicating genes that escape X-chromosome inactivation, in
regulating sex differences in the progression of aortic valve
stenosis. The authors highlight the importance of considering sex
as a biological variable, to understand molecular mechanisms
underlying aortic valve stenosis and help guide sex-based
precision therapies. The second original article is by Dr. Elena
Aikawa and her team. It is on Prothymosin Alpha, a novel
contributor to estradiol receptor alpha-mediated CD8+ T-cell
activation and recognition of collagen cross-reactive epitopes in
rheumatic heart valve disease. This paper provides novel findings
that will likely have clinical impact down the road. As the
authors pointed out, understanding the Prothymosin Alpha and
estrogen sensitivity mechanisms to control the CD8 T-cell
function may indeed provide insights into treatment for rheumatic
heart valve disease. In this issue, we have three research
letters. One letter was on the geographic disparities in
pre-pregnancy cardiometabolic health in the US. You just heard
about this paper in the first part of the podcast. Another
letter, by Dr. Pradeep Natarajan and his team, offers information
on the microvascular outcomes in women with a history of
hypertension in pregnancy. It highlights that hypertensive
disorders of pregnancy, especially preeclampsia, are
independently associated with reduced microvascular indices. The
investigators called for further research, to translate these
findings into cardiovascular risk reduction strategies for women
with these conditions. The third research letter, by Dr.
Androulakis and his team, provides insights from cardiac magnetic
resonance and angiography screening on spontaneous coronary
artery dissection, also known SCAD. Theirs was the largest cohort
of SCAD patients screened for peripheral vascular pathology by
magnetic resonance and geography, to date and one of the largest
to assess the SCAD-related impact size and relevant associations.
They concluded that cardiac magnetic resonance has valuable
contribution to the investigation of SCAD patients. In this
issue, we have six perspective papers. In addition to the
Perspective paper that you heard about from Dr. Michelle Albert,
there are five perspective articles that span topics of great
clinical and research relevance and importance. One perspective
article, led by Dr. Carolyn Lam, tackles incorporating sex and
gender into the design of cardiovascular clinical trials, a very
important topic. Dr. Lam highlights the importance of sex and
gender to the optimal interpretation, validation and
generalizability of cardiovascular clinical trial results.
Another perspective by Dr. Kathryn Lindley presents a call for
action to address increasing maternal cardiovascular mortality in
the US. This actually ties in with the initial part of the
podcast. Dr. Lindley offers insightful suggestions, regarding
strategies that could improve maternal cardiovascular care.
Another perspective by Dr. Anne Curtis, addresses sex differences
in response to rhythm management devices. Dr. Curtis reminds us
that the conclusion that should be drawn from the many studies
that have been conducted on cardiac rhythm management devices, is
that these devices are indeed effective in both men and women,
but they're still significantly underutilized in women eligible
for those therapies. Dr. Curtis calls on us to be ever vigilant,
to provide sex-neutral medical care to all patients, when
clinical trials don't provide a strong rationale to do otherwise.
I'm quoting her here. Another perspective paper by Doctors
Mauricio and Khera, addresses statin use in pregnancy. They raise
the of whether it is indeed time for a paradigm shift. This
article was prompted by the FDA's request to remove the pregnancy
Category X label for statins that was issued in July of 2021. The
authors encouraged clinicians to use shared decision making. They
add that those with atherosclerotic cardiovascular disease
events, especially recent ones, should be encouraged to continue
statins during pregnancy or resume them as soon as possible, if
they're withheld. For those with heterozygous familial
hypercholesterolemia, previously reasonable LDL control and no
manifest vascular disease, there may be more tolerance for statin
deferral during pregnancy, but they definitely highlight the need
for dedicated research in this area. The last perspective, led by
Doctors Okwuosa and Zaha tells clinicians what they should know
about sex differences in cardio-oncology. They highlight sex
differences in cancer and cancer treatment, cardiovascular
diseases and the intersection of these conditions, that are
likely to be quite helpful for clinicians taking care of such
patients. Don't forget to check out the Pathways to Discovery
section, where you will find a very interesting and motivating
dialogue between Dr. Maryjane Farr and Dr. Biykem Bozkurt in
which Dr. Bozkurt describes her career journey. I personally
enjoyed reading that interview and found it quite inspiring. In
closing, I want to express my deepest gratitude to my co-editor
Dr. Bozkurt, the Editor-in-Chief for Circulation, Dr. Joseph
Hill, the Executive Editor for Circulation, who was with us at
the beginning of the podcast, Dr. James de Lemos and all the
authors who submitted the research for this issue. I also want
wholeheartedly thank and acknowledge the Circulation Associate
Editors and Staff, who work tirelessly to enable us to produce an
excellent Go Red for Women issue. I am very excited about this
issue and hope that you will like it as much as I do. This
concludes our Go Red for Women issue, Circulation on the Run
podcast. Thank you for listening.


Dr. Greg
Hundley:          


This program is copyright of the American Heart Association 2022.
The opinions expressed by speakers in this podcast are their own,
and not necessarily those of the editors or of the American Heart
Association. For more, please visit ahajournals.org.