To Improve Cardiac Outcomes for Women, Increase Their Representation

JOEL BERVELL: Right now in the United States, 44 percent of women live with some form of heart disease. It’s the number one cause of death among women. And these numbers have been steadily climbing since 2010, up now by nearly a third. Yet, over the past 20 years, the number of women entering cardiac medicine specialties has grown by only 1 percent. Currently, about 15 percent of the cardiologists in the United States are women. And that slow gain can actually be linked to the pervasiveness of heart disease among women. Why? There’s a lot of reasons that we’ll dive into.

My guest, Dr. Martha Gulati, is a cardiologist at the Cedars-Sinai Heart Institute in Los Angeles, where she serves as associate director of the Barbra Streisand Women’s Heart Center. Dr. Gulati is also president of the American Society for Preventive Cardiology. She’s here to talk with me about what that gap means to patients and women everywhere. We’ll talk about clinical trials, the standard of care treatment today, and what’s on the horizon for women in heart health.

Dr. Gulati, thank you so much for joining with me.

MARTHA GULATI: Oh, thank you for having me.

JOEL BERVELL: So I’ll jump right in. As an international leader in cardiac medicine, you’re a part of a small group of women in the field. As I mentioned, in the United States, only 14 percent of cardiologists identify as women. I want to talk to you about that reality in this specialty. But first, I also want to talk specifically about how that small number of women in the field impacts what we know about women’s cardiac health. The inclusion of women in cardiac clinical trials is related to the number of female cardiac doctors. Can you explain why there’s that direct correlation between those two data points?

MARTHA GULATI: Yeah, you would think it wouldn’t matter, right? You’d think that we’d care about the number one killer of both men and women equally and understand that women and men are not the same. But I think that there has been an exclusion of women in cardiovascular disease trials clearly for so many years for so many reasons. But one of the main contributing factors has been as cardiology, as you already said, has been very male-focused in the sense that most of practicing cardiologists were men. And they didn’t seem to think about the issues that were unique for women that needed to be considered when we were studying anything.

We know there’s differences. Simple example is that women are more likely to bleed after we give certain blood thinners in cardiology. We know that. But yet, do we ever consider that when we’re studying these drugs that we should figure out is it metabolized differently in women? Is it the dose because women tend to be smaller? What is it that’s making women have these issues? But somehow, the movement to studying women started by women cardiologists because we were realizing we’re ignoring 52 percent of the population.

And there is some historical reasons too for this. If you look at why women specifically were excluded from trials, you can go back to the 1960s. And where we can start the story is that thalidomide was a drug being used in Europe to reduce morning sickness in women. Unfortunately, it had this terrible side effect that affected the offspring. And as a result, almost the next year after all of this was seen in the United States, they immediately, the FDA said, “We’re going to exclude women of childbearing potential.” So because of that ruling — which I understand the importance of it and why they did it — but maybe it got translated to go beyond that.

It actually started, as a result of that, excluding women in pretty much all trials. So in the ‘80s, the NIH did make some recommendations to include women in studies, but nothing really happened significantly from that statement. In the 1990s, we finally had a woman heading up the NIH [the National Institutes of Health], a woman cardiologist, a very famous woman that is one of my heroes, Dr. Bernadine Healy. And so she actually was the woman who established the Office of Women’s Health Research at the NIH. She also helped make the movement that Congress mandated the inclusion of women in trials. And finally, the FDA removed those restrictions of participation of women of childbearing potential.

Now, that’s also the time that the study called the Women’s Health Initiative started, telling us that hormone replacement therapy may not be the fountain of youth that everyone thought it would be. Now, all those steps were good, but it still didn’t hold anyone accountable. It didn’t force anyone to get more women in trial. So then in the 2000s, the FDA said, “Well, we don’t know a lot about women who are pregnant, who get drugs by accident or don’t know that they’re pregnant, at least that would be a way for us to understand what’s happening if you get exposed to those drugs because nobody’s going to do trials on them.” So they did start this exposure registry for pregnant women, so we got some information.

And then in 2010, for that decade, the FDA said, “Well, medical devices aren’t really being studied in women. They’re coming up for, come for patents. They don’t tell us anything about how they worked in women.” So it’s not until 2020, or really 2022, where the FDA finally said that sex and gender and devices need to be reported. The Institute of Medicine put out a report in 2022 as well about inclusion of women in trials.

That’s where we’re at. And still, I would argue to you that despite us being in a modern era, we still don’t have a way to hold people accountable. Meaning, when pharmaceutical studies do trials or NIH does trials, they might want to include 50 percent women or whatever the appropriate population prevalence should be included. But if they’re rushing to get their trial done, they don’t say to the investigators, “Now, the rest of the people need to be women.” We need to change that. So we should just recognize we’re in a modern era, but in cardiology, we’re still thinking about men more than we are about women.

JOEL BERVELL: Absolutely. And I’m so happy that you really drew that line between history to where we are today because it shows how far we have really come, right? You’re talking about how it’s just 2022 that we finally got this report saying, “Maybe yes, in the ‘80s we talked about it a little bit, but it’s still an issue. We’re still not doing a good enough job.” I mean, it really goes to show that medicine is a slow-moving field. I’m also curious about kind of the historical low rates of inclusion of women of color. That’s another issue. Can you talk a little bit about that lack of inclusion and what the data says in terms of clinical care and outcomes specifically for women of color?

MARTHA GULATI: We do not have much diversity in our trials; at least we collect it. And we do have an improvement in getting Black people into our studies. Again, the way that we should be looking at inclusion is who’s suffering from the disease and based on the population prevalence, do we have an appropriate representation? So meaning, if we’re doing a study on hypertension, for example, we know Black people have higher rates of hypertension, they should be overrepresented in such a trial. So we need to start thinking about studies differently because I do think the exact same issues exist in these problems that I pilot about women. And in fact, we wrote a paper actually outlining how to improve diversity of participants in cardiovascular trials. We need to understand how drugs work, how procedures work, how transplants work, and also the barriers to treatment that exist in people of diverse backgrounds. all these issues matter.

And like you started saying, There’s not many women in cardiology. Guess what? There’s not a lot of diversity in cardiology. We’re trying to improve that on both counts. The American College of Cardiology now has a diversity and inclusion committee. And we’ve started thinking about how we grow the future of cardiology. What do we want cardiology to look like one day? And I hope that we want it to look like the population that we serve. And for some of us, I think we take the idea that we need to grow the population as young as possible. We’ve gone into the community often in high schools, into groups that might not have the luxury of knowing a neighbor or knowing a family member who’s in medicine, and being able to open that door to them and help them create a exposure to cardiology or to medicine so that they think about this as a future career. Because even when they’re in residency may be too late if the medical school population is also not diverse enough for us.

JOEL BERVELL: Absolutely. Yeah. I think about that whole pathway of getting into medicine, and even in my own experience, that was exactly how it worked for me. I was fortunate enough to grow up in the Seattle, Washington, area where there was so many incredible pipeline programs that were committed to getting kids as young as possible into programs so that 10 years, 20 years down the line, we’re thinking about things like this, we’re thinking about why is there no diversity, and we’re starting at a young age to actually make these differences.

Beyond the profession, there’s also been an enormous amount of public awareness campaigns that have happened in marketing over the past few years calling attention to the lack of research in specialized care. You mentioned a little bit about some of the metrics that you would use like prevalence and looking at that, but what are some metrics that you and your colleagues would use to measure impact on patient education?

MARTHA GULATI: Yeah, that’s a good question. I guess the problem is, we don’t actually have any real metrics to say how effective things are for our patients. And I do think more and more hospitals are taking the patient’s voice and including the community in things that they’re doing in terms of their outreach, in terms of understanding how they can improve health of their community. Again, use something like hypertension as an example. First of all, you need to know when we make recommendations as physicians, check your blood pressure at home, for example. Well, again, that makes the assumption that everyone can afford to get a blood pressure cuff. And even if they’re $70 to $150 or maybe even more expensive if you want a fancier one, but that amount of money is not what many people will say that they can afford to do. There’s a lot of variables that affect somebody who’s of privilege versus somebody who is not.

And I’m a preventive cardiologist, and so we can do a lot of procedures in the hospital, take care of people in different ways, our technology has never gotten better. When you’re sick, we can take care of you. But we are sick care, we’re not health care. If we really want to invest in prevention, which I think is the most important thing, we really need to be talking about these issues where people can be empowered at home to really know what to do and to also be able to take care of their health. I think there’s so much to be done, but I think to your question about what metrics we have, I don’t know that we have them yet.

JOEL BERVELL: Mm-hmm. And I really did like that last point you were making as well, just the importance of health literacy and how unfortunately in the United States, we aren’t very health literate. And I guess I’m now even going down this kind of medicine talk so I want to continue there. But what are some other significant gender differences that require standalone inquiries?

MARTHA GULATI: So gender and sex are obviously two different things, and both are important, but let’s just define them. Gender is a social construct and it’s how you’re seen by society. So whether you’re seen as a man, or a woman, or you’re seen as trans, the way that you’re viewed by society, affects your access to care, it affects your employment, it affects your lifestyle, it affects where you live, it affects your financial conditions, and whether you can access certain medication. So that’s very important, to understand somebody’s gender.

Now, biology is sex, meaning if your genetic chromosome makeup is XX, that’s biologically female, and of course XY means biologically male. So the reason that’s important is that every cell in the body has a sex, and therefore every gene and molecule in your body is influenced by your biological sex. So if drugs are metabolized, for example, differently, that’s important for us to know, if they respond differently to some therapy that we’re doing, or our recommendations for blood pressure, for example, or even exercise differ by sex, it might be. But if we’ve never asked those questions, we’re going to continue to say, “Oh, everything’s the same. Do the same amount of exercise that we tell men to do, blood pressure the same.”

Why do we think they’re the same? This, to me, bothered me so much that it ended up being my first project. I saw what our recommendations for fitness were. We had this fitness equation that’s for men and women, and it was the same equation. I was like, “How can that be the same?” And we came up with an equation for women which was different for men. And so I mean, again, biologically, there’s things that differ and we need to understand that. And of course for women, hormones and pregnancy affect cardiovascular risk and affect other things as well. So biology matters. So sex matters, gender matters, and there’s so many questions that I personally have and that I think our community has that still are left to be answered.

I think something that’s very timely and really important in the U.S. population right now is the influence of pregnancy on cardiovascular disease, but also the relationship with maternal mortality. But then in the long term, the risk in the future for heart disease can also be found through pregnancy, meaning women who have preeclampsia or any type of hypertension during pregnancy, or have gestational diabetes, or preterm birth, or small for gestational age child. Those are people that tell us, just based on that stress test that we call pregnancy, that they’re at risk for heart disease in the future. These are the young women that have the risk of having premature heart disease and these are the people we should be investing more of our preventive efforts early on.

The question I would pose to you is really, should they be? There is some data of one of my colleagues here at Cedars published this data a few years ago in JAMA. And looking at blood pressure, women start out lower at the beginning of life, so why are the same numbers the same? And what she found is that actually, over a lifetime for women, the trajectory or the slope of increase, although blood pressure increases for both men and women as we age, that slope actually goes higher for women than men. And so the thought that that work at least gave to me is that maybe there’s a sex-based threshold for women that should be lower for women than men. We don’t have that data, I’m just hypothesizing here that why would we think they have to be the same?

And the problem is, again, we do all these studies predominantly in men, so we don’t always have these answers. Even if you look at cardiovascular disease, when we see it, when people have heart attacks as an easy example, we don’t always see obstructive coronary disease in women. But yet they had a heart attack. So maybe the pattern of a myocardial infarction is different in women or the pattern of atherosclerosis is different in women. And we do a lot of work here at my hospital related to INOCA, which is ischemia with no obstructive coronary artery disease, and MINOCA, which is myocardial infarction with no obstructive coronary artery disease. And these are diseases that we see much more frequently in women than in men, although they do happen in men as well.

And that’s an area that had been completely ignored until this really, this last decade where now we’re seeing a change where people aren’t just sending these patients home and saying, “False positive, just because you had crushing chest pain and your enzymes went up. Nothing to do here, folks.” Now, we’re seeing responses very different than that. And that’s a good thing. But we still, again, we don’t know the ideal treatment yet, we’ve got to figure that out. And that’s a lot of the work that goes on here at Cedars-Sinai.

JOEL BERVELL: Absolutely. I’ve been nodding furiously because there’s just so many gems in what you’re saying, of things that we could be doing or studies we could be doing. You talked about whether it’s the threshold for hypertension to understanding why it’s important to have these diversities in clinical trials, it’s literally so we can better serve and understand what diseases do people have and how does that vary based on sex and gender, et cetera. And it just reminds me of the first time I heard that MIs can look differently in men and women, that women sometimes come in with nausea and vomiting and maybe they have that crushing chest pain or they don’t, or that it radiates to the back instead of somewhere else. And that there’s all these different types of ways to understand it, but once again, we don’t do the studies and researchers that are out there looking at it. But also that there’s just so much more to explore in order to increase health overall.

MARTHA GULATI: I think that another thing, if I could add though, we also need to understand better is why we treat women differently than men and similarly why we treat people of different races differently than Caucasians or white people. When we look at women specifically in terms of the utilization of certain therapies, we know that there’s a bias in health care, meaning we’ll give drugs after a heart attack, for example, the lifesaving standard of care as we call it, guideline directed medical therapy. We give that more frequently to men than we do women. And then again, there is the racial differences as well. Well, why? I mean, again, these are lifesaving medications. The person has clearly, we know they’ve had a heart attack, they’re sitting in front of you. Why is there a bias in our care? Why will we be less likely to take a woman having a heart attack to the cath lab to open up her artery than a man? Why? I don’t understand that.

But yet, we see this data continue to trend in the United States and actually globally where we underutilize lifesaving therapy in women compared to men. And we can use a heart attack as an example. But we can also use other things like atrial fibrillation, which is pretty common. We’re less likely to anticoagulate women. I don’t know why. Are we worried about bleeding? I mean, if we are, then we have scores that help us determine who’s going to bleed more versus who’s going to have a stroke more, which one do you care about and then you do shared decision-making with the patient to try to determine which one they’re concerned about. We’re also more likely to offer a man compared to a woman to get them back into the normal rhythm after they have atrial fibrillation or offer them a procedure like ablation where we can get rid of it potentially for good.

We do these fancy procedures in cardiology called TAVR, which is where we replace the aortic valve without open heart surgery. Guess what? The amazing thing about TAVR was that when the trials went on, we actually saw women did better than men getting TAVR. And then now in practice, we see women are less likely to be referred for TAVR, less likely to be told that this therapy could be used even though they actually have better outcomes than men. Similarly, heart transplants, women are only a quarter of the heart transplants in the United States. I know there’s a lot of reasons why, but again, are we even offering women the same therapy? Because this is something where only implementation science will help us know how can we improve this, how do we improve outcomes, how do we improve the bias that exists in medicine where we don’t do something that we know is effective and we have at our hands? Why do we refer less women to cardiac rehab?

JOEL BERVELL: Yeah, and I think those are all such necessary questions that need to be asked. I do also want to ask about the role of mental stress in cardiovascular disease because there has been some research in that it is different and very real. What’s the latest research on that, and what are the next questions that should be asked about mental stress relating to cardiovascular disease?

MARTHA GULATI: Yeah, so there’s definitely a connection between the heart and the brain. But that connection happens more in women than it does in men. And so there is this thought that, again, that mental stress affects hearts first of all, of course, but might affect biological sex differently. And I think that that area we’re still trying to get more information, but there’s definitely a clear connection that our brains are connected to our hearts.

JOEL BERVELL: And what are stressors that can be addressed or reduced?

MARTHA GULATI: Well, the biggest one I think that can be or should be addressed is depression. Because I think that depression, we certainly know after you have been diagnosed with cardiovascular disease that patients who have had a heart attack or have had a bypass who have depression have worse outcomes. And so, I think one of the unfortunate things is that we don’t assess for depression that effectively in our clinical settings. We need to do more about that because we have medications and interventions, lifestyle interventions that can address depression effectively and treat them. I think we just don’t always take the time. Our medical studies don’t spend a lot of time actually on the mental health of our patients. Anxiety is obviously clearly connected to cardiovascular disease as well. And again, we have effective treatments, it’s just whether they’re getting utilized and whether our patients are getting referred often enough. But all of those need to be addressed because if you aren’t addressing the mental health part of things, you’re not going to be successful to really treat our patients effectively.

JOEL BERVELL: Earlier, you described yourself as an early interventionist and you also referenced HRT and the Women’s Health Initiative. What does it mean to you to be an early interventionist and why have you chosen to focus there?

MARTHA GULATI: Yeah, really what I mean is I’m a preventive cardiologist who tries to keep you from needing more of the health care system, needing interventions because I want you to live a life that’s healthy and free of heart disease if possible. Because I do think that it’s profound what an impact you can have on people by detecting early disease and changing the trajectory. We used to say this all the time in cardiology: 80 percent of heart disease is preventable. Well, it still remains the number one killer and it kills a lot of people. If anything in the last decade, we’re seeing a rise, we’re losing ground actually in deaths due to cardiovascular disease. Right now, the focus within the U.S. health system though is really rewarding interventionalists, meaning rewarding procedures, rewarding hospitalizations. I really think we need to change that. Instead of spending so much at the end of life or in hospitalizations, we should be putting more value on preserving health.

JOEL BERVELL: And in the beginning of our conversation, you mentioned hormone replacement therapy and how we used to think it was this lifesaving thing. How has that belief changed now? Actually, we don’t talk about this in medical school, so I’m very curious.

MARTHA GULATI: So there was a book written in the 1960s, I think it was, this book called Feminine Forever. So without any trials, without any data, people started saying that hormone replacement therapy was essentially the fountain of youth for women and could preserve their health, and their life, and their sex life, and their vitality if they took hormone replacement therapy. So hormone replacement therapy, until the Women’s Health Initiative results came out, was the number one prescription in the United States. And thankfully, Dr. Bernadine Healy asked for this trial to be done, marched on Capitol Hill, asking for the funding for a trial that will never be repeated, where all over the country, there was different sites and lots of diversity actually in these studies. And this helped us know what’s going on, but it also helped us answer the question, are hormone replacement therapy really going to reduce the risk of heart disease in people who don’t have heart disease?

Now, I know there’s a lot of criticism for the Women’s Health Initiative. But again, such a large trial. And this study overnight when the results were released, I remember this day distinctly, we showed that hormone replacement therapy actually did not reduce the risk of heart disease and may have increased the risk. It increased the risk of breast cancer. There were some benefits, obviously, in terms of fractures, but again, you have to know that it’s not preventing cardiovascular disease. Now, that dose of HRT is different than the current dose of HRT, agreed. And certainly, if you need it for symptoms, we’re not saying you can’t have it. It’s just whether you should be on it, should everyone be on it, we don’t have that data now. But it was overnight, changed how we approached women by doing a trial with women. I mean, literally that drug was no longer the number one prescription that day in July, if I remember correctly.

I mean, it just changed everything. Patients weren’t sure what they should do. And now, there’s conversations around people’s individual risk. Meaning if you’re at higher risk for heart disease or you already have heart disease, we don’t recommend hormone replacement therapy. If you’re lower risk and again, if your symptoms dictate it, it’s always a shared decision between the patient and their physician about what needs to be done in that current moment. But it really just showed us that one, women were willing to participate in trials, first of all, and that women deserve to be studied. We shouldn’t be just using drugs on them without actually studying them on them. I think that was the most dramatic thing of this study.

JOEL BERVELL: Wow, that’s so fascinating, I think, especially for a medical student to hear about in the moment. We didn’t always know that. And if this trial had never been done, who knows if we would’ve ever got in there.

MARTHA GULATI: I mean, that’s the thing. We should always look what is the evidence out there. Because if we haven’t got the trials on that, if we don’t have the randomized control trials on that, how do we know? Observational data will never answer everything for us. And that’s the problem, is we were reliant on prior observational data saying that this was beneficial. But again, observational data will always depend on who are you observing and why are they taking it. Are they more health literate? Are they somebody who has more financial means, greater education? All of these issues are important.

JOEL BERVELL: Mm-hmm. Well, Dr. Gulati, I appreciate you so much. I’ve learned so much personally. I know that listeners will be blown away. Thank you so much for being with me today.

MARTHA GULATI: It was my pleasure to be here.

JOEL BERVELL: Thanks for listening to this miniseries of The Dose on women’s health. If you haven’t listened to the series we did this spring on health equity, there are some great conversations in the feed. We’ll be back in the fall with more conversations, this time on health care costs and affordability.

This episode of The Dose was produced by Jody Becker, Mickey Capper, and Naomi Leibowitz. Special thanks to Barry Scholl for editing, Jen Wilson and Rose Wong for art and design, and Paul Frame for web support. Our theme music is “Arizona Moon” by Blue Dot Sessions. If you want to check us out online, visit thedose.show. There, you’ll be able to learn more about today’s episode and explore other resources. That’s it for The Dose. I’m Joel Bervell, and thank you for listening.