Circulation February 20, 2018 Issue

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Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and it's editors. I'm Dr. Carolyn Lam, Associate Editor from the National Heart Centre and Duke National University of Singapore. This week’s issue is the Go Red for Women issue, my favorite discussions of the year happened during this podcast.

Today, I am so delighted to have with me, our Editor-in-Chief himself, Dr. Joe Hill, from UT Southwestern, as well as, of course, the editor that made this issue possible, Dr. Sharon Reimold, also from UT Southwestern. Joe, would you like to tell us a little bit about this year’s Go Red issue? From the birds eye view.

Dr. Joseph Hill: Well Carolyn, I share your enthusiasm. This is our second annual Go Red for Women issue and it is fantastic. It has generated great interest in the community. We had a number of papers coming in, unsolicited. Our frame of reference-type content. Original research articles. State of the art.

We clearly touched a nerve with this issue. As we will discuss further, we shine a bright light here on some of the very best science, focusing on sex-based differences in the biology of heart disease, the presentation of heart disease, how women function, and are treated in the academic environment. The ways in which they are impacted by psychological stress. It's an absolute bonanza of science, in this issue.

Dr. Carolyn Lam: You took the words out of my mouth. It is a bonanza issue. I mean, we had seven original articles. Lots of new stuff, but lots of good, important papers on plain old ischemic heart disease. What I really liked was that, three of these original papers focused on myocardial infractions, in the young, and their risk factors, prevention, and so on. Sharon, shall we go through those? I mean, there was the one on genetics, lifestyle, and LDL in young women.

Dr. Sharon Reimold: That would be great. That manuscript looked at, sort of, a distribution of lipids, in women, that would have otherwise expect to be healthy. They sorted them out by individuals that had extremely low LDL levels and those that had high LDL levels. They pointed out that the individuals with high LDL levels. Ended up having hypercholesterolemia heritable, but they also found genetic variance of related to those with low LDL levels. I think this manuscript points out the importance of screening younger women for lipid disorders and incorporating those data into their clinical management.

Dr. Carolyn Lam: Absolutely. Then, there was that paper that, again, talked about young women experiencing myocardial infarction, and the sex differences in their presentation, and perception. That was super cool. From the Virgo trial.

Dr. Sharon Reimold: There are several other papers, that are published, demonstrating that women tend to have multiple symptoms when they present with symptoms of ischemia. That's true for both myocardial infarction, as well as for other unstable syndromes. They certainly have more symptoms than men.

But what was very interesting about this particular paper, is that when women presented with multiple symptoms, providers were less likely to think that the symptoms were due to a cardiac etiology. So even when women are trying to tell their providers what is going on, sometimes, they're not taken seriously, because they have multiple symptoms. So I'm hoping that this resonates with our providers, clinical providers, and we think about this. Whether we're cardiologist, or emergency room providers, or even EMTs.

Dr. Carolyn Lam: Exactly. Then, the third original paper in these young women, kind of scary, mental stress induced myocardial ischemia.

Dr. Sharon Reimold: Right. So there's been a lot of interest in the myocardial infarction without obstructive coronary disease, in the last year or two. Because a lot of those individuals, even thought, they don't have typical atherosclerotic pathologies, they don't have good outcomes. So this article looks at the role that mental stress plays in inducing ischemia, by EKG, in these individuals.

I think we still need to understand more about how this contributes to the biology, and outcomes, in these individuals. Also, get a better understanding if this is also true in older women, who have ischemic heart disease.

Dr. Carolyn Lam: Exactly. You know, but speaking of the older women, it's not like the issue left out the older women this time either. I did think that the study on the metabolic predictors of incident ischemic events, in postmenopausal women, was really interesting, as well. Basically, the authors identified a cluster of novel metabolites, that were related to oxidative stress, that added to. you know?

They weren't correlated with the traditional biomarkers. Really suggesting that there may be a whole area of metabolites, and other biomarkers, that we may be needing to check, and to understand better, for risk prediction. At least, in older women. But, of course, in men as well. Then, finally, there was the data on sex differences from the STICH trial, on surgical revascularization. What did you think of that one?

Dr. Sharon Reimold: Well, I thought that this was a very important addition to the cardiology literature. Because we are accustomed to thinking of women as having poor outcomes, after they have cabbage revascularization surgery. Certainly, the STICH trial enrolled patients who were more sick than the average patient, with their underline LV dysfunction. They found that sex did not influence the outcomes in this trial.

So the importance of that, for the medical community, is obviously we should not consider sex as a barrier to sending women to surgery, even if they're at high risk, because they can have equally good outcomes.

Dr. Carolyn Lam: Exactly. Important message. Important paper. Then, moving from ischemic heart disease. We also had a paper focusing on stroke, which I thought was a really intriguing one, talking about atrial fibrillation, and questioning if being a woman is a risk modifier, or a risk factor. Do you want to elaborate on that one?

Dr. Sharon Reimold: So instead of the using the CHA2DS2–VASc algorithm they use the CHADS2-VA program and then looked to see how well that predicted risk, and how much the S and C, the gender actually influenced outcome. I think this is an important issue. I'll say it's for women, perhaps. because as a woman, you know, without doing anything, you start out with a risk factor of one. Then, once you get to a certain age you have a risk factor of two. That's even for somebody who has no other disease processes.

Dr. Carolyn Lam: Yeah.

Dr. Sharon Reimold: So I think it's a little different way to look at how the risk is modified. They propose that if your CHADS2-VA score is two, or greater, certainly, your risk goes up if you're also female. They propose, then, that you would treat those patients more intensively. It's just a little twist on the CHA2DS2–VASc and maybe will provide us different ways to refine our knowledge about outcomes in atrial fibrillation.

Dr. Carolyn Lam: Yeah. I love that paper, too, because it's quite different from the papers that we had in the first Go Red issue. Isn't it? But in the first Go Red issue, we had lots of papers on pregnancy. The current issue certainly has those papers as well.

Dr. Sharon Reimold: Yes. There are increasing number of pregnancy related complications. Both maternal, and offspring, complications that predict increased cardiac risk, down the line. This issue has a series of women who had, had preeclampsia during pregnancy, and found that 17% of their women had a coronary artery calcium score of greater than 95th percentile. While that doesn't entirely get you from the biology, in between those two, it at least gives you an idea of where to start going back, and taking a look at what's going on.

Dr. Carolyn Lam: What about the one in rheumatic mitral valve disease? Pregnancy outcomes in women with those?

Dr. Sharon Reimold: So rheumatic heart disease and pregnancy outcomes, you know, we don't see much written about it anymore. because most of the active disease is in certain areas, in the world. But obviously, these women can have symptoms related to their mitral stenosis and/or their regurgitation during their pregnancy, with heart failure being the most common presenting cardiovascular complication. While some of that is much more quantitative, than perhaps, it was in the past, which is useful.

I think that the take-home message from this particular trial is that you need to talk to these patients, and screen them, prior to pregnancy, if possible, to help achieve the best possible outcome. I think that the risk of heart failure was a little bit less than 2% during the trial, which is obviously much higher than the average woman's cardiovascular risk during pregnancy.

Dr. Carolyn Lam: this is still definitely an important issue, in many other parts of the world. I really appreciate that you invited this editorial, that gave that global perspective. The editorial, by Athena Poppas and Katharine French, really beautiful work there. You know, I have to say that one of my favorite papers, in this issue, was that in depth paper, regarding gender versus sex, as a social determinant of cardiovascular risk. I found that so intriguing, the first time I read it, and just love it.

Dr. Sharon Reimold: Social determinants of health is a hot topic, in a lot of different areas of medicine these days. But they point out some really interesting things, that I don't think I had thought about. One is the fact that, when you are a child, you know maybe 10 or 12, that boys are encouraged more to be physically active. Athletics and other sorts of activities. Whereas many girls, don't have the opportunity or are not as interested. Perhaps we set up an abnormal social situation very early in most people's lives.

Dr. Carolyn Lam: Yeah, that represents cardiovascular risk. I know. That stuck out to me too.

Dr. Sharon Reimold: Obviously, how and where people live, as children, can influence outcome. That can be influential for both boys and girls. But I think bringing the idea back to cardiovascular diseases, and risk, are really long term, lifelong processes, that we can make changes in, from a preventative standpoint, even in young people.

Dr. Carolyn Lam: Something we don't usually think about and I just love the way it was presented, so clearly, and I just love it. Now, to an area that really cuts close to the heart. Pun intended. That is the bias in research grants, bias in manuscript authorship. Joe you mentioned that, right from the introduction, I would love your comments on those papers.

Dr. Joseph Hill: The reality, that we all are aware of, is, in many countries, including the United States, 50% of medical students now are female. But as we move through the ranks, into the different subspecialties, and up the career ladder of academic cardiology, we see a thinning of female representation. Arguably, it's been improving, over the last number of years.

But the reality is, that there remains a bias against representation of women, in terms of extra mural grant funding, authorship on high-profile papers. This article digs into that, and analyzes those numbers, takes a snapshot of what it looks like at the present time. In some ways, I believe it's a call to arms on how we must do a better job of recognizing this and rectifying it, going forward.

Dr. Carolyn Lam: Sharon, did you have comments to add?

Dr. Sharon Reimold: Yeah. I mean, I think, I wholeheartedly agree with Joe about those sorts of things. I mean, we see the same types of issues in clinical cardiology as well as in the research components of what we do. we need to figure out how to do this better, so that we all can be productive, going forward.

Dr. Carolyn Lam: You know it's just such a beautiful issue. So rich, in so many ways. Was there anything else you might want to highlight to our listeners?

Dr. Joseph Hill: I might add that Sharon and I kicked off the issue with a brief introduction. Pointing out that the reality is, that one and four women will die of heart disease. Most women don't know that. Most healthcare providers don't know that. Many Cardiologist don't know that.

When you compare that to the realities of breast cancer, it's 1 in 40. It's 10 times different. Now, that community has done a fantastic job. The Susan G. Komen program, in the United States. The pink ribbons, that we see all around the world. That community has done a fabulous job of getting the message out about that grievous disorder.

We have to do better. We have to do better educating ourselves, educating the lay public, about the realities of heart disease in women. 1 in 4, around the world. We also have to do a better job of digging into the science. That's where this issue does an especially good job.

That the reality is that heart disease is different in men and women. It presents differently. It presents at a different age. The way in which women respond to therapies, can differ from men. So there's work to be done, in terms of awareness. There's work to be done, in terms of the underline biology. This is an especially exciting time in this arena.

Dr. Carolyn Lam: I couldn't agree more. I'd add to it, even sex differences and the perceptions about own symptoms, and that of women versus men with chest pain. Then, the whole gender, social element to it. Oh, just so much to discuss, so much to learn from.

Well, listeners you heard it right here. I want you to please send this episode, share it with as many other women as you can think of. Do help us to spread this message, it's such an important one.

Thank you so much, Joe and Sharon, for joining me today. Thank you, listeners, as well. Tune in again next week.

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