Women and Heart Disease: Is There Really a Sex Difference?

I am going to talk about the sex differences and specifically emphasize the things we’ve been finding out about women. Though I have no disclosures, I have no commercial interests. I think when we talk about women and cardiovascular disease, looking back historically is important. Looking at our trends and mortality is what really highlighted that there was something going on with women when we were seeing actually improvements in men, meaning less men dying from heart disease, as demonstrated on the blue lines here, which are the mortality curves for the United States. At the same time, when we were seeing dramatic reductions in mortality, in cardiovascular disease deaths in men, we were actually seeing an increase in mortality in women. And during about the 80s and 90s, what we started realizing is that we had excluded women from many of our studies and many of our trials, and we weren’t even applying our guidelines appropriately in women. Partially, that was probably because we didn’t include women necessarily in all the trials, and people were confused about whether even the the, the guidelines apply to women. Well, in 2001, we finally started seeing a reduction in mortality in women. And what happened in 2001? Well, some important things really did happen. It was the time that the Women’s Health Initiative was released. Additionally, that was the beginning of the Go Red Movement. And after the Go Red Movement started, there was a series of releases of guidelines specific to women in cardiovascular disease prevention that came out. And all of that probably contributed into the next decade of reduction in mortality. Now, what you’re seeing in 2014 onward, though, you can see a very dangerous trend actually occurring. We got to a point where there was less women dying from heart disease. But then in the last few years, we’ve noticed this increase in mortality in both men and women, which is a really concerning trend and something we really need to keep an eye on. It makes us question if the younger generation is not going to outlive its parents, as more and more risk factors become more and more prevalent in our society. And that’s actually true for both men and women. But when we talk about cardiovascular disease, as I said, women weren’t included in a lot of our trials, and we still have a lot of catching up to do. And in the late 90s Dr. Nanette Wenger said this. She said that we really took a bikini approach to a woman’s health. Well, she said the medical community is viewed women’s health with a bikini approach, looking essentially at the breasts and the reproductive system and almost ignoring the rest of the woman when we talk about women’s health. That was then. But still to this day, when you look at women’s health centers across the United States, you will notice that they still essentially focus on the reproductive systems of a woman or the breasts of a woman, and rarely do they actually focus on other organs, the heart being the most important one, of course. You’re talking with a cardiologist right now. But again, our question is, how do we really move beyond the bikini and protect a woman’s heart? Heart disease remains the number one killer of women. In fact, breast cancer is only the fourth leading cause of death of a woman. And it actually is 10 times more likely to die from heart disease than you are from breast cancer. And so we need to really critically look at what do we know about women and why do women not do as well after they actually have heart disease? Now, part of that is because we haven’t really included women in a lot of trials. And like I said, we’re only putting playing catch up in the last two decades. And so we still we’re getting more data and it is an exciting time to be in this field, but we still have a lot more data we need. And I love this cartoon because, you know, they say we have studies of fruit flies, mice, hamsters, frogs, monkey and men with this condition. But medical research using women as subjects just never really occurred to anyone. And that was really the case. When we talk about heart disease. So we look at this actually, we we periodically look at our data to see how many women have been enrolled in studies in this particular study. Corrected for the prevalence of the disease. And they showed up for atrial fibrillation, for hypertension, for pulmonary hypertension. We’ve actually done a good job of getting women enrolled in those studies based on the prevalence of the diseases, but common things being common: coronary artery disease, acute coronary syndrome, heart failure, the commonest heart issues that exist in our society. And we still have not enrolled enough women. And a recent study was just done and released a couple of weeks ago and they showed the same thing, the same trend. So this was from 2018, but I can tell you the 2020 data showed very similar findings that we that the commonest cardiovascular disease still don’t have enough women in the trials. Now because we’re talking about sex differences. I just wanted to take a second to point out the difference between sex and gender. And I will admit that our society in general tends to use these interchangeably, but they’re not really the same. Gender is a socially construed concept. It means when society looks at a woman, they see a woman and they might treat a woman differently than they treat a man. But sex is biologic. If you are x x, you are a woman. If you are x y, you are a man. And both are important to how we treat women because there’s things about gender that influence care. But biologically, how our body responds, how our body responds to stresses, how our body responds to insults, things like hypertension, or whether we respond differently to smoking effects and hormonal differences. That’s all biological, right? So we just need to make sure when we’re talking about sex, you understand we’re talking about the biological differences. Even though gender always comes into play. Now, why this is important, Why is sex important? Well, even, you know, we we’ve been saying for a number of years that it’s important that we enroll women in trials. And that was in the in the, uh, I guess in the late 90s that it was mandatory for to get NIH funding, you had to include women in your studies to get the NIH funding. Interestingly enough, though, we didn’t make it mandatory for cell studies or animal studies, and that was only realized in 2014 that most of the studies we have are male animal studies or in cell lines. They were often using male cell lines. And so in 2014, the NIH, which included Janine Clayton and Francis Collins from the NIH, they said, you know, we really need to have policies about the animal in cell studies. And they did actually make this mandatory as of 2016. So now studies we are seeing of animal and cell lines where they do have to report sex and they have to include both sexes. And this will make a difference for us because really the way that we do research, right, we do cell studies in animal studies and then human studies, and we already know that there’s difference is based on cells or based on animal studies, it might help us know what will actually happen to our our women, our population. And the great thing about animal studies is, you know, animals, mice, for example, get pregnant. And that has always been a reason to exclude women in trials or hormonal issues. But we need that data to be able to take better care of women. So like I said, I told you that women, after they have heart disease, after they have a heart attack, they do less well than men. And I want to take you through some of the things that I think may impact why women do less well. So the one question I would pose is whether we even follow the guidelines equally in women compared to men. And we have data from our Get With The Guidelines or the MTVR data where volunteer hospitals give their data to us to say, you know how well they’re performing. And this was a specific study looking after all types of heart attacks. And they found that they’re looking at the odds of a woman getting a treatment. So in this middle column here, the adjusted odds ratio that you can see if it’s greater than 1, it means a woman got it more likely. If it’s less than 1, it means a man was more likely to get it. And if it was equal to 1 it means that men and women were equally likely to get it. Well, you don’t see a lot of 1s because women were less likely to get aspirin or beta blocker within 24 hours. They are less likely to undergo any type of invasive procedure. They were less likely to meet our standards of door to balloon time or door to needle time or undergo any type of acute reperfusion therapy. The only thing women were more likely to do is die, and specifically the ST elevation myocardial infarction group were the ones that were statistically more significant in terms of likelihood to die. We’ve looked at this repeatedly in stratifying by younger women, younger women, so under the age of 45. So see if there was a difference on how they got treated. And really it was just being a woman. Actually, the age didn’t matter. So much, at least with the Get With The Guideline data. We looked at race as well as sex. And after this particular publication and we again, it was worse to be a woman, but it was worse to be a black woman. So there is discrepancies in how we care for women and that we aren’t color blind as well. And these things need to be addressed and discussed in hospitals so that we can overcome our biases and are aggressiveness in treating men and women equally. Why does it matter? Well, we we do know that women are more likely to be rehospitalized after a heart attack, and specifically younger women. So if you look at these curves, you can see women are showing gray, men are shown in black, and the younger men and women are shown in the solid lines and the older men and women are shown in the dashed lines. And you can see after having a heart attack, women are more likely to be rehospitalized, particularly the younger women. And this happens starts right after within the first month. You can see there there’s a difference. But when we follow them out for a year, these curves get wider and wider. It is true that older women get more, are more likely to be rehospitalized than their same age men. But if you’re under the age of 55, it’s even more likely. Some of the things that I had proposed for us to get away from, you know, to get away from the bikini is that when people do have a heart attack, specifically the ST elevation myocardial infarction group, of course, we need women to be more aware. And that’s certainly something we all need to address. We need to do public health education so that they get timely care and they get to the hospital quickly and know to call 911. But we also need health care providers to be aware of these discrepancies in care. And we also, if we used standardized protocols and I couldn’t get into all of that today, but there is evidence that when when you use a standardized protocol where an emergency room or, you know, knows that this has a checklist and make sure everything gets done, we know that improves outcomes and it narrows the gap between men and women. Now, there is some role of artificial intelligence that might also improve our care. And so I’ll discuss a little bit about that later. And then, of course, we need more research on women and that will also help. These are things in ways that we can actually improve outcomes after ST elevation myocardial infarction. The other question, though, that I would like to pose is whether women experience a heart attack like men. What is the sex differences in diagnosis? Now, some of you might be familiar with this term called Yentl syndrome, and Yentl was a story. It was a story of a woman who wanted to study the Talmud, the Jewish rabbinical studies. And in order to be taken seriously, she had to disguise herself as a man. And if you didn’t read the book, there’s a movie, too, starring Barbra Streisand. And so she disguised herself as a man to be taken seriously. And Dr. Bernadine Healy, who was the first female director of the National Institute of Health, said, you know, is this what we have to do if we only present like men? Is that the only way we will be taken seriously? And she is the one who made a push to include women in trials and actually was the reason that the Women’s Health Initiative ever got initiated. But her point was that the assumption was that if women and diseases present, if women only present like men, that’s the only way they’ll be taken seriously. We need to know if women differ. Now, in terms of the sex differences in presentation, you know, the typical description of angina was a definition based on men. And in the past we thought women might present more atypically. And that term atypical has been used quite frequently. The additional thing was that women often didn’t have obstructive disease, and in the past we used to call that and that that was like somehow a false positive. We know that’s not the case anymore. So, you know, we’ll get into that in a little bit. But the question I want to at least pose right now is whether women truly have atypical symptoms because unfortunately, we’ve convinced women that they don’t present in the same way as men. And there’s many female patients that will go come to us and say, well, I was having chest pain or chest pressure, but I understood that women present atypically so this could not be a heart attack. We do not want that as the public health message. We also have data that actually symptoms are there. There’s differences between men and women, but some of the more typical symptoms are actually quite often seen in women. So for younger women, we have this study called the Virgo Study. It only looked at people who had an ST elevation myocardial infarction, who were under the age of 55. Men and women. And what they found is that 90% of young women and men presented with chest pain, chest pressure, chest tightness or discomfort, the difference between men and women was that women often had 3 or more additional non chest pain symptoms compared to men. So meaning women were more descriptive. And I don’t know, we didn’t always think we heard the words chest pain because we got lost in the other symptoms. But certainly when you record it, they do report the more classical symptoms. Now, when women did present, it was more likely that women would be told their symptoms were not heart related. Um, and I’ll show you that data. Oh, actually, I won’t show you that. Yeah, but that was the more frequently seen that women would be more dismissive. And these are people, again, in that prior study in Virgo, they all went on to have an ST elevation myocardial infarction, but women compared to men, if they saw a doctor preceding it, preceding their heart attack, they were more likely to be told it wasn’t related to their heart compared with men. Now there was a great study shown at EFC in 2019 in Paris, and this study was called the HERMES Study. We still haven’t had the publication come out yet. I understand it’s under review, but this study was looking at all women and men who presented with different symptoms and what they used artificial intelligence to listen in to the conversation. That artificial intelligence used cardio linguistic technology that picked up what is the patient in the room saying. And what they found is that 90%, again, of women reported chest pain. And again, women were more likely to report other symptoms along with this. So the atypical symptoms were certainly more likely seen in younger in women. But their prevalence overall was quite low in women and they were also reported by men. So we just need I think I what I’m trying to make a case for is we need to move away from this label of atypical. And part of the reason is, is because atypical means a different presentation from normal. Unfortunately, the way it’s got translated in our medical community is that when someone says this person has atypical symptoms, what they usually mean is that it isn’t heart disease. At least that’s the way it’s used commonly when we’re on the floors and when our fellows or residents come up to us and tell us about a patient, when they use those words, they usually mean, I don’t think that this is the heart. We had another study EFC that was presented also that calls that I didn’t show here, that also was simultaneously published and it showed the same same thing that women were 90% of them presented with the typical symptoms. Now, when we use our high sensitivity troponin, which a lot of our labs have changed to high sensitivity troponins across the United States, and if they haven’t moved, they’re in the process of moving. But we do know that prior measurements of troponin, we didn’t have sex specific thresholds. So with the high stakes group from the from the UK, they actually showed that when you use the 99 percentile cutoff for women compared to a 99 percentile for men, we actually improved the sensitivity of the test in women, but not in men. Well, makes sense, right? Because the heart is smaller in women and it would make sense that they would actually leak out less enzymes than men. But we were never using sex specific cutoffs with the prior troponin values. Now, with a high sensitivity troponin is not only are they highly sensitive, but a lot of labs have moved to sex specific cutoffs based on this data and data that is being replicated in the United States as well, although we’re at the earliest stages, whereas in Europe they had already switched to this and they showed that we improved the sensitivity of myocardial infarction, detection in women from 13% to 23%. And in fact there was really no change in in men. So the sensitivity actually increased to 95% in women. The other differences about sex that exist is like even just when women have cardiac arrests, when they have a cardiac arrest out in the public, it may surprise you to know that A by somebody that’s standing by and witnesses, a cardiac arrest is likely less likely to initiate CPR on a woman compared to a man. And we know if you don’t initiate CPR quickly, we’re less likely to save lives. So that’s why it’s such an important issue. It’s less likely that a woman, compared to a man, will get attempts at defibrillation as well. And therefore, it’s less likely that women would recover compared to men. Although we all know when somebody has a cardiac arrest, essentially they’ve died. And if we can save any of them, it’s a victory. But certainly it’s more likely that that would happen in men compared to women. Now, there’s many reasons for why people won’t initiate CPR on a woman. Biggest reason is they’re scared of hurting women and they’re scared of being sued or touching a woman’s breast or exposing a woman. The fact is, if they’re scared of hurting a woman, we we do need to educate them so that they know that, you know, if you don’t break a few ribs, you won’t save lives. In fact, we know that that’s how we know good CPR has been applied. Also, the Good Samaritan law exists and exposing a woman’s breast to do CPR it’s certainly something I think any woman would argue, I’d rather you do that to save my life. Now, the other thing is, though, when we all learn how to do CPR, usually we’re trained on the Annie doll. She does have a woman’s name, but she doesn’t look anything like any woman I’ve met. And unfortunately, not being anatomically correct has been a barrier to helping the public understand how to do CPR on a woman. So I always say, you know, we have enough mannequins. We now need the womaquins, because that’s going to help us take better care and teach appropriately how to do CPR on women. Well, so the other question I would pose to you is whether our guidelines even apply to women. Is that part of the reason that women don’t do so well? Well, we have guidelines called the stable ischemic heart Disease guidelines from the American College of Cardiology, the American Heart Association. And these were released in 2012, and they were last slightly updated in 2014. But the whole point of that, that flow diagram, you don’t need to read all the details in it. But what I wanted to point out is basically they’re all leading up to who should we do angiography on, who should we send to the cath lab with the overt focus on obstructive coronary artery disease. But the fact is, as we know for women, you can go on, you can have stable ischemic heart disease and not have an obstructive lesion, unlike that diagram to the right. That diagram on the right is the one that I learned from when I was a medical student, as though you could only have an abnormal stress test when you have an obstructive lesion that you could see in a large coronary artery as though you would only have symptoms at that stage. And we now know that is not true. So we need to change how we educate people and we need to change these notions and we probably need updated guidelines. So the we need to we need to actually, you know, talk about that from a cardiovascular standpoint in terms of obstructive coronary disease. We know how to treat that. And we tend to call that male pattern, whereas the female pattern of cardiovascular disease or can be in the micro vasculature. And we now have new terms for this called INOCA or MINOCA. INOCA stands for ischemic with no obstructive coronary artery disease in MINOCA is myocardial infarction with no obstructive coronary artery disease. The fact is. I’m sorry. The fact is, is that when we are as we talked about at the beginning, sex matters, biology matters, x, x versus x, y. Um, but that matters that every organ I’m only talking about the heart mostly here, but kidneys, the brain, all of this can be affected based on sex. Every risk factor has a different effect based on sex. Even our hormones that run around in both bodies in different amounts, again, affect organs in different ways and can affect the entire response system differently. But I just want to remind everyone that every cell has a sex. So that means we differ across all organs from our brains to our hearts, to our lungs, to our joints. It doesn’t matter. Every cell really has a sex. And that’s why it’s important that we even study women, because we do need to know this information. But I am a preventive cardiologist, so I’m going to now spend a little time talking about how we can prevent heart disease, because 80% of heart disease is preventable. And we know that risk factors can affect women differently than they do, man. And so important to be aware of these differences and know what risk factors actually even matter to women. So we have the risk calculator that many of us use, the ASCVD risk calculator. And you know, the only real difference in there for women and men is the the first tab, you choose the gender, male or female, and then you can estimate their 10 year risk, which is the short term risk, and then you can estimate their lifetime risk. And it’s been well validated both internally and externally validated. But as of 2018, they updated this further, not so much the calculator because the calculator stayed the same. But the recommendations in the 2018 cholesterol guidelines actually labeled risk enhancers, meaning things that you should also take into consideration that aren’t part of this calculator that may move a patient to a higher risk category. And I’m going to talk about them in a bit, but let’s just talk about the traditional risk factors, because even they have sex differences and I don’t think those are always appreciated. So although it’s less likely for women to smoke in our U.S. population, the problem, the relative risk of smoking actually is greater in women. So women or women who smoke the same number of cigarets as a man will have actually more vascular effects. Another disease, diabetes is much more common in women. And a diabetic woman compared to a diabetic man is much more likely to develop cardiovascular disease. Also, there is sex specific stuff like gestational diabetes and polycystic ovarian syndrome that I’ll talk about a little bit later. But those are things that obviously only happen in women. Hypertension, again, is actually as women age, it’s more prevalent in women than in men. And they may actually have more vascular effects as well. If you’re a hypertensive woman, that seems to be a little difference related to cholesterol. We have some data supporting that. Poor physical fitness may have actually more cardiovascular consequences to women than men. You know, things like depression actually have a greater effect on women and also have greater effect on specifically related to secondary prevention, lupus and rheumatoid arthritis, autoimmune diseases, are actually much more prevalent in women than in men, and they are known to have severe cardiovascular disease as a result of those inflammatory states. Let’s just talk about blood pressure. Just I want to point out a really interesting study that was just released a few weeks ago, because we commonly used to tell people that when blood pressure rose, it was at the time of hypertension, most sorry, blood pressure rose it was at the time of menopause for women. But this interesting study actually showed the trajectory of blood pressure changes for women compared to men. Women are shown in most sort of orange red line and men shown in blue. And you can see that especially for systolic blood pressure, the trajectory of blood pressure, even though a woman starts off with a lower blood pressure, systolic blood pressure, her trajectory is actually much more rapid than a man’s. And that may have some consequences and it may even imply that we don’t even know the right threshold or cut off of blood pressure in women. They’re used for cohorts, population cohorts from the United States, and they mapped out their height, their blood pressure over time and saw these trajectories, which really is interesting. So our assumption that something got turned on at menopause may not actually be correct, particularly based on these population studies. So we need to keep, again, more more evidence that we need to keep studying women. And there may be this this difference based on sex simply for blood pressure. Now, I talked just briefly about the risk enhancers, and they’re shown here on the guidelines that that were released in 2018. And some of the risk enhancers, of course, that are common are things like family history and persistent elevation in LDL, chronic kidney disease and metabolic syndrome. But specific to women are some things that occur in only in women, things like pre-eclampsia or any type of gestational hypertension, mention premature menopause. Then there’s things like inflammatory diseases. Like I talked about lupus, rheumatoid arthritis, which again are conditions that are more common in women. Certainly ethnicity like South Asian ancestry does matter. And so it’s important that we ask about those things. And then there’s other selected studies that they might already have or they might get done and we’ll talk touch on them briefly, like high sensitivity, C-reactive protein, LP(a) elevations, ApoB elevations, all of that. And they may come with that, so that may be considered a risk enhancer. And I just want to discuss a little bit about those and the sex differences where they exist. Here are the risk enhancers again listed just so that you could see I wanted to just blow it up so that you could see it in basically that’s what we’ve been the entire chart over to the side on the left, just in case it was hard for some of you to read depending on how you’re watching this. So so C-reactive protein we have known for since we were studying this biomarker that women had higher levels compared to men in general. And you can see that shown here. This here it’s stratified based on race because there is racial differences as well as you can see. African-American men have higher levels compared to white men, and that African-American women specifically have the highest levels. But women in general have higher levels. And again, this is just stratified by body mass index and by race and by sex. So you can see that there’s a sex difference, a race difference, and of course, by body mass index, there’s more marked inflammation. This is a marker of inflammation. And it’s important to know that there is actually different levels for men and women. Now. LP(a) is something that we’re doing more testing on, particularly in certain populations. There are actually there isn’t much difference in terms of LPA, LP(a) levels in women compared to men. They sort of run the same and that’s important for us to know. But again, the reason that we can we’re concerned about LP(a) is that there’s a higher risk of nonfatal myocardial infarction and coronary artery deaths in those with higher levels of LP(a), and the same is seen in stroke. And so that’s often why physicians might check LP(a) or order LP(a). The only thing about LP(a) is that we don’t necessarily have a treatment. There’s some suggestion that PTSK9 inhibitors may reduce LP(a), but it isn’t consistent and we still need a lot of more a lot more data on that. But it certainly is a marker that I see more and more patients will either come with it, it’ll be ordered by their physician or you know that somebody has done it for some reason. So we at least will address it. And sometimes we feel like in certain ethnic groups it may be useful to check some of these inflammatory markers just to risk stratify better. ApoB vs another one you can check an ApoB, you can also just calculate the non HDL. There’s a lot of data supporting that non HDL, which is just your total cholesterol minus your HDL. That would be enough to actually mimic what we find on ApoB, ut some people like to see the ApoB, so they might order an ApoB. You use it in the same way. Other things that we need to take into account, though, for women specifically are things related to their pregnancy. I always say that pregnancy is like nature’s free stress test, so asking about their pregnancy and complications that occurred will help us. It helps identify women who may be primary prevention efforts might improve overall ASCVD risk. What are those adverse pregnancy outcomes? Things like preterm delivery, gestational diabetes, any type of hypertension during pregnancy, not just limited to pre-eclampsia and eclampsia, but any type of gestational hypertension? And then also there’s some data supporting small for gestational age or fetal growth restrictions. Are those first for the ones that we probably have the strongest data, because macrosomia or a large fetus, a large baby or multiparity, those are influenced by a lot of other different things that ultimately can affect cardiovascular disease. We don’t know if it’s those other things or if it’s somehow pronounced by these issues,. But nonetheless, 80% of women in the United States bear at least one child, and about a third of them will have one of these adverse pregnancy outcomes. So again, important to be asking about that when we take a history. We don’t exactly know what is occurring. Is it because they have risk factors present prior to pregnancy that something gets activated in the placenta and causes the issues that we see or if it’s something that’s turned on by the pregnancy and makes them puts them at risk? And there’s a lot of research going on in that area right now. But that, I think, is an important emerging area that we are identifying women at this time, especially when they’re under the care, health care at that time, at least at delivery, if not pre-delivery, we are taking care of these women and identifying them at a stage that we can make a difference, hopefully. The other thing is to recognize that breast cancer, we’ve done a great job at treating breast cancer. Women do quite well now with it when they’re diagnosed with breast cancer. But a lot of times what they’re more likely to die from is actually heart disease. Part of that is because there’s some shared risk factors for heart disease and breast cancer. Additionally, some of the therapy we give, chemotherapy and radiation therapy increase the risk for heart disease. So we need to be actually educating women not just about after they get their therapy for breast cancer to understand, you know, what surveillance is needed for breast cancer, but also what surveillance is needed for the heart and a great opportunity to intervene then and at least measure their cardiovascular risk and communicate that risk to patients. So my approach for women is this. I assess their atherosclerotic cardiovascular disease risk using that risk calculator. I assess risk enhancers. I include family history and race and ethnicity at that point. Another high risk group that I didn’t talk much about here or any at all here was veteran women, but they are actually considered a high risk group because they tend to have more cardiovascular risk factors. So taking that into account, then I address the sex specific risk factors that we talked about. Things like adverse pregnancy outcomes, about premature menopause, about hormone replacement therapy, or if they’re on the birth control pill, particularly those who are on the birth control pill and smoke are at much greater risk. I talk about whether they have breast cancer, chest radiation in general. Then I talk about female predominant conditions like lupus and rheumatoid arthritis. They think that’s how we personalize it for the patient and we’re not going to do fancy genetic testing overall. There’s not like just one genetic test anyway that can tell us if you’re at risk for heart disease or not, at this time. And it’s also right now, not at the point that we know the right genetic test to do for people. The way we start the genetics starts with are you male or are you female right now? And if we started with that, we would do better. We would take better care of women because we would recognize the sex differences in cardiovascular disease. So in summary, I hope that I have convinced you that there are sex differences that women and specifically women we know do worse after having a heart attack. And, you know, if we just adhere to guideline directed therapies, we would do better with women. Younger women are at the greatest risk right now after having a heart attack. They have the greatest likelihood to die. And we need to know what that why that is occurring. And so we need a lot more work in that area. Certainly symptoms, I hope I’ve convinced you that symptoms are often typical in women and we really need to move away from calling them atypical because somehow that connotation has a different meaning that wasn’t intended. And also the data is supporting that women are more likely to have those typical symptoms anyway. We should work on prevention. We are in health care, and health care doesn’t mean sick care. So the better we can preserve cardiovascular health, the better. And if we take into account the sex specific atherosclerotic cardiovascular disease risk factors, it will help us take better care of women and identify the women that are at a higher risk. And of course, we must demand more research on women’s hearts so that we can really understand a women, a woman’s heart better. So I’ll leave you with this, that women, there’s just a lot more to understanding women. This was outside of my house on Halloween. My husband thought he was quite funny to say that was supposed to be him as the skeleton that he was still waiting for me to be ready. So I will end there and I guess we will take questions. I think. I don’t know where the slide is, so I’m going to release the controls to other people. But there there was supposed to be a slide about if you’re interested in being involved in research that the American Heart Association actually has an initiative on research. So we’re trying to enroll women and get them into different trials. So there’s a I don’t know if somebody can put up that slide of how they people could enroll if they were interested. But if you do have questions, certainly there’s a way to chat. So I’m going to wrap it up here. I see one question that somebody is asking, which is a great question, and the only question I can see right now is where do transgender people fit into this picture of cardiovascular risk? And I and have studies been done to include them? We have a little bit of data about transgender people. And this is a great question because this is going to be if we don’t study them, we’re going to have a new area that we’ve been understudied and won’t know what to do with them. But there is a small body of literature, most of it coming out of L.A. from Cedars-Sinai, and that really is limited data. What we know is that transgender women so meaning a man who has changed to a woman, is the highest risk group. The reason that the data is in which we still don’t have answers on what we should do or any of that, and it’s going to be a really hard area to really understand because understanding the transgender population and after I sat through a talk about this, I learned so much about it after understanding that there’s a couple of things that go on when people undergo transgender treatment. First of all, everyone’s treatment isn’t entirely the same. Their choices about surgery is not the same. What they get removed what they, you know, even from sex organs to things that you can see that you can’t see inside, you know, whether they remove testes or not. That’s all a decision that an individual takes makes. Additionally, even their hormone regime isn’t necessarily even what the doctor prescribes. There’s an incredible black market if you will, about hormones that they will take and they will take things off the street. Sometimes they can’t afford the medications that are being prescribed for them. Sometimes they feel like they aren’t getting the right amount of estrogen, that they want to feel like a woman. So they will take things. And that’s really making it a little bit complicated. But certainly one of the most important questions I have. So I appreciate whoever asked that question. Thank you. I think we need to collect data on that population. Thank you so much, Dr. Coletti, that the message, the questions are coming in fast and furious now on the chat. So we will we will get to those immediately. But before we do, Operator, if you were there, if you could just read the instructions for live questions? Certainly we will now begin the question and answer session. For participants, if you would like to ask a question, press star then the number 1. Please unmute your phone and record your name slowly and clearly. Your name is required to introduce your question. To cancel the request to me press star and the number 2. Once again star 1to ask your question and star 2 to cancel the request. One moment please, for any questions. Thank you very much. We have several questions coming in. Dr. Coletti. I’m not sure if you can see them, so I will I will triage those for you. How do how do you further assess inflammatory markers for women, especially in autoimmune diseases? And do you use any cardio genetic testing? Oh, so, um, in autoimmune diseases, you know, that is inflammatory disease. I’m not going to ever be the expert on what markers of inflammation the rheumatologist is checking on them. And it is, but if you’re asking specifically, of course, their C-reactive protein is going to be elevated as is their high sensitivity C-reactive protein. Remember, it’s just a marker of inflammation. So when they have an active disease state, you’re going to see all the markers of inflammation like C-reactive protein to be elevated. It really for that population from a cardiovascular standpoint, doesn’t matter what their markers of inflammation are, meaning certainly if the disease is active, it matters to the patient and obviously to the rheumatologist. From us, what I need to know is that they have lupus or they have rheumatoid arthritis because that that’s all I really need to know. That that tells me they have systemic inflammation and that they’re at a greater risk of cardiovascular disease and that this is a group that you need to identify and assess and measure all their cardio vascular risk factors. So know what their cholesterol is, know what their blood pressure is, talk about their weight. You know, talk about all the risk if they’re diabetic or not, you know, and make sure they know they’re at a greater risk and then try to identify if you can see this disease early, that might be somebody that you would consider for testing like coronary artery calcium testing, because they have an accelerated risk for cardiovascular disease and then do everything you can do to reduce any risk factors that are present. Thank you very much. Do you, in your experience, does anemia have an effect on heart health for women? Complicated. Usually anemia, sometimes you can be anemic because you have some underlying condition. A great example of that is somebody with chronic kidney disease or end stage renal disease, as many of you probably know that a lot of them have anemia due to certain conditions. So they might yes, they’re anemic, but they have chronic kidney disease, which already puts them at a higher risk for cardiovascular disease. So in and of itself isn’t as meaningful because hopefully you’ve done a good history and you know these other things about them. Now where anemia may have direct effects on the heart, it’s a little bit during pregnancy in the sense that, well, when you’re pregnant, you run anemic anyway. Just because you’re you’re you have extra plasma volume, you try to make extra red blood cells. But women who are pregnant tend to run a little bit anemic anyway. But if you’re profoundly anemic, there may be some contribution to things like heart failure at pregnancy that there’s some association with that. But in general, anemia in and of itself, we always ask why. It certainly can aggravate things in somebody who already has cardiovascular disease, for example. It it may like, so if you have anemia and you have some coronary artery disease, you may be more symptomatic when you’re anemic, say if you have an acute blood loss or something like that, or even if you have chronic anemia, but you’re in your anemia is getting worse. It so, you know, ultimately blood carries the oxygen. So you certainly need a certain amount of blood in the body so that you get the oxygen everywhere. And it may be a little bit more limiting when you have atherosclerosis already present. Thank you. Is is family history incredibly difficult to overcome or can a woman offset the genetics with diet and exercise? And then of course, a lot of questions about diet. Okay. Yeah, that’s a great question about genetics. And I think the reassuring data was a study a couple of years ago in the New England Journal of Medicine where they actually did take a high risk population and did genetics on all of them. And what they found in that study they just they also then asked that population of high risk folks whether they did any of their healthy behaviors. And they were quite liberal with the term healthy behaviors because their definition wasn’t very strict. It was like, yes, did you actually. But it wasn’t that if you exercise to our current guidelines, it’s just exercising a short amount per week. And if you ate relatively healthy and, you know, other healthy behaviors. What they found in that study was even if genetics pointed to you to be very high risk, the people who did just some of the healthy behaviors were more or were less likely to develop heart disease in the future. And those people who did all the healthy behaviors were, again, even the least likely to develop heart disease in the future. So you shouldn’t be resigned just by okay, I have a bad family history. I’m you know, I’m going to die from heart disease. No, no, no. In fact, the opposite. It is even more important because even a little bit goes a long way. So when we’re counseling patients with strong family histories, it’s not all doom and gloom. And there is things that people can do to empower themselves and to feel like they’re in control. So by controlling risk factors, by controlling diet, by doing exercise, that will actually be the difference. So genetics is only one part of any disease, just the gene itself doesn’t mean it will announce itself or pronounce itself. And you said those questions about diet. Was there a specific question or somebody’s going to ask me the crazy question of which diet is best. Nobody asked that directly. But what several people have asked is there what type of diet do you recommend? Okay, Well, then they’re asking what type of diet? Yeah. And I know we all get asked this question on a daily basis about what is the diet? What is the diet every day? You know, today I woke up this morning reading a study that breakfast isn’t good for you. And then the day before I read a study, that breakfast was great for you. And so, anyway, you got to it’s hard. Dietary studies are very, very hard. I think the my recommendation about diet is to follow basically, the Mediterranean diet, which is heavy in fruits and vegetables, using olive oils and omega threes and limiting the saturated fats. You know, low fat dairy is okay. Red meats quite limited. You know, I think the Mediterranean diet probably has the strongest evidence. So that’s what I recommend. Certainly I, when I tell people to be more plant based. And I’m not just saying that you you know, I’m not trying to push my values on anyone. I am vegetarian, but I do think that you should be more plant based. But I don’t want to say more plant based. I’m still allowing people to have meat in their diet. I just think you should introduce more plants. So what I tell patients is we talk about how many plants do they eat every day? Do they? Because again, if if half your plate should be some, you know, some form of vegetables, most of my patients anyway, I’ll just you do not actually report that. So there’s always room to add more plants and plants as well as a source of protein is it’s certainly a good idea, but it’s not the only thing. And I don’t you know, I think fish has many beneficial properties, so if people want to eat that, that’s great. If they need to eat meat, that’s fine. But just to introduce more plants and follow more of the Mediterranean diet in their life in general, it doesn’t mean you can’t have an occasional indiscretion, but it just means that we should mostly follow it. I do think there’s more and more evidence that sugar is not our friend and we do as a society, we’ve just started consuming more sugar. If you look over time, it’s no longer the luxury it was back in the turn of the 1900s. And so now we consume lots of sugar in lots of different things. Sometimes you don’t even know you’re consuming it. So with that that is certainly part of a problem for us related specifically to diabetes, but can also translate to worsening your cholesterol. So the more we can limit those kind of substances or foods in our diet, the better. And I with every patient I again, I try to empower them to make one change at every visit so that, you know, we can gradually make the changes if you just tell them to change everything, that usually won’t stick. So I actually asked them, what’s the one thing that you think you can change after today? If we’re talking about diet or exercise, what is the one thing you can introduce and make those wins? If they can stick with that for a while, then the next visit introduced something else.