Sammi: Good evening everybody and welcome to this evening’s Women and Heart Disease webinar. My name is Samantha and I am your host for this evening. Before we get started, I would just like to make a quick Acknowledgement of Country. We recognise the traditional custodians of the land and sea on which we live and work and we pay our respects to Elders past and present.
I would like to introduce our presenters for this evening. So we are joined by Professor Jon Hyett this evening, and Jon is the head of High Risk Obstetrics at Royal Prince Alfred Hospital and Clinical Professor in the discipline of Obstetrics, Gynaecology and Neonatology at the University of Sydney. He has an interest in screening and preventing preeclampsia and ensuring women affected by this disease have appropriate post-partum follow up. We are also joined by Dr Clare Arnott. Clare is a cardiologist at Royal Prince Alfred Hospital and a Senior Clinical Lecturer at the University of Sydney. She has a special interest in women’s cardiovascular disease and the long term risks associated with hypertensive disorders of pregnancy and runs the Women’s Heart Clinic at the Charles Perkins Centre. And we are also joined by Dr Linda Mann this evening. Linda will be our facilitator. Linda is a Fellow and a member of the RACGP and a member of the RACGP Antenatal and Postnatal Care Network. Linda has both local and international medical experience, especially in genetics and women’s health. She is a GP representative on various national and local government committees and is an experienced medical educator. So, welcome to our presenters this evening and I will hand over to Linda now to take us through our learning outcomes for tonight.
Linda: By the end of this webinar, we hope that you will be able to summarise the current evidence base of the relationship between hypertensive and metabolic complications in pregnancy and cardiovascular risk. That you will be able to use existing evidence and tools to appropriately advise and manage female patients in relation to cardiovascular risk, and that you will be able to deliver clinical care that reflects current sex-specific differences in the pathogenesis, presentation, management and outcomes of cardiovascular disease.
Clare: So, thanks for joining us tonight. I am Clare Arnott and I am a cardiologist. Obviously, women’s cardiovascular disease I believe is extremely important, or a gender-specific approach to cardiovascular disease, and it is gaining a lot of traction nationally and internationally, and I hope that I can convince you of that tonight with Jon. And that is really because women truly do behave differently to men in terms of their presentation, in terms of the pathophysiology and in terms of responses to treatment and outcomes. So, hopefully we can convince you of that.
To start with, I just wanted to talk a little bit about the burden of disease. So cardiovascular disease in Australia, and indeed worldwide. So, CVD is a leading cause of death in Australian women. I say a leading cause, some statistics would say the leading cause. And that is not just in elderly women, that is in all age groups in adulthood. And just to give you a rough figure, if you look at 2016, CVD accounted for 28,000 female deaths and that was 34% of all female deaths. So we are not talking about a small proportion of the kind of morbidity and mortality that we see in Australia. And beyond deaths, if you actually look at disability adjusted life years, it is also a very, very important disease. So globally in 2016, CVD went first in terms of DALYs, and in Australia, fourth. If you kind of hone a little bit more down into the details of the differences between sexes, what we see is that annual death rates between males and females are similar. However, if you look at in-hospital deaths, they are actually higher for women than they are for men.
There is also a few other differences. So women tend to have high rates of heart failure and higher rates of stroke than men. But interestingly, or importantly, they typically present about a decade later than men. So, to give you an example, a woman of 50 will have a similar absolute risk of death from cardiovascular disease or presentation with cardiovascular disease than a man at 40. So, if you look into the condition in women in a greater depth, there is a lot of disparity. So, as cardiologists one of the benchmarks that we look at is what we call pain to door time and what we call door to balloon time. So pain to door time is, from the moment that you get that crushing central chest pain or whatever it is that is your symptom, the time that it takes you to get to the door of the hospital, and then door to balloon time is the time from arriving there that you get to the cath lab and you get your artery opened if you are presenting with an acute coronary syndrome. And whichever parameter you look at, women do worse. So, women present later than men with acute coronary syndromes and I am showing you some statistics from quite a beautiful study that was done in Melbourne that showed that women presented, from the time they got pain to the time they got to the hospital door about an hour later than men. And that is an interesting discussion point in terms of why, and I do not have the answer for you. Some people think that it is because women have more atypical presentations. Others think that it is because women are less likely to prioritise their cardiovascular health or understand that it is relevant to them. Once women have presented, they are actually far more likely to experience complications of an acute coronary syndrome than men are. They are less likely to have an intervention. So women are less likely to actually get to the cath lab than a man is. And overall, they actually have a worse prognosis.
Now that is all women. If you then start to look at some of our more disadvantaged populations, so women in rural populations and those in lower socioeconomic parts of our society or Aboriginal and Torres Strait Islander women, they have a far higher mortality. So really, if we are going to get serious about dealing with this disparity we need to look at what makes women different and what makes women special. And just to sum that up, I have put out some startling statistics in terms of health expenditure, and that is from 2012 to 2013. So, if you look at the 1.3 billion that is health expenditure on men for CVD as distinct from 636 million for women.
So, Linda and I discussed this slide and this may sound completely old to you or it might be completely new to a lot of people, and that is the fact that not all coronary disease, or not all cardiovascular disease is obstructive coronary disease. So, you know, the previous thinking was that when someone presented with angina, they had blocked coronary arteries or they did not have angina. And we now know that that is not the case. Particularly in women, there is beautiful data that has come out from many studies, including the WISE study, and I do recommend that people have a look at the WISE study. It is old, but it is beautiful data, and it shows that women are less likely to have angiographically obstructive disease than men, but that does not mean they are less likely to have angina or indeed heart disease.
So there are a lot of conditions that we need to think about as cardiologists and as general practitioners in addition to obstructive coronary disease. And these are things like spontaneous coronary artery dissection, which are very relevant particularly to our young women and I recently saw some data that in the less than 40 year olds, SCAD probably is responsible for about 40% of acute myocardial infarctions in women. Coronary vasospasm, microvascular disease and endothelial dysfunction are all conditions that we know are more relevant to women. They are harder to diagnose. They often present more atypically, but certainly they are very real and we need to be more cognisant of the fact that our women may be suffering from those conditions. And the other one that I have popped there which is relevant to men and women, is myocardial bridging. Now, I am not sure if we are going to get a lot of questions on this slide, but I suppose the important thing to say is not that I think that everyone needs to know how to diagnose these conditions, they are very difficult and it is quite a pathway to diagnosis in many of them, but just to keep thinking broadly. Do not think because your patient has had a negative stress test or a normal CT that they cannot be suffering from angina. And be an advocate for your patients. So if something does not seem right, refer them back to the cardiologist or get a second opinion. I think one of the things that we all struggle with is this idea of kind of Bayes theorem that it is the pre-test probability that is so important when you are looking at whether someone may have a condition, and we are kind of all conditioned to think that the pre-test probability of a woman having heart disease is low and so I hope I can change that for you tonight, because it needs to be in the forefront of what you are thinking when you assess a woman who has chest pain or who has dyspnoea or who has a reduction in their exercise tolerance.
Another issue that I think is very important in female populations is awareness. So, some statistics that were done in Australia in kind of 2014, was that only 24% of kind of young to middle aged women, were aware that cardiovascular disease was a leading cause of death. So in that context it is hardly surprising that women are less likely to present with acute coronary syndromes or that there is a delay to presentation. Because if it is not on your radar, you are far more likely to think that you are suffering from reflux or musculoskeletal pain. Linda?
Linda: Can I just interrupt you a second. In relation to the previous slide, could you explain to us what myocardial bridging is?
Clare: Absolutely. So, myocardial bridging is something that happens in utero. So, at about week 11 to week 12, the coronary arteries are meant to migrate out of the muscle and sit on a nice bed of fat on top of the cardiac muscle. And what you actually get is an incomplete migration of the coronary arteries such that it is still embedded within the muscle and that can be deeply embedded or quite superficially. Now bridging itself probably occurs in about, in some area in your coronary tree in about 30% of people and a lot of the time, it is an incidentaloma. But in a small proportion of people, it is clinically relevant. And that is because you get compression of the coronary artery, not just in systolly, but when it fills in diastolly. And so that can cause ischemia.
Linda: These sound very difficult to diagnose and the particular concern of one of the listeners, is rural GPs who have difficulty in accessing cardiologists. Is there anything extra that a GP might do when thinking of these different kinds of causes for coronary artery disease?
Clare: So, I think the first thing is to take an exceptionally thorough history. And there is a lot in the history. So, in terms of for instance, myocardial bridging, what we see is that people get chest pain with elevated heart rates. So they will get chest pain when they are exerting themselves, but they can also get chest pain with emotional stress, because they become tachycardic. So there is a lot in the history. In terms of things like coronary vasospasm, we talk about early morning chest pain. So, knowing how to take a really nice thorough history is very important. I think it is also important in the first instance to work down the normal pathway of excluding obstructive coronary disease. And then I think there is some reasonable investigations that can be done such as a CT coronary angiogram which will very clearly show myocardial bridging. And the finally, and maybe this is information that I can flick off line because it gets a bit involved, but there are some therapies that we can try for myocardial bridge and for endothelial dysfunction before we go down, you know the very fancy pathways of invasive testing. And they are things like calcium channel blockers, nebivolol and nitrates. Have I confused you more?
Linda: No, no. That is great. Thanks a lot.
Clare: And I am happy to be emailed about those things as well if that is relevant.
So back to awareness. Another big thing is the fact that we know that females are more likely to present with what we call atypical symptoms. But only 26% of women know that a heart attack can present with non-chest pain symptoms. Additionally, only 10% of women who were surveyed knew that hypertension was a risk factor for heart disease. And only 30% of you know, 30 to 65 year olds had had a heart health check. And then in terms of actually knowing their own health, one in three have high cholesterol but 90% were unaware. A quarter over the age of 35 had hypertension and 66% were unaware. A quarter obese, and certainly in many of our populations that would be higher, one in two overweight and one in seven smoke. So you can see, we have got this environment where women have a lot of risk factors. They do not understand their risk factors. They do not understand there relevance to cardiovascular disease and they do not understand what to be worried about or to be aware of. So it is very hard to be your own advocate in a situation like that. So now we have a polling question.
Sammi: Yes, thanks Clare and will just give you 30 seconds to read this, because when we launch the poll you will just be clicking A, B, C, D or E. You will not be able to see the text, so have a read through them now and we will launch that poll.
Clare: So I am so excited because you guys are listening to me and 75% said D, women present later than men with acute coronary syndromes and have more complications. And I think you know, that if that is one of the key take home messages that you take with you, then I think that is brilliant. And the graph there is just again from that study done in Melbourne which just shows exactly the same thing as I said, that in terms of pain to door time and in terms of door to balloon time, women do worse. So that kind of shows us that women are delaying their presentation and then as physicians we are missing something as well.
Jon: Great. So we are going to just change tack a little bit. My name is Jon Hyett. I am an obstetrician. I also work at RPA and we thought we would look at some of the obstetric risk factors that you see that are potentially linked to women developing cardiovascular disease later in life. There is actually quite a lot of epidemiological work that has been done looking at conditions that you see in obstetrics and their relationship to cardiovascular outcomes in later life, specifically to hypertension, to the development of metabolic syndrome and also stroke. So, on the left-hand side of this slide you can see Scandinavian data which looks at maternal mortality and maternal morbidity in women who had preeclampsia. It actually splits these women into different groups and it splits them on the basis of when they developed disease, the severity of that disease typically leading to early delivery. So, on the X axis of both graphs you can see these women are split into groups that delivered either very pre-term or closer to term. And what we see, is that from both the perspective of mortality and also morbidity related to cardiovascular disease, first there is an association with preeclampsia generally, but secondly the earlier you had your preeclampsia, the more likely it is that you will have a cardiovascular complication in later life. So overall in pregnancy, about 7% of women become hypertensive during pregnancy and about 4% to 5% develop preeclampsia. So in other words, one in twenty obstetric patients are going to develop this risk factor for heart disease in later life. And as a consequence, if we know this information and if we know that the majority of women will have a pregnancy at some point in their life, you could argue that this is a useful screening paradigm to use for women when we are looking at risk factors for cardiovascular disease in later life.
On the other side of this slide, you can see some work related to gestational diabetes. So, gestational diabetes is certainly something that we are seeing becoming increasingly prevalent in our population. Here in central Sydney we are now finding about 15% of pregnant women have a diagnosis of gestational diabetes, in fact our antenatal clinic that is specifically for this group of women has become a bit of a cocktail party over the last few years. We find that your overall lifetime risk of type 2 diabetes increases if you had gestational diabetes in your pregnancy and down the bottom of this slide you can just see a meta-analysis, which shows that if you had gestational diabetes, you have about a 1.7 fold increased risk of developing type 2 diabetes in later life and about 50% of women that will develop type 2 diabetes will do that in the first 5 to 10 years after their pregnancy. So, after pregnancy from our perspective, it is quite important that we consider testing for type 2 diabetes in this population. And typically as an obstetrician, I would give women some advice that they should return to their GP and should have a conversation about ongoing screening perhaps on an annual basis to look for type 2 diabetes.
You can see this about the risk following preeclampsia again. It is just some other studies that have reported this, and here just isolates different outcomes and the level of risk that you see. So, if you had preeclampsia, generically you have about a 300 fold increase risk of hypertension, 200 increased risk of ischemic heart disease or of diabetes and a very similar increased level of stroke.
So, if we look at risk factors for both preeclampsia and ischemic heart disease, they are actually very similar. We actually now try to predict your chance of getting preeclampsia in pregnancy. It is something I will come back to you with some more information on later in this talk. But in part we use maternal characteristics for that predictive test. And you can see that there is both some non-modifiable but also some modifiable risk factors that we see in both of these groups. So for example, we know that if women are overweight or if they have chronic hypertension or if they have diabetes, then if we can try to improve the control of these conditions prior to pregnancy, we can potentially improve their pregnancy outcome. But we also see this series of non-modifiable risk factors that are very similar both in patients that develop preeclampsia and those that get ischemic heart disease later in life.
So I wanted to move on to talk about dose response risk. And this is just another epidemiological study that looks at the severity of disease that you get depending on the severity of your adverse pregnancy outcome. So you can see for example, in the purple line that these are women that had preeclampsia. They had a child that was small for gestational age or had intrauterine growth restriction and they delivered pre-term. And this cohort of women are women that really within 10 to 20 years, a very significant proportion of them have developed symptomatic cardiovascular disease.
So the next slide really talks about what it is that causes this change. And this is, if you like, a theoretical process. I am just going to stop for a moment because I think Linda wants to speak.
Linda: Could you just remind us what MACE stands for that is in the previous slide and may appear elsewhere?
Jon: Major adverse cardiovascular event.
Linda: Thank you.
Jon: Do we actually want to just go to some polling questions as well? We could do that before we continue?
Sammi: Yes, absolutely. So we will launch the first poll now. So nice and easy, yes or no one. There we go, we are at 70. So for that first one, I will just quickly share those results with you there and then we will launch another one right now as well. So, if you can answer this one for us now, too.
Jon: So I am going to talk a little bit about if you like the aetiology of these problems that we see in pregnancy. But the link to preeclampsia and ischemic heart disease is potentially related to endothelial dysfunction. There is now a screening test available for preeclampsia that you can offer in the first trimester of pregnancy and I just wanted to highlight that for you, because it is relatively new. Some of the data supporting that was only published last year in the New England Journal of Medicine in about June of last year. So that is the screening test. We will come on to that in a moment. Also, the second part of the poll, all of those agents were things that have been proposed as potential prophylactic treatments against preeclampsia. In fact the best evidence is for aspirin, starting early in pregnancy, by which I mean before 16 weeks of gestation. And meta-analysis shows that if you start aspirin early and continue it through pregnancy, this is low dose aspirin, we use about 150 mg given at night, then you can see up to an 80% to 90% reduction in rates of preeclampsia leading to delivery before 34 weeks gestation.
So just to talk a little bit more about that screening and prophylactic process. We will go back to the main slide deck. And one of the concepts that links pregnancy to vascular disease later in life, is that through your life, you have various endothelial challenges, which gradually increase the risk that you will get cardiovascular disease. So you can see here, in the red line that for a pregnant woman who gets preeclampsia, during her pregnancy you see more endothelial deterioration than you would in someone who does not have that pregnancy complication. And in a healthy population, you can see that after the pregnancy, that individual essentially goes back to baseline and as a consequence you do not see cardiovascular symptoms until relatively late in life. Whereas, for the pregnant woman who gets preeclampsia, we think they have some residual endothelial dysfunction after their pregnancy, that this potentially is worsened with repeated pregnancies and then you can see that they cross a threshold where they are more likely to get cardiovascular disease at an earlier stage of their life.
So just moving on again one slide. We probably know more about preeclampsia now than we have previously. We always had some difficulty understanding the aetiology of this disease. But it seems that there are two major factors involved in the development of preeclampsia. One is the placenta and the other is the maternal endothelium. So early onset preeclampsia primarily seems to be due to an abnormal placenta. Placenta that is not implanted properly. And in that circumstance, the placenta itself becomes ischemic and hypoxic and starts to produce angiogenic factors which are designed to try and improve the local vascularisation of the placenta. But those factors actually will go round the whole of the maternal compartment and consequently cause some endothelial dysfunction as well. That endothelial dysfunction then leads to vasoconstriction and that is where we see some end organ damage and these are the symptoms and signs that we then see as the end stage of this disease process. So, preeclampsia is typically a clinical diagnosis, but fundamentally there has been a whole pathological process underlying this that has different stages. And one of the concepts of first trimester screening for preeclampsia, is that if you could define that placental dysfunction was likely to be a problem and if you could intervene to prevent this at an early stage, then potentially you have a means of preventing the development of clinical symptomatic preeclampsia completely.
So from the screening perspective, we now have a test at 12 weeks that you can do at the same time as the nuchal translucency scan which is traditionally used as part of the chromosomal abnormality screening test. And at that point in time, when you see a mother for an ultrasound at 12 weeks, you can look at blood flow to the placenta by looking at the uterine artery Doppler with the ultrasound. You can put that information together with markers of placental function and in fact they are the same markers that we use for aneuploidy screening. So they are Path A and PLGF and we put those markers together then with maternal blood pressure which you can measure at the same time, and with history, with maternal characteristics to develop a test which actually predicts about 90% of women likely to get preeclampsia before 34 weeks. And importantly, this slide shows that if you give those women aspirin from the time of their 12 week scan through to 26 weeks gestation, you can reduce the prevalence of preeclampsia before 32 weeks which is the point where you will see a significant number of neonatal admissions – you can reduce that by 90%. And for preeclampsia before 27 weeks, again it is very significant, with a reduction of 62%. So certainly I think I would advocate that all women should be offered this screening test if it is available.
So, I think in this section we have talked a bit about how preeclampsia is a risk factor for ongoing cardiovascular disease. We have talked a bit about how we may be able to predict this during the course of pregnancy and indeed potentially prevent this, and we also spoke a bit about the common underlying factor that we see which is one of endothelial dysfunction in these women. I think at this point we have one more poll to run.
Sammi: Yes, we certainly do and we will just give you 30 seconds to read those options of the screen before we launch in for you to select A, B, C, D or E. So have a read of those on your screen. We will give you a couple of seconds to do that.
Jon: So, we think that is great. We agree that preeclampsia is an independent risk factor for cardiovascular disease and we certainly feel that women who are preeclamptic should be recognised as being higher risk in the context of other risk assessments and other prophylactic advice that you would give them to reduce their risk in their future lives. Yes.
Clare: So that is wonderful that 82% thought that preeclampsia was an intendent risk factor, because if nothing else, I hope that that carries into your clinical care if it is not already there and it is certainly not for a lot of cardiologists and when you see a woman at whatever stage in her life and you are assessing her cardiovascular risk which I am going to talk about now, that you will ask her questions about her pregnancy if she has had one, because they are indeed very relevant.
So moving on from what Jon said, but the same theme of gender specific risk factors, I want to briefly touch on hormones. Briefly because it is a very difficult area. But hormonal factors are important. There is some beautiful data that has come out of the UK Biobank. And that is you know, over a million patients. And this is some work by Mark Woodward at the George Institute and it echoes other work that is done, that tells us that reproductive factors are important in the development of cardiovascular disease. And I have just popped up some relative risks for you, or hazard ratios to bring home the point that we do know that early menarche, early menopause and hysterectomy are all associated with an increased risk of cardiovascular disease later in life, particularly hysterectomy and oophorectomy. So we know a surgical menopause is very important as a risk factor for cardiovascular disease.
Moving on to menopause, natural menopause. The data is a little bit more difficult and it is a somewhat controversial area. So if I go back to you know, Professor Mark Woodward, he would tell you that menopause itself, he does not believe is an independent risk factor for cardiovascular disease, but indeed what we are seeing is just advancing female age as a risk factor. If you talk to other people such as Professor Babar or if you look at the WISE data, they would say that they do believe that menopause is an independent risk factor for cardiovascular disease. So, I think that that is still somewhat open to debate. What I would say, is that we do know that there is data that endogenous oestrogen has some cardio-protective features. So we know that oestrogen is important in vasodilatation via a nitric oxide pathway. We know that oestrogen reduces angiotensin converting enzyme. We know that it helps to reduce inflammation and that we have more favourable lipid profiles in the context of endogenous oestrogen. Over there, there is a JAC article that has actually looked at the testosterone oestradiol ratio as being important. So, certainly we know that biochemically things change at menopause. You have an increased LDL as well as increased APoB1 and A1, and increased triglycerides. But I am not sure that I can fully answer the question for you of whether or not menopause itself is an independent risk factor.
I wanted to move on to getting a little bit more practical now and discussing how we assess women at risk, and this is essentially what all of you do every day in your work. So we use multivariable risk calculators. You know ever since the landmark Framingham trial in the 1960s, we have known that we can in the same way as Jon spoke about preeclampsia risk calculators, that we can put a bunch of continuous and categorical variables together and use that to approximate cardiovascular risk in an individual. And this is really important because we know that if we can assign them a risk then it can help to guide in an evidence based fashion, the way that we monitor them and the way that we manage them. So as I have said, most of the currently available risk calculators are at least partially based on Framingham data. The main risk calculator that I suppose is advocated in Australia is the National Vascular Disease Prevention Alliance formulated risk calculator. That predicts a five year risk of a cardiovascular event, and it is endorsed by the National Stroke Foundation, the National Heart Foundation and the Royal Australian College of GPs. So I know that you probably, probably use this every day. And this is what it looks like. So, gender, so are you male or female. What is your age? Systolic blood pressure. Smoking status. Total cholesterol. HDL. Diabetes, yes, no and presence of left ventricular hypertrophy on your ECG. So as I said it is a five year risk predictor. It is only relevant to the 45 to 74 years. So if you have a 38-year-old female that enters your room, you cannot use this calculator except in the Aboriginal and Torres Strait Islander group where we go down to 35. And as I have said, why is it important? Because we do know and we do have quite significant evidence that if you are able to appropriately risk stratify someone, to low or moderate or high risk, then there is evidence about what lifestyle interventions work, what pharmacotherapy is appropriate, what targets you are aiming for, and how intensively you monitor.
So what about these calculators and women? Well unfortunately, they do not do that well. So there have been a lot of studies internationally that have shown that particularly with respect to young females and particularly with respect to non-Caucasian populations, the calculators do not do very well. And what you are probably thinking right now after listening to Jon is, none of them independently account for pregnancy or reproductive factors. So we have just told you that preeclampsia has a relative risk of you know, 200 to 400% of an adverse cardiac event, and then I am telling you that there is no way of accounting for that when you risk stratify women. Now, there was a publication from the early 2000s by Ridker et al where they tried to deal with the fact that a significant proportion of women who have cardiovascular events do not possess these traditional risk factors. They created what is called a Reynolds Risk Score. And I do not know if I can ask Sammi who actually knows about a Reynolds Risk Score? Or Linda? Are we able to just?
Linda: Never heard of it before.
Clare: Never heard of it before. Does anyone else want to…?
Sammi Just type three, yes or no through chat box.
Clare: If they have heard of a Reynolds Risk Score and if indeed they have used a Reynolds Risk Score. No, no, no, no, no never heard of it. Nope. No, no, no. Keeping it interesting with a few nopes. So that does not surprise me. As I say it is a risk score that is focussed on female populations because there is data, there are data that shows that female populations with CVD are more likely to be inflamed, so have more elevated high–sensitivity CRPs. And just to update you, I have got a screen full of no’s. So they proposed two new prediction models, and this has been around for a decade, where they used a composite of inflammatory and lipid biomarkers in addition to our traditional risk factors. And they tested it in female populations such as you know, the Women’s Heart Study and they found that it actually did perform better than traditional risk factors in women, until you put it in a non-white population. So, they then used that risk calculator in a multi-ethnic study of atherosclerosis, the MESA population. And it underestimated risk by about 21%. So we are still not doing too well.
So, this is the Reynolds Risk Score. Down the bottom is where you can find it if you so choose. So it is about predicting future heart attacks, stroke, or other major heart disease over a decade. Again, male or female, age, do you smoke? Yes or no? Systolic blood pressure. Total cholesterol and HDL. And then we had a high-sensitivity CRP and a family history of premature CVD.
Linda: Clare, I can anticipate people will ask about high-sensitivity CRP. I presume that is not the ordinary CRP and we have to request it specifically?
Clare: You do have to request it specifically. It is an HS CRP. Normal is below 0.5. Elevated levels correlate with cardiovascular, adverse cardiovascular outcomes. As we know, inflammation is very important in acute coronary syndrome. I would have to double check, but it is not cheap I do not think. So you know, I do it in a hospital setting.
Linda: Is it Medicare rebatable?
Clare: I believe it is Medicare rebatable but I do not know how much it kind of costs outright and I would have to get back to people on that.
Linda: Okay. Thank you.
Clare: And it is a little bit dependent on your lab as well. There are different reference ranges. But you know, there is very strong literature behind high-sensitivity CRP and its relevance to cardiovascular events. And there was a how do you order it? Oh yes, just HS CRP on a blood form. But the cost, I am not sure about.
This is another risk calculator, just to guild the lily so to speak. This is one that you possibly a lot of you use, which is the US, so ACC American Heart Association Risk Calculator. Based on pooled data, which pulls together many different data sets including Framingham data. But this is representative of about 50% female, again predominantly Caucasian populations. And it is a very similar set of risk factors again that we are seeing.
So, I thought that I would just stop for a second and throw a case out to you. It is a slightly facetious case, but just to drive home a few of the points that we are trying to make. So this is Mrs Risk. She is 45 years old, so she just sneaks into our risk calculators which is just as well because otherwise we would have to just throw our hands up at her. She has had two previous pregnancies, complicated by early onset preeclampsia and Jon has just told you about that, intrauterine growth restriction and gestational diabetes. So she has not had fun in her pregnancies. She has a strong family history of ischemic heart disease with premature ischemic heart disease on her mother’s side of the family. She has PCOS which was diagnosed at the age of 16, which we have not really touched on tonight. She has a BMI of 32. But normal resting blood pressure, at current state of play, normal fasting lipids. She has been told she has impaired glucose tolerance since her pregnancies, but no one has given her a firm diagnosis of diabetes yet. Normal resting ECG and a non-smoker. I do not know if anyone has any great thoughts at that time. We might just dutifully pop her into our, I have chosen our US risk calculator for now, for what that is worth. So as you can see, I will see if I – no sorry, go back. As you can see, if we pop her into our current risk calculators, and we are saying optimal risk is 0.4% over that decade, and she gets a 0.2%. So, Mrs Risk, despite her name, using you know, the internationally recognised you know, American College of Cardiology Risk Factor Calculator, has a 0.2 risk. Optimal cardiovascular risk. So as I have said, this is not gender specific, so we are going to try a bit harder and we are going to pop her into the Reynolds Risk Score, because we know about that now and we think that is really good in females. So again we pop in her details. She does not smoke. She is female. She is 45. As we said, her cholesterol looks okay at the moment. Now I have given her a high-sensitivity CRP of 3.5, and that is actually very elevated. And the reason that I have done that, is because in current data that Jon and I are working on, after preeclampsia, we know these women are inflamed. So, I am seeing high-sensitivity CRPs that are around the 3.5. So I pop that in to be fair, and as you can see, her 10 year risk of having a major cardiac event is 1%. Does anyone have any thoughts on that? Someone has written, does she have any cardiac symptoms? So, I should actually clarify that point. These are not really, these risk calculators are primary preventative risk calculators. So they are not for people with coronary disease and they are not for people with active cardiovascular symptoms. This is about risk stratifying people and working out how we best monitor them and intervene on their modifiable risk factors. So, do we think her risk prediction is accurate? So someone has actually written an interesting thing, which is “I think she would have an elevated risk beyond a decade.” And that is actually a really interesting point. For two reasons. One is the fact that what I think they are trying to say to me, is that in a young population, having a short term risk calculator might not be relevant, and that is true. But what we know about preeclampsia from work that Jon has done, and has been done by Annemarie Hennessy as well, is that preeclampsia is a risk for premature cardiovascular disease. So we are not talking about cardiovascular disease when you are 70, we are talking about cardiovascular disease a decade after your preeclampsia. So, the point that we are not looking for a long enough period I do not think is true. Jon would you agree?
Jon: Yes. I mean I think it, look there are two sides to this argument. I think that what we are seeing with preeclampsia is women that get early cardiovascular disease and it is not described in these calculators. I think that that is what we would want a take home message to be, that you know, these risk calculators are only of limited value for this particular population. And it is probably more important just to recognise that these women had severe early onset preeclampsia and recognise that that is a risk factor per se rather than to then try and shoe horn them into a calculator that does not actually include that as a risk assessment process. It is probably true these women also have a higher risk at the age of 70, but certainly the fact that they get a 10 year score that does not include their preeclampsia is really of no value to them.
Clare: But I certainly would say the take home message is that they are at risk of premature cardiovascular disease and we have data, local data supporting that. So it is not okay to send those people away and think, we will think about it in 20 years. We need to be thinking about it in the post-partum setting and in that five to ten years post-partum it is actually very relevant.
I have asked the question, what in your history are you worried about and I will tell you what I am worried about. I am worried about her preeclampsia. I am certainly worried about her IUGR as Jon said, that has an additional risk. I am worried about her pre-term birth. That is kind of the triple whammy. And then you add gestational diabetes and you know, her risk is really very significant and I mean, there is a study called the CHAMPS study of over one million women, and you know it is not contemporary data it is old data, but it shows when you out these risk factors together, if you add metabolic syndrome, some of those cohorts had up to a 12 fold increase risk. So there is a synergy in the risk. PCOS is difficult and I do not want to get into it too much, but certainly there is emerging data particularly around the issue of impaired glucose tolerance that these women are at elevated cardiovascular risk. As we know, impaired glucose tolerance is a risk, even though it does not fit into our calculator. Premature CVD and obesity. Both risk factors. So to me, if I saw this woman, she would be someone I would be following very closely.
So, where does that lead us? I have just kind of ruined everything that you thought that you know, that you would do when someone walked into your offices and what we are going to do practically speaking? Well, I will answer that, but I just, before we do that, so this is just a little bit of a take home slide in terms of barriers to improving cardiovascular outcomes for women, in terms of lack of research, the lack of gender specific risk factors and that translational gap from what happens in pregnancy to getting to a cardiologist or getting to a general practitioner for a heart health check, and the poor performance of our risk calculators. But that is a bit of a take home slide.
So, let’s get practical in our last couple of minutes. So, general advice. What can we do? Well the general advice is the advice that you give everyone that you are worried about from a cardiovascular perspective. So, maintaining a healthy weight, a healthy diet, engaging in regular physical activity, not smoking, regular blood pressure reviews, regular cholesterol reviews, regular blood glucose reviews, following the guidelines of OGTTs if they have indeed had a metabolic complication during their pregnancy and planning their subsequent pregnancies. And in terms of subsequent pregnancies, just to flag the fact that women are at increased risk of preeclampsia if they have suffered from preeclampsia and the data seems to be a relative risk of over 7. Jon, I do not know if you want to talk any more on that at the moment with our flagging time?
Jon: I do not think so.
Clare: Okay. So, what does this mean to your work? What are you going to take home to how you manage your patients, if indeed you take home anything and I hope you do. The first is, just because I have talked about the limitations, please do assess a woman’s cardiovascular risk. It is very important. Put it on your radar for every woman that you see and put it on their radar. And then if it is a young woman who comes to see you, understand the limitations of your risk calculator. Understand that it does not tell you the full story in terms of their risk. Sure, use it. But then also use the knowledge you have gained tonight about risk factors that are not accounted for. Think and enquire broadly. So think about these other conditions I said, we know that women are more likely to have non-obstructive coronary disease and to have these other conditions and keep them in the back of your mind. Never discount coronary disease or heart disease because you are looking at a female or because they are young. When you are risk assessing someone now, ask them about smoking. Ask them about diabetes. Ask them about family history. Ask them about hypertension and lipids and then please do ask them about their pregnancy experience. Ask them about the hypertensive and metabolic disorders of pregnancy. And then understand its relevance. And then in those that you identify at high risk with those special flags, follow them closely. Their blood pressure might be normal. Their lipids might be normal, but it may not be you know in a year or two’s time. And educate your women. So let them know what you are worried about. Let them know that they have cardiovascular risks.
This is just a quick slide that I will not flag on too much, just saying that you know, I have talked about lifestyle intervention. We all know it is very difficult. The Get Healthy service is out there and you may find that it is of benefit in some of your patients. It is evidence based and it is free, and it is a telephone based health coaching.
And just with the last couple of minutes, I might just talk about this piece of information which is on the Heart Foundation website and was created in conjunction with the Heart Foundation, and Linda and Jon and myself have all played a role in this. And this was about the fact that we are now putting it back to general practitioners and saying we are worried these women who have had a hypertensive disorder of pregnancy can you please see them? And then we are not really giving you any tools to really do that. So this is just some simple information on the Heart Foundation website which talks about what we think the link is between these disorders of pregnancy and cardiovascular disease. The approximate risk, understanding the fact that every pregnancy is different and every profile is different. Women that we want you to follow more closely, so the early onset, the concomitant metabolic syndromes, the recurrent preeclampsia or the ones who gave birth to very small babies or very early. And then some practical tips for how you can manage these people and the things to do when. And just a caveat, that lipids are very hard to assess when a woman is breast feeding and certainly in the early post-partum period, and so I only really recommend doing fasting lipids at about 12 months post-partum. Before that it will be elevated and it will not be indicative of their long term lipid profile.
These information documents are new. We have not received feedback on them. So I would be very keen to hear if anyone thinks that they are of value, not of value, too much, too little, you know we would very much like to hear about that.
Sammi: Yes, we might send a question about that in our follow up email when we send you all the resources and the presentation. So if you could keep an eye out for that and send us your feedback specifically on that slide, that would be great.
Linda: So I hope after this very interactive and quite stimulating presentation, you do feel that you have been exposed to a summary of the current evidence base, you understand the relationship between hypertensive and metabolic complications in pregnancy and cardiovascular risk. It is interesting the variance in the risk calculators and the concern that was raised, should still allow us to use the evidence that we have got and whatever tools we do have to appropriately advise and manage female patients in relation to cardiovascular risk. And we can deliver care that reflects current sex-specific differences in the pathogenesis presentation management and outcomes of cardiovascular disease. Thanks a lot Clare and Jon.
Jon: Pleasure. Thank you for having us.
Sammi: That is great. Thank you, Linda, Clare and Jon and everybody on line who has joined us tonight. We hope we have answered all your questions. Thank you again to our presenters and thank you to everybody on line, we hope you enjoy the rest of your night.