Ep66: Gendered Medicine 1- Heart Disease

Ep66: Gendered Medicine 1- Heart Disease
Date:
17 January 2021
Category:

Fellows of the RACP can claim CPD credits via MyCPD for listening to this episode and reading the resources below.

We traditionally think of cardiovascular disease as a man’s problem, but it’s the leading cause of death for women as well as men in most of the industrialized world. Despite great advances in the management of heart disease in recent years, women are still not getting the same quality of care as men. Readmissions and mortality following an acute myocardial infarction at least two times higher in women as they are in men.

Put simply, cardiovascular disease is better understood in men, the presentations and diagnosis occur more promptly, and therapies are more consistently delivered to male patients. In this episode we explore the subtle biases at every stage that nudge male and female patients down different health pathways and result in gendered health outcomes.

Credits

Guest
Associate Professor Sarah Zaman FRACP (Westmead Hospital, University of Sydney)

Production
Written and produced by Mic Cavazzini DPhil. Music licenced from Epidemic Sound includes ‘Dew’ and ‘Vargtimmen’ by Da Sein, ‘Spring’ by Cora Zea, ‘Missing Memories’ by Christopher Moe Ditlevsen and ‘Feels Like I’m Going Crazy’ by Tigeblood Jewel. Image licenced from Getty Images.

Editorial feedback for this episode was kindly provided by physicians of the RACP’s Podcast Editorial Group; Sern Wei Yeoh, Joseph Lee, Phillipa Wormald, Rhiannon Mellor,  Seema Radhakrishnan, Atif Mohammed Slim and Li-Sza Tan.

References

Caroline Criado Perez at Engage 19 [Engage 19, IAB UK]
The deadly truth about a world built for men [Caroline Criado Perez, The Guardian]
Sex Disparities in Myocardial Infarction: Biology or Bias? [Hear Lung Circ 2020, Zaman]
Comparison of Late Cardiac Death and Myocardial Infarction Rates in Women Vs Men With ST-Elevation Myocardial Infarction [American Journal of Cardiology 2020 Burgess, Zaman]
Implicit Gender Bias and the Use of Cardiovascular Tests Among Cardiologists [JAHA 2017]
Preventing and Experiencing Ischemic Heart Disease as a Woman: State of the Science [Circulation 2016]
Sex/Gender Differences in Cardiovascular Disease Prevention: What a Difference a Decade Makes [Circulation 2011]
Gender inequalities in cardiovascular risk factor assessment and management in primary healthcare [2017 Heart, Hyun] Editorial: Gender disparities in cardiovascular disease prevention
Cardiovascular Disease and the Female Disadvantage [2019, Int J Environ Res Public Health, Woodward]
Preventing and experiencing ischemic heart disease as a woman: state of the science [Circulation 2016]
Implicit Gender Bias and the Use of Cardiovascular Tests Among Cardiologists  [JAHA 2017]
Comparison of Late Cardiac Death and Myocardial Infarction Rates in Women Vs Men With ST-Elevation Myocardial Infarction [American Journal of Cardiology 2020 Burgess, Zaman] Editorial: Gender Matters in Biological Research and Medical Practice
Sex and gender in health research: updating policy to reflect evidence [MJA]
Does sex predict quality of life after acute coronary syndromes: an Australian, state-wide, multicentre prospective cohort study [BMJ]
Symptom recognition and healthcare experiences of young women with acute myocardial infarction [Circulation]
Trends and comparison of female first authorship in high impact medical journals: observational study (1994-2014) [BMJ]
Acute Myocardial Infarction in Women  [Circulation]
How Does Mental Health Impact Women's Heart Health? [Heart Lung Circulation]
Sex differences in the association between marital status and the risk of cardiovascular, cancer, and all-cause mortality: a systematic review and meta-analysis of 7,881,040 individuals [BMC]
Opinion: Gender diversity leads to better science [PNAS]

Transcript

MIC CAVAZZINI:               Architecture and industrial design are focused on making interactions between humans and the built environment as seamless as possible. You can see this most overtly in car design where a mannequin in an orange jumpsuit takes the place of the future driver and passengers.

Since the 1970s, that crash test dummy has been around 175 centimetres tall and 76kg in weight. The shape and position of the seat, the angles to the pedals and the lines of sight are perfectly laid out. Except that this dummy doesn’t represent the average person. It has the proportions of a man in 50th percentile, right down to the distribution of muscle-mass.

Little wonder, therefore, that women are 73% more likely to suffer serious injury from a front-on car crash. They’re too close to the wheel, they’re sitting too upright, and the seatback doesn’t absorb the whiplash for their lighter torsos. These design flaws have been known since the 1980s, but regulators still don’t mandate use of an anthropometrically accurate female model in any of their tests. At best, car manufacturers used the same dummies just scaled down by 70% in size.

The same bias towards a masculine default explains why female pianists suffer hand strain more often than men while struggling to crack the virtuoso rankings. Or why there’s always a queue outside the women’s toilets at theatre intermission. It’s not so much a case of “one size fits all” as “one size fits men.”

These stories are described in a fascinating book called Invisible Women, by British writer and campaigner Caroline Criado Perez. They’re pretty clear-cut demonstrations of gender bias with obvious solutions, but there was another case study that was thought-provoking in its subtlety.

In 2011 the city council of Karlskoga in Sweden was being asked to meet certain gender equality targets, and one disgruntled officer laughed that at least “the gender people” would keep their noses out of the snow clearing department- there’s no possible way that this could be biased, right? So “the gender people” took a closer look. Here’s Caroline Criado Perez herself, speaking at the Engage 19 conference

CAROLINE CRIADO PEREZ:            So the way they had always done snow clearing done in the past, and the way it is still done in a lot of countries and cities around the world, is to clear the major roads first and only then move on to the local roads and the pavements. But it turns out this is biased towards male travel patterns. So men and women tend to travel in different ways. Men tend to travel in a much more simple way – a twice daily commute in and out of work driving a car. Women – both because they tend to have less money than men and also because even when a household has a car men tend to dominate access to it – women are more likely to use public transport and they have more complicated travel patterns because of their unpaid care work. They have to for example drop the kids off at school before going in to work, pick up the groceries on the way home, maybe drop in on an elderly relative.

So they do this thing called “trip chaining” – lots of short, interconnected trips into suburbs not necessarily in a straight line. So they decided: “Well we’ll switch it” – because they figured it wouldn’t cost them any more money and after all it’s probably harder to push a buggy through three inches of snow than to drive a car slowly through three inches of snow. It turned out that the admissions to A&E during the winter months fell significantly because actually they were right – it was harder to push a buggy through three inches of snow, and it wasn’t the men who were turning up at A&E having crashed in the snow. It was women turning up having fractured their bones by falling over on the icy conditions. The cost of A&E in the winter months was three times the cost of the winter road maintenance. So the moral of the story is sexism doesn’t have to be deliberate and feminism saves you money.

MIC CAVAZZINI:               This story sent me looking for examples of this in medicine, of structural biases unwittingly leading to gendered outcomes. Because this is a podcast about the culture of medicine. Welcome to Pomegranate Health from the Royal Australasian College of Physicians. I’m Mic Cavazzini.

There are some areas of medicine where gender is a central feature and a hotly debated one; the poor understanding of pain disorders in women is one example we’ll discuss these in the next episode. Today I want to look at a less obvious area that has very lethal consequences; cardiovascular health. Both women and men have hearts, after all, and both get heart disease. So why do women die at much higher rates from it?

Some of the trend is because women develop cardiovascular disease in later frailer years. But that’s only part of the story- if you just focus on acute myocardial infarction in the under 65 age group, 30 day readmissions and mortality are twice as high in women as in men.

We traditionally think of cardiovascular disease as a man’s problem, but it’s the leading cause of death for women as well in most of the industrialized world. Despite great advances in the management of heart disease in recent years, women are still not getting the same quality of care as men. In a 2018 study of English and Welsh inpatient records spanning a decade, researchers estimated that about 8200 out of 28 000 deaths could have been averted had there not been a gender discrepancy in almost every quality indicator.

Put simply, cardiovascular disease is better understood in men, the presentations and diagnosis occur more promptly, and therapies are more consistently delivered to male patients. To explain further, I spoke to Associate Professor Sarah Zaman. You might also hear the summer chorus of Sydney’s cicadas in the background.

SARAH ZAMAN:               I’m Sarah Zaman. I’m an Associate Professor at the University of Sydney. And then I’m also an interventional cardiologist at Westmead Hospital where I practice in the cath lab doing procedures and as a cardiologist looking after patients.

MIC CAVAZZINI:               You made my job very easy with your recent review titled “Sex Disparities in Myocardial Infarction: Biology or Bias?”. I’m going to start in the middle of your story, in the emergency room setting. What’s the experience of women in the waiting room? Do they still wait minutes longer than men to be seen, as was found in a 1998 study in southwestern Sydney hospitals?

SARAH ZAMAN:               Yeah I am in touch with another emergency nurse who’s an academic and a researcher and she is looking at women and chest pain and there’s issues after the come into the emergency and what happens afterwards. So they’re less likely to get referred to see a cardiologist or a specialist despite presenting with cardiac like symptoms. So there is some discrepancy there but I guess the real issue that I focused on is those who actually consequently have heart attacks because that’s where time is muscle.

MIC CAVAZZINI:               There’s an influential review from 2004 by US cardiologist Professor Nanette Wenger who wrote that women were seven times more likely than men to be misdiagnosed in the middle of having a heart attack. And there are more current anecdotes of women being discharged with antacids to treat indigestion rather than having the heart condition diagnosed. Apart from the quote-unquote “typical” presentations, what are the symptoms that should be recognised in women?

SARAH ZAMAN:               Well I still think that a lot of this discussion about atypical presentations in men versus women, a lot of that is a bias as well. So we know that in younger women, particularly with a heart attack, they have equal amounts of chest pain as men – so we’re talking 90% of them have chest pain. And as a cardiologist treating these patients, even a lot of men will have what we would say the lack of the classical symptoms. So I think calling things atypical in this day and age isn’t correct anymore, and I think if someone has chest pain then you consider them for a heart attack.

I guess the other thing to draw on that is that women are more likely to have associated features. So women are more likely than men in several studies now to have things like jaw pain, backache, nausea, dizziness, vomiting, etc. And this can sort of sway the health practitioner away from the true diagnosis of MI, or myocardial infarction, but they’re still just as likely as men, particularly the younger cohort, to have chest pain as well.

MIC CAVAZZINI:               But women are more likely to have the right coronary artery occluded rather than the canonical left anterior, which is even referred to as the “widow-maker.” Would that be so canonical if heart disease had been studied more extensively in women?

SARAH ZAMAN:               Yeah, I mean they still are very likely to have the left anterior descending, obviously the most important artery occluded, but just slightly higher rates of right coronary artery occlusion in an acute form of a heart attack in women versus men. But it’s not a huge difference and it wouldn’t account for all the different delays that we’re seeing in women versus men. But of course, if your right coronary artery is occluded your ECG findings can be a little bit more subtle. And once again if you’ve already got a bias whereby you think women are lower risk and you’ve got subtle ECG findings it compounds the issue.

MIC CAVAZZINI:               Yeah as you’ve said, on an electrocardiogram the ST elevation is actually less prominent in women and more easily missed. Is that just the way things are or is that the way the tool has been developed? You know, could the sensitivity in women be improved with different placement of leads or specialised detection algorithms?

SARAH ZAMAN:               Probably not with different placement of leads, but we do have protocols that are inbuilt into a lot of the ECG machines and obviously if the machine recognises it – and I’m not saying it’s always perfect – but it should trigger you as the treating doctor to actually consider that.

MIC CAVAZZINI:               And you’ve written that not just ECG but every diagnostic test for MI is affected by sex. Indeed, myocardial damage causes relatively lower levels of circulating troponin in women than in men. In a British RCT from last year the standard test was blind to 29% of women with myocardial damage. By comparison only 6% of the male patients were reclassified through a high sensitivity assay with sex-specific thresholds.

SARAH ZAMAN:               I mean it’s a complex field because now we’re talking different types of troponin assays and there’s high sensitivity troponin which the majority of institutions in Australia would use now. Whereas the previous troponin assay was not very sensitive and a lot of smaller MIs could be missed. But it just goes to show that we should be using high sensitivity troponins and yes, I think we should have sex-specific troponin cut-offs, but once again it becomes complex because everyone uses a different troponin assay. You can’t give a generic cut-off for women versus men so it’s really just a guideline recommendation that each institution should actually look at that assay and know what the sex-specific cut-offs are.

MIC CAVAZZINI:               And another bias in the diagnostic process, female patients with suspected non-STEMI undergo angiography less often than men. Although you’ve written that this might be explainable because it has less diagnostic yield in women. Is that a rational justification?

SARAH ZAMAN:               Not really because you should only say it has less diagnostic yield once you’ve done the diagnostic test.

MIC CAVAZZINI:               Well that’s the argument that’s given – is that right?

SARAH ZAMAN:               Well I think probably the first argument that’s given for not doing an invasive coronary angiogram on all non-STEMIs, particularly women, is that if they’re older age or have higher comorbidities. So we know that women with heart attacks are older, they’re more likely to be diabetic, have other comorbidities. And of course, it then becomes a clinical decision as to if you do an invasive test that does have risk involved and it may not change the long-term prognosis. Saying that, a lot of these patients do still benefit. So even patients in their 80s with comorbidities might have a big benefit from having a diagnostic test determining what degree of coronary disease they have and that then is the driver of starting a lot of our medical therapies. In non-STEMIs I think the main concern is that they’re not getting the invasive test in the first place, so if you miss all those steps you can miss a lot of the treatment that would improve that patient’s long-term prognosis, even if they do have comorbidities.

MIC CAVAZZINI:               The whole pathway is altered.

SARAH ZAMAN:               Yeah. So there’s definitely a degree of bias that still exists in that cohort as well.

MIC CAVAZZINI:               I hope you can see that that when we’re talking about gender bias, we don’t mean overt sexism and nor are we pointing the finger at any doctors in particular. We’re talking about forces woven into healthcare and society more broadly, that nudge male and female patients down different paths and result in these gendered health outcomes. The word gender is used in this context because it refers to the way people are treated.

In that sense, some of the experiences described will be familiar to people who haven’t always lived life as a women or who don’t identify with the gender binary. They often have to contend with inequities on top of the ones we’re discussing today, and that’s true of course, for people from certain ethnic or socio-economic groups too. There isn’t the scope in this podcast to elaborate on all these experiences specifically, but I hope this is a useful conversation starter about any unwarranted variation in delivery of health services.

And there is some evidence that implicit bias can be counteracted in clinical practice.  In a 2017 survey, American cardiologists were on average more likely to rate angiography as having “high” utility in simulated male patients compared to women and a key finding was that this was more prominent for those clinicians who scored highly for implicit gender bias in a word association test.

But that implicit bias score did not affect recommendations for angiography in patients who had abnormal results from an exercise treadmill test. This suggests that very clear protocol-driven processes can override other tendencies.

However, even when women are definitively diagnosed with a myocardial infarction, there is hesitation to give them invasive testing and treatment. That was true in the British study mentioned earlier, and also findings from Sweden and Australia. In the CONCORDANCE study, 2900 admission records from 41 Australian hospitals were analysed, and it was found that women were half as likely as men to receive any guideline-recommended intervention for MI. The biggest gender difference was for revascularisation with an odds ratio of 0.42 and the smallest difference was for primary percutaneous coronary intervention at 0.76. Sarah Zaman explains some of the thinking that might lead to differences in treatment rates.

SARAH ZAMAN:               Well I mean it’s interesting then in that study when you’re talking primary PCI, so that’s someone who’s having an ST elevation MI where really we know they should go straight for an emergency coronary angiogram. It makes sense that they have lower rates of PCI or stenting because women do tend to have less obstructive coronary artery disease. But I think the bigger concern is that they’re not getting the diagnostic test in the first place.

MIC CAVAZZINI:               You’re less worried about there may be a good judgement that was made in the lack of intervention whereas …

SARAH ZAMAN:               Yeah, exactly. Because if they have less obstructive coronary artery disease you’re less likely to put in a stent, but that doesn’t preclude them from receiving optimal medical management. They should still receive all the right medications.

MIC CAVAZZINI:               The confound you’ve mentioned about women being older was found in that study and higher rates of comorbidity, but you wrote in your review that there also is a perception that women are at higher risk of bleeding. Is that a fact or is it just a trope of the frailer sex?

SARAH ZAMAN:               No, it is a fact. I mean women do have higher rates of bleeding after heart attacks and we think that we shouldn’t give them some of these more potent blood thinners. So obviously we give them dual anti platelet therapy, aspirin, Ticagrelor or Plavix, but often we don’t give other things like intravenous Heparin or Clexane or some stronger blood thinners that you can give in the cath lab, particularly in the setting of acute STEMI because we do see them to be at higher risk. And part of that is true – so if we adjust for confounders women with heart attacks do tend to bleed more than men but the other thing is that the medications that we give, obviously they’ve been tested in large clinical trials of predominately male participants. So who knows if the drugs that we’re giving at the doses that we’re giving are actually the right doses for women who of course have smaller body sizes, smaller body surface area? But it’s sort of one treatment fits all.

MIC CAVAZZINI:               I think I read that even with higher rates of complications the overall benefits are still there.

SARAH ZAMAN:               Absolutely, yeah.

MIC CAVAZZINI:               It might just be a different kind of bias in practice that you don’t want to harm the patient.

SARAH ZAMAN:               Exactly, yeah.

MIC CAVAZZINI:               In your most recent paper you took patients who’d undergone PCI and quantified the effectiveness of reperfusion using angiography. Have I understood that right?

SARAH ZAMAN:               Yeah I think so. So we’re talking about the fact that often when a patient comes in with a heart attack they’ll have a blocked vessel and we treat the blocked vessel. And that usually has a really high success rate. Like I said, more than 95% has an open artery at the end – good flow, good result, from the actual procedure. That doesn’t mean they’re necessarily going to do well. And then a lot of those patients have residual disease, so they’ve got coronary artery blockages or plaque in other arteries that didn’t actually cause the heart attack. Usually you fix it during that patient’s admission. But that Australian study, Dr Sonya Burgess was the lead author on that one, so that one showed that women were much less likely to have these other non-culprit arteries fixed as compared to men. So we’re not giving them complete revascularisation which we know is really important for their long-term prognosis.

MIC CAVAZZINI:               There are differences in cardiovascular pathology that may have more to do with sex than with gender. In Sarah Zaman’s review she notes that myocardial infarction in the absence of obstructive stenosis is five times more common in women than in men. In younger women particularly, MI is associated with plaque erosion rather than plaque rupture and also higher rates of coronary artery dissection, which is a spontaneous tearing of blood vessels. Microvascular causes are also more common in women including microvascular spasm, Takotsubo syndrome and myocarditis.

But there’s a lot about female physiology and disease that isn’t as well understood because we just haven’t been looking. As Professor Nanette Wenger wrote in a 2004 call to arms; “For many years, the medical community has viewed women’s health with a bikini approach, focusing essentially on the breast and reproductive system. The rest of the woman was virtually ignored in considerations of women’s health; the tacit assumption was that women and men reacted comparably to diseases and drugs.” End quote.

Some of the most influential studies in cardiovascular health completely overlooked female patients. Take the Physician’s Health Study that in 1989 concluded that daily aspirin reduced the risk of myocardial infarction- that was conducted on 22,071 men but no women. Similarly the 1982 Multiple Risk Factor Intervention Trial.

Now it’s true that for many years there were policies that actively excluded women of childbearing potential from drug trials, but this might be forgivable given it was a response to the thalidomide tragedy of the 1960s. I guess the paternalistic part is that weren’t even asked whether they were trying to get pregnant. Of course by excluding women from clinical research, the chance of drug complications would become more likely. Nanette Wenger noted how 8 of the 10 prescription drugs withdrawn from the market between 1997 and 2003 caused more side-effects in women than in men.

One notable gender-medication gap is in drugs is for heart failure. Existing drugs are more effective for heart failure with reduced ejection fraction and this is more typical in male patients. Women who develop heart failure are more likely to maintain ejection fraction, but there isn’t much to offer them the way of pharmacological therapy. This may explain the fact that women are more likely to get hospitalised and die from this condition than men. I asked Sarah Zaman if this availability of drug was a result of gender bias in research, or was it just the luck of the draw- that the right molecules hadn’t fallen out for the female pathology.

SARAH ZAMAN:               No I think this actually – it is a bias in where our research has been focused in certainly the cardiovascular arena. And I think it’s only in the last decade where we’ve got a lot of people dedicated to women’s heart disease research and looking at these different sex differences that we really have come to recognise this – that women are more likely to have heart failure with preserved ejection fraction. And unfortunately that is the cohort that we appear to have almost no effective treatments for, and I don’t think that that’s a coincidence. That recent paper in The Lancet looked at all those heart failure medications and it seems almost outrageous to do a paper 20 years after we’ve instigated all these therapies that shows that the doses that we give our men and our women – previously we’d say up titrate ACE inhibitors, beta blockers, to the maximum tolerated dose in the presence of heart failure. But in fact you only need to titrate to half the dose to achieve the exact same effect in a woman as you would in a man. And we discovered that a year ago even though we’ve been using these drugs for two decades.

MIC CAVAZZINI:               Yeah, so drug trials have classically recruited men more than women but from the nineties you did start to see a requirement from the NIH in America to recruit more women, but the conversation is still ongoing. In a special edition of the journal Circulation from last year, researchers looked at the 740 trials for cardiovascular health completed between 2010 and 2017. From a total of 850,000 participants 38% were women. So is it a conversation that is had in the research environments that you work in?

SARAH ZAMAN:               Yeah, absolutely. I mean at most conferences now we do talk about how we recruit more female participants particularly to our cardiovascular trials. Now of course there are some caveats to that because it depends – you want to represent the patient population that you’re treating, so you want to recruit that proportion. So if you’re talking an acute heart attack or a STEMI you’re probably only going to recruit 25% female. But it should be that 25%, not that 5 to 10%. But if you’re looking at conditions like heart failure really there should be equal representation of men and women, but I think it’s an ongoing conversation because we still don’t do it that well. And even if it is a trial that does affect predominantly men – so just say you did only have 25% female participants, naturally, based on the disease proportions. But you still need to ensure that you recruit enough women to do sex-specific analyses, and that should be put into your sample size calculations.

MIC CAVAZZINI:               I have to mention the findings of a 2018 study from Proceedings of the National Academy of Sciences in which researchers performed a census of almost 600,000 MI-related admissions to EDs in Florida over two decades. Consistent with the trends we’ve already described, female patients were shown have a lower probability of surviving treatment than men by about 1%, but only when their cardiologist was a man. For female cardiologists there was no gender difference in patient outcomes. What changes when both the doctor and the patient are women?

SARAH ZAMAN:               Yeah, I mean this is a study that certainly has been very controversial and I have been asked about this study a lot, because of course you can’t exclude – there’s always going to be confounders in a large observational study like this. But still, I think it’s a pertinent finding and it should trigger you to look at your workforce. And this finding actually has been replicated in other specialties as well, so there are some studies to show that female gastroenterologists for instance are more likely to pick up adenomas and a few different sex differences in terms of the profession. But I think it actually highlights a critical issue in cardiology in that our workforce is by no means representative of our patient population. So in cardiology we’re talking 15% female cardiologists and in interventional cardiology, which is where I practice, it’s less than 5%. And the problem is if you’re a female patient who wants to be treated by a female doctor then it’s very difficult to find someone, and I think that does propagate some of these biases.

MIC CAVAZZINI:               We already discussed the gender gap in the medical profession back in episode 16. I’ll just add some comments from an opinion piece in PNAS which makes the point that greater diversity in the profession helps eliminate blind spots in research design. Currently the proportion of women among first authors in the main medical journals is only about 30% and this glass ceiling was reached over a decade ago.

On top of the under-representation of female participants in clinical trials, as far back as 1994 the NIH has also asked that primary research outcomes be stratified by sex so that clinical decisions could be better informed. But this is still an issue even to this day, as demonstrated in an audit of all 200 citations that informed the current Australian guidelines for management of acute coronary syndrome.  Only 18% of papers report sex-disaggregated results and 30% of publications don’t even mention “sex” or “gender” in the text at all. The researchers from the George Institute in Sydney have since published a checklist for academics designing and writing up future research papers.

To go back to hospital management for a moment. The story doesn’t end at inequitable rates of diagnostic angiography, or interventional medicine. There are even discrepancies in the prescription of guideline-recommended preventative medicines. In the CONCORDANCE study, for example, women discharged from Australian hospitals after having experienced a STEMI were half as likely to receive statin therapy as men. It’s not clear whether cardiologists always have a rational explanation for this.

SARAH ZAMAN:               Well some of it can be explained. So I think we can explain some of it by the fact that women are more likely to have some of these other non-coronary artery disease causes of a heart attack. And so in these situations perhaps statins aren’t indicated, particularly in SCAD and Takotsubos, you wouldn’t give statins. But that’s really the minority so it does not explain by any means that huge discrepancy that we’re seeing.

Some other people might argue that women get more side effects from statins and therefore it gets stopped down the track, but once again we’re talking only about 5% of women who have statin side effects. So a lot of that still has to be this unexplained bias where women are perceived to be at lower risk despite having a diagnosed heart attack and perhaps aren’t all getting prescribed the statin.

MIC CAVAZZINI:               The gender differences for prescribing beta blockers or ACE inhibitors/angiotensin receptor blockers or a second anti platelet drug were not quite as bad. But even aspirin was given less frequently to female patients and women are referred for cardiac rehabilitation three-quarters as often as men.

SARAH ZAMAN:               Yeah, which further compounds the problem because when you attend cardiac rehab of course it comes with an education program and that would then improve adherence to a lot of these medications. So if you’re less likely to attend – do the exercise and education program – you’re probably less likely to be adherent to your medications as well.

MIC CAVAZZINI:               People might say of women or other minority patients: “Well they don’t go to cardiac rehab when I refer them.” But you ask in your review, “how easy is it for patients to get there? Is the rehab tailored to their abilities or interests?”

SARAH ZAMAN:               Of course part of that is the rehab programs. It is one size fits all in a lot of centres and of course if you’re the only female in a room full of middle aged or older males you might be deterred from attending. There are a lot of programs now and research studies ongoing that are looking at, you know, different female focused rehab programs like incorporating yoga and other aspects that might appeal more to women. But the issue of being able to attend because it’s during weekdays or working hours, that can be a deterrent to both men and women, and so we do try and tailor programs after hours as well. But I think for the women who are mothers, so the younger cohort of women, often they’re balancing work, plus family, plus kids – and unfortunately a lot of that in today’s society still falls to the woman.

MIC CAVAZZINI:               There have been women-specific guidelines and training unrolled over the years in the UK and the US. I read somewhere that the impact has been underwhelming. Like we said, there are so many little biases at every step of the pathway. Do you need something like a women-specific cardiology clinic just to sweep all of those out of the way?

SARAH ZAMAN:               Well I think the jury’s still out a little bit on that. So if you look at the US they actually do have a lot of focused clinics that look at non-traditional risk factors and that also treat some of these very female predominant heart conditions. But we don’t tend to have that in Australia. So the only women’s heart clinics that currently exist is set up at Royal Prince Alfred Hospital and The Alfred – so there’s two cardiologists that have worked hard to set up those clinics. But in reality without a funding model, without it being multidisciplinary, the effect isn’t going to be as great. And the other issue is that once again they’re always based in tertiary teaching hospitals, so it’s never going to get away from the fact that those out in more isolated geographical locations or from perhaps minority ethnic backgrounds or non-English speaking backgrounds, are still much less likely to access those clinics. So I think that wouldn’t solve the problem completely.

MIC CAVAZZINI:               Well I wasn’t suggesting that, but I was wondering if the biases are so ingrained that only with a shiny new building with staff that are trained from scratch can you …

SARAH ZAMAN:               Well I think it helps because it’s that whole education process that goes downstream as well. So if you set up this state of the art women’s heart clinic – it’s multidisciplinary, it gets recognised as a true division that needs to be focused on – then there’s always downstream effects. Because then it leads to more education, it leads to more collaboration, and then people recognise that it’s such a major issue that you need to dedicate the service to it.

MIC CAVAZZINI:               To reference the Australian CONCORDANCE study once more, there’s a staggering difference in outcomes of men and women over the 6 months following an ST-elevation myocardial infarction. Women are almost three times more likely than men to have experienced another major adverse cardiovascular event and more than twice as likely to have died from it. But discrepancies in inpatient care are only part of the story.

In a 2019 paper in JAMA, Sarah Zaman and colleagues quantified total ischaemic time for over 13 000 registry patients. They found that a male patient is reperfused on average within three and a half hours of having a STEMI, while women typically experience an additional half hour of ischaemia.

But despite everything you’ve heard so far, in-hospital management only accounts for 7 and a half minutes of this gender gap. The researchers call this the “door-to-balloon” time while the time it takes to present is called the “symptom-to-door” time. On top of the two hours reported for men, it takes women an additional 20 minutes to get to the ED.

So how do we explain this gap in response time? In part, it comes down to the very limited community awareness about women’s heart disease. According to research published in the journal Circulation, many women didn’t realise they were having a heart attack because it didn’t match the Hollywood stereotype. And in a Canadian survey, fewer than a third of women could identity four common symptoms of myocardial infarction.

It’s not just recognition of acute events that’s a problem, but also prevention. Fewer than a quarter of the Canadian respondents named high blood pressure or cholesterol as a risk factor, and smoking was recognised by half of them only. In fact, traditional cardiovascular risk factors
confer significantly more risk in women than in men—by a factor of three in the case of diabetes. You can’t blame women for their lack of knowledge, but according to Sarah Zaman, public awareness campaigns only go so far. 

SARAH ZAMAN:               I mean there has certainly been a lot of work in trying to improve awareness of heart disease in women, so ‘Invisible Me’ was one of the campaigns targeting women. But unfortunately even though we saw an uptick in increased awareness and women recognising that heart disease was their major killer, that seems to have then declined. And if you survey women now they still believe the majority of them, that breast cancer is their biggest risk despite heart disease being the number one killer. So I think with awareness campaigns it’s something that has to be ongoing, or unfortunately a lot of women don’t recognise that they’re at risk, and then that sort of feeds into them not then advocating for themselves. We’ve obviously got heart checks that have come out now that are Medicare rebated with your general practitioner, but once again we’re seeing that it’s a lower rate of women who are taking up this heart check. So it's critical that both the patient and the provider are aware that heart disease is the number one issue for women – number one killer.

MIC CAVAZZINI:               Beyond those high-profile campaigns the public gets most of their health education from their GP probably, and women are less likely to be asked about cardiovascular risk factors by their GP. Researchers from the George Institute sampled GP records of over 53,000 patients and found that female patients were 22% less likely to have their smoking status recorded, 12% less likely to have their systolic blood pressure recorded, and 8% for cholesterol. Again, are these considered more ‘masculine’ problems?

SARAH ZAMAN:               Yeah, I think so. Even if there is a diagnosis of coronary disease there’s still this image that women are lower risk, and therefore they receive less preventative therapy – and not to mention all the lifestyle changes that we can do. And I think the other issue as well is that there’s also female specific or non-traditional risk factors that are even more poorly recognised. So you could have a woman who’s had a history of preeclampsia, gestational diabetes, premature menopause before the age of 40, and all these risk factors are little discusse—the patient won’t know about them, even the general practitioners might not be aware of them, and unfortunately they don’t then get targeted for blood pressure control, for screening for further diabetes, etcetera.

But there are other things that you can do if you’re looking at risk stratification in younger women. So we use either a Framingham Risk Score or we use the Australian absolute cardiovascular risk calculator, and if you’re a woman under the age of 65 you invariably come up as low risk, unless you have a whole stream of risk factors. But if you have one or two risk factors automatically based on your age and your gender fall into a low-risk category, and therefore you’re probably less likely to be prescribed some of these preventative medications.

But I’m also a big believer in something called a calcium score. So there’s something called a CT-coronary artery calcium score. And if you have a female who is scoring maybe in the intermediate range on this risk score and they have some of these non-traditional risk factors then you can actually do a CT calcium score which is very low radiation, low cost, and that can tell you if they have any premature or coronary disease. And it can also guide what sort of medications you should give them.

MIC CAVAZZINI:               And you talk about the “symptom-to-door time” – according to a qualitative study published in 2015 in the journal Circulation, women don’t take themselves to get checked if they’re potentially having symptoms of MI because they’re worried about being seen as hypochondriacs. Is this something you’ve seen and can you understand why this paranoia exists?

SARAH ZAMAN:               Well it happens to both male and female patients who will stay at home with chest pain for a day or two but mainly because they think it’s not heart disease. I have numerous younger women who have turned out to have heart attacks who have stayed at home for a day or two just thinking that it couldn’t possibly be a heart attack, or they don’t want to be a burden to the health care system. There may be other biases playing in their mind in terms of not wanting to be perceived as anxious. And that’s what we’re trying to overcome by all these awareness programs because you don’t want a half hour delay if someone’s having an acute heart attack.

MIC CAVAZZINI:               In the next episode I’m going to go into the gender stereotypes a bit more but there’s a couple of findings that are specifically relevant. So in your review you cite the Genesis Praxy study from Canada where the researchers looked at rates of recurrence of acute coronary syndrome after men and women had been admitted for a major event. The patients filled out a questionnaire that allowed them to be scored on gender traits. So it asked about social roles and household roles such as, “Are you the primary earner or child carer?” It asked about personality traits like confidence and dealing with stress, and also the level of “institutionalized gender” based on education and income. So the study found that just being biologically female didn’t predict higher recurrence of coronary events. But scoring as highly feminised did predict this – whatever sex you identified with. What do you make of that? 

SARAH ZAMAN:               Yeah, I mean I think it’s really important. A lot of our – this is why there’s a difference between sex and gender because gender is our societal restrictions whereas sex is just our biological sex. And look, I’m not surprised that gender traits were very predictive because it’s all about that perceived role in culture and society. And yeah sure, maybe some of these traits mean that you’re less likely to advocate for yourself, maybe you’re going to be less likely to prioritise the cost of your medications, taking your medications – your ability to prioritise exercise as opposed to looking after your child or your family or your household. So I mean it all makes sense. I can’t say I’m an expert in gender constructs though – but yes. But I mean apart from addressing all of society it’s hard as a cardiologist to fix that problem, I think.

MIC CAVAZZINI:               We’ll try and solve all of society’s gender constructs in the next episode. Please keep an eye out for that. For now, I want to thank Sarah Zaman for contributing so much to this episode of Pomegranate Health. The views expressed on this podcast may not represent those of the Royal Australasian College of Physicians. 

You can chase up any papers and lectures mentioned in this podcast at our website racp.edu.au/podcast. There’s a transcript with all the links embedded and Fellows of the College can log credits for participating in this educational activity at the MyCPD link provided.

At the website I’ve also thanked individually the Fellows who provided feedback for this story, and I’m truly indebted to the whole editorial group for finding the time to continue supporting the podcast over the last year. There is opportunity for new members to join the group for 2021 to provide input into future podcasts. If you’ve got an ear for podcasts and think you’d like to contribute follow the links at our website to the Expression of Interest forms. These are to be emailed by February 21st to the address podcast@racp.edu.au.

I hope to hear from you. I’m Mic Cavazzini.

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11 May 2021
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