Michael Lawless, Sarah Brown, Vijay Kunadian European Heart Journal, ehad452, https://doi.org/10.1093/eurheartj/ehad452
Each year, cardiovascular disease maintains its status as the leading cause of morbidity and mortality in women. In their most recent published statistics, the World Health Organization showed that ischaemic heart disease, stroke, and hypertension resulted in over 7.5 million deaths in women globally in 2019. This trend is similar to the mortality burden in men and is echoed by countries worldwide. Despite this, there remains a significant male predominance in practically all clinical trials measuring the safety and efficacy of investigations and management of cardiovascular disease, which ultimately directs clinical guidelines.
Coronary artery disease represents over 50% of the cardiovascular deaths of women, and over a third of all women in their fourth decade will go on to develop some degree of coronary artery disease. Women presenting with acute coronary syndromes (ACS), both ST and non–ST elevation myocardial infarction, suffer greater in-hospital mortality than men. Women are more likely to experience longer delays when it comes to presentation, investigation, diagnosis, treatment, and follow-up of coronary artery disease syndromes. Furthermore, women are less likely to receive the same guideline-directed therapy as their male counterparts who present with the same condition.
Why is there such a discrepancy between men and women in cardiovascular disease? Does this not represent a fundamental gender inequality and therefore implications for the human rights of women everywhere? The problem is, with to whom does the buck stop? Is it the public, clinicians, and policy-makers? Either way, we are all failing women everywhere. Two-thirds of all clinical research has been carried out in men. A review in 2018 of a broad spectrum of clinical trials for cardiovascular disease including heart failure, coronary artery disease, and ACS showed that women were under-represented in almost all. Furthermore, when they are included, women are more likely to be lost to follow-up during the trial period.
However, this problem goes far beyond the limitation of inclusion of women in clinical trials. A recent survey by the British Heart Foundation showed that there exist very real public misconceptions that cardiovascular disease, in particular stroke and ischaemic heart disease, is a problem mostly affecting men. The most universal symptom of ACS is chest pain, equally prevalent in women and men. It is curious then why studies have shown that women with symptoms of acute myocardial ischaemia typically present for medical assessment later than men. Could this phenomenon be explained by these public misconceptions? It is well established that delays in treatment of ACS increase mortality. A public mindset that our fathers and sons are exclusively ailed by ‘heart attacks’ is putting the lives of our mothers and daughters at critical risk.
Cardiovascular disease is associated with a multitude of risk factors, including smoking, hypertension, hypercholesterolaemia, and obesity. These remain important targets for intervention by public health and primary care physicians. These risk factors influence women differently to men. Women metabolize cholesterol differently to men, which contributes to a greater rate of development and progression of atherosclerotic cardiovascular disease. Women are less likely to uptake or maintain statin therapy. Smoking contributes an extra 25% risk of cardiovascular disease in women. Consumption of less fruit, vegetables, dairy, and fresh meat is associated with poorer cardiovascular outcomes in women. Furthermore, women are burdened by additional risk factors to men. Hormonal influences, menopause, age of menarche, pregnancy, and pregnancy-related diseases such as gestational hypertension and diabetes all play a role in the additional cardiovascular risk to a woman. Hormonal influence and cardiovascular risk are even more important to those who are transgender.
Women who suffer ACS are less likely to undergo percutaneous coronary intervention within the guideline-directed therapeutic window. This may be contributed to by the increased prevalence of non-obstructive coronary arteries in women, termed myocardial infarction with non obstructive coronary arteries or ischaemia with non obstructive coronary arteries. Alternative pathophysiology of the presenting ACS may blur the lines for clinicians to proceed with guideline-directed therapy; however, regardless of the underlying cause, women are less likely to be prescribed dual anti-platelet therapy, statins, and other secondary-prevention medications post-myocardial infarction than men. Fewer women are offered cardiac rehabilitation (CR) programmes following an acute coronary event. Women are also less likely to attend a CR session, particularly if they are from a black and minority ethnic background. Unfortunately, for those women who do attend a CR programme, the evidence suggests they do not gain the same level of benefit as men.
In 2023, it is hard to believe that women still face significant gender inequality and inequity. Greater emphasis is needed to eradicate the stigma that cardiovascular disease is a man’s domain. This may be achieved through greater promotion of health awareness by policy-makers, cardiovascular health charities, physicians, educators, and media; the list is endless. Outreach needs to focus on positive reinforcement that cardiovascular disease affects all and is actually worse for women and must aim to reduce the degree of ‘fake news’, which may ill-advise the public. Clinicians may facilitate this by encouraging women to attend their health checks (<50% of all patients currently attend these), encouraging health ownership by women in a similar vein that they may attend breast cancer and cervical screening appointments; and ensuring lifestyle modification and primary prevention is provided to those who are at greatest risk of cardiovascular disease.
Investigators who organize clinical trials must ensure greater gender equality in their recruitment. Reviewers of trial protocols should aim to highlight discrepancies in gender recruitment. More women-centric trials should be considered to focus on the investigation and management of cardiovascular disease in a vulnerable group who have greater and extra risk than men (see Figure 1).
Studies have focussed on in-hospital ACS care variability, which has sought to find a solution to the overall greater morbidity and mortality suffered by women. A 2018 cohort study of 1272 patients presenting with ST elevation myocardial infarction (STEMI) showed that sex disparities of in-hospital adverse events including death were reversed following the implementation of a simple, standardized four-step STEMI protocol facilitating direct access to the cath lab for all upon presentation. This study suggests that something as simple as an unbiased systematic approach to facilitate universal patient care is an effective strategy to reduce the gender inequalities faced by women with cardiovascular disease. Another study showed that in older adults with invasive treatment of non ST elevation acute coronary syndrome, provision of guideline-indicated care and long-term clinical outcomes were similar between males and females. Such strategies should be adopted in more hospitals throughout the world.
Women are subject to gender inequality and inequity when it comes to their cardiovascular health. There are numerous reasons why this may be the case; however, in 2023, this problem should not exist. We have explored some practical solutions to some of these common problems in order to raise awareness of the effects of cardiovascular disease in women and hope that these health discrepancies are resolved with urgency.
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Authors: Michael Lawless, Sarah Brown, Vijay Kunadian
Publication: European Heart Journal
Publisher: Oxford University Press
Date published: August 2nd, 2023
Copyright © 2023, Oxford University Press
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