Wonder women: wondering where the women in cardiovascular trials are?

Women’s health is far more than ‘bikini medicine’.¹ Not only does cardiovascular disease (CVD) remain the leading cause of death for women, but CVD burden persists affecting over 275.2 million women worldwide, even after sex-specific targeted health campaigns.² Despite this burden, women, who comprise 49.6% of the global population, are consistently underrepresented in cardiovascular trials regularly making up about a third of cardiovascular trial populations.^2,3 Furthermore, this sex bias has remained largely unchanged over several decades.³ So why are women less likely to participate in cardiovascular trials? Does it matter, and if it does matter, what can be done to redress the balance?

Historically, women (specifically those of child-bearing potential) were excluded from trials and despite regulatory changes over the last 40 years, the pace of growth for the inclusion of women in trials has been slow. Although the current reasons for this are largely under-investigated, it has been reported that men have a 15% greater willingness to participate than women as women perceive greater risks and have distrust in trial participation.⁴ Similarly, sociocultural factors, for example childcare and other caring responsibilities, as well as logistical barriers such as inflexibility of working hours and transport costs⁵ also contribute to women’s ability and willingness to participate. However, the barriers extend beyond the women’s desire or ability to participate. Women do not have the same opportunities as their male counterparts to participate in cardiovascular research. Trial design, research culture ‘norms’, and researcher biases also considerably contribute to this challenge. Interviews with principal investigators have elicited that the concept of the ‘male norm’ persists in research culture and that the female body is more complicated to study so women are therefore more logistically difficult to include due to the increased time and funding that would be needed.⁶ As a consequence, researchers believe that male participants are more convenient to recruit when considering tight time and financial restraints.⁶

So, does it matter if women are under-represented in cardiovascular studies? As summarized in The Lancet women and cardiovascular disease Commission paper published earlier this year, sex disparities in outcome have been reported consistently in trials covering the breadth of cardiovascular conditions.² Similarly, sex differences of recognized (for example hypertension and diabetes) and under-recognized (for example psychosocial and environmental) risk factors exist and women also experience sex-specific cardiovascular risks (for example hormonal contraceptives and menopause), which are rarely recorded or included in risk prediction models.⁷ Women are also consistently under-represented in drug trials and in the US Food and Drug Administration previously withdrew a number of drugs (including cardiovascular) due to the increased adverse side effects experienced by women. Thus, as women with CVD are understudied, they continue to be ‘under-recognized, under-diagnosed, and undertreated’² as a consequence.

This situation clearly needs addressing. As with the problems, the solutions to improve women’s representation in cardiovascular trials must be multifaceted. Above all, women should be given equal opportunities to participate in cardiovascular research and researchers must prioritize the importance of the inclusion of women. As already highlighted in the literature, women must be made aware of available research opportunities⁸ and the benefits of participation² and then supported to alleviate the perceived or real barriers to participation including flexible hours and locations and accommodating childcare or transportation needs and costs.² Equally, trial-specific strategies should consider adjustment of exclusion criteria avoiding age limits,² stratified sampling to ensure a proper and fair representation of women, enrolling a sufficient number of women for sex-specific analysis^2,8 and sex-specific trial educational materials may also enhance recruitment.⁸ However, there is also a real need and opportunity for healthcare policy and funding organizations to take the lead in creating opportunities to enhance women’s engagement. Given more women are recruited to trials funded by national institutes for health,⁸ there is a responsibility for national institutes for health to set policy, standards, and financial support to give greater priority for research to explore potential biological pathways and under-recognized risk factors in women that may determine, or contribute to, sex inequalities in cardiovascular health.² One such example is that of the Canadian Institute for Health Research that is a signatory on two national policies relating to integrating sex and gender into health research (Government of Canada’s Health Portfolio Sex- and Gender-based analysis Policy and the Tri-Council Policy Statement on Ethical Conduct for Research Involving Humans) and expects all research applicants to integrate sex and gender into their research protocols when appropriate (https://cihr-irsc.gc.ca/e/50833.html). If research grant success were dependent on addressing research priorities for women, ensuring appropriate study design and representation of women, there would be greater incentive for researchers to tackle these challenges.

We should wonder no more. Women are under-represented in cardiovascular trials for a myriad of reasons that collectively result in poorer diagnosis, treatment, and outcomes. Such health inequality for a group of people making up almost half the population is unacceptable. We all have our part to play in creating and providing research opportunities, ensuring logistical barriers are eliminated, encouraging and supporting women to participate, achieving representativeness, reporting sex-specific outcomes from all trials, and then implementing the findings in practice.

The opinions expressed in this article are not necessarily those of the Editors of the European Journal of Cardiovascular Nursing or of the European Society of Cardiology.

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