Patient perspectives on priorities for research on conventional and sex- and gender-related cardiovascular risk factors

On 15 November 2018, the panel received an email invitation with a hyperlink to an anonymous online survey (in Dutch) that was available for 7 weeks. Completion of the survey was voluntary. No personal reminder could be sent because the survey was anonymous and a general reminder would pose too great a burden on the panel at large. As the Dutch Medical Research Involving Human Subjects Act did not apply to this study, explicit ethical approval was not needed.

The survey included instructions and a brief introduction into the topic, followed by general questions on sociodemographic variables (age, country of birth, parents’ country of birth, sex, gender identity [personal perception of one’s own gender: man, woman, non-binary, gender fluid, transgender, transsexual, other], and educational level) and history of CVD. As a measure for priority setting, we asked respondents to choose a maximum of 3 out of 16 conventional risk factors (mentioned on the website of the Dutch Heart Foundation [11]; see Tab. 1 in Electronic Supplementary Material) on which they would like to spend a fictional research budget for new research within their gender group (‘Imagine that you can spend one million euros on more research on risk factors in your gender group. On which studies would you spend this money? You can choose a maximum of three’). Respondents could explain their choice in an open-text field (‘If you wish, you can elaborate on your choice of risk factor(s) below’).

As a measure of perceived relevance of new research on their chosen risk factors, we asked respondents to rate the importance of their budget allocation on a scale from 1 to 10 (’How important do you think it is to spend this money on new research on at least one of the three chosen risk factors? With ‘1’, you indicate that you think it is not important at all new research will be initiated, and with ‘10’, you indicate that you think it is very important new research will be initiated’).

We asked the same questions for 19 sex- and gender-related risk factors (Tab. 2 in Electronic Supplementary Material). These were characteristics, behaviours or conditions that were not considered conventional, such as hypertension and stress [11], and that were chosen based on previous research [3, 12‐20].

Finally, to identify any other factors that might be related to CVD risk according to the respondents, they could suggest additional factors in an open-text field. All questions were closed-ended, except the 3 open-text field questions.

We analysed sociodemographic data and history of CVD descriptively, depicting them as percentage and mean ± standard deviation (SD). Gender group was based on the individual’s sex at birth combined with self-reported gender identity, and classified into cisgender men (those identifying as men or who were assigned the male sex at birth), cisgender women (those identifying as women or who were assigned the female sex at birth) and other gender groups. Ethnicity was defined using the validated country of birth indicator, by combining the individual’s country of birth with the parental countries of birth. We distinguished between a Dutch, non-Western migration and Western migration background [21, 22]. Educational level was classified into high level (higher vocational schooling or university) and other.

All data on conventional and sex- and gender-related risk factors were descriptively analysed as mean ± SD, stratified by gender group. All analyses were performed in IBM SPSS Statistics 25. The open-text field questions were summarised, but not further analysed.

After the first survey, we distributed a shortened version of it to a convenience sample of 52 women with a non-Western migration background, who were recruited at local markets in Amsterdam, the Netherlands. We studied this group of women specifically because previous research has shown that they are a potentially overlooked high-risk group for CVD [23, 24]. Using this post hoc sample, we were also able to include a larger and more heterogeneous group of respondents with a non-Western migration background.

Of the 16 conventional risk factors, heritability was the most frequently prioritised by men (35%), closely followed by overweight and a generally unhealthy diet (Fig. 1a). More than half of the women chose stress as a priority for further research, followed by heritability and hypertension. Around 26% of men and 30% of women elaborated on their choices (Tab. 3 in Electronic Supplementary Material). For instance, the high priority for heritability (frequently labelled as ‘genetics’) was often linked to a high CVD frequency in the family, without explicit consideration of the possibility of shared (unhealthy) lifestyles within the family.

Of the 19 listed sex- and gender-related risk factors, more than half of the men chose depression or depressive feelings as a priority for further research, followed by migraine and having many caretaking responsibilities (Fig. 1b). Women most frequently prioritised pregnancy complications (33%), closely followed by contraceptive pill use and early age at menopause. Around 13% of men and 17% of women elaborated on their choices, with similar reasons as those for the conventional risk factors (Tab. 3 in Electronic Supplementary Material). For instance, some respondents reported that their pregnancy complication or migraine may have been the cause of their CVD.

Among men, the mean score with regards to budget allocation for their 3 chosen sex- and gender-related risk factors was 7.4 ± 1.5, slightly lower than that for conventional risk factors (8.3 ± 1.2). Among women, the importance of sex- and gender-related risk factors was rated more similar to that of conventional risk factors (8.6 ± 1.2 vs 8.2 ± 1.4).

In the open-text field, around 18% of men and 25% of women mentioned additional risk factors, such as variations on previously mentioned risk factors (e.g. late age at menopause), comorbidities and associated treatments (e.g. cancer and chemotherapy), (chronic) medication use and environmental factors (e.g. particulate matter).

Among non-cisgender respondents (n = 9) and respondents with a non-Western migration background (n = 11), we observed slightly different response patterns. For instance, heritability was not a priority according to men and women with a non-Western migration background, whereas stress was additionally prioritised by men with a non-Western migration background. Furthermore, depression or depressive symptoms (by women with a non-Western migration background) and gender discrimination (by non-cisgender respondents) were additionally identified as priorities (data not shown).

Results based on our post hoc sample of 52 women with a non-Western migration background were consistent with those based on the minority respondents of the panel. Hypertension, diabetes and stress (rather than heritability) were reported as priorities for further research. Moreover, the women in the post hoc sample more often deemed both sex-related (e.g. pregnancy complications) and gender-related risk factors (e.g. gender discrimination) priorities for new research than the majority panel did (data not shown).

Our study has some limitations. First, we targeted CVD patients specifically as we were interested in patient perspectives on prioritisation of risk factors for additional research. As a result, our findings may be less generalisable to the general Dutch population, which is younger and at lower CVD risk than our study population.

Second, the convenience sample of women with a non-Western migration background was recruited via an alternative route and most of these women did not have CVD. However, this group reported similar priorities as the ethnic minority subgroup included in the panel, suggesting that the lack of a CVD history does not explain the differences between the majority and minority groups.

Third, although our findings provide relevant information on priority setting for research in patients with CVD or in individuals at increased CVD risk, our study offers only limited insight into the reasons and motivations behind this priority setting. For instance, differences in reasons for prioritisation of risk factors between men and women could not be established due to a low response to questions requesting elaboration of choices. Nevertheless, our findings suggest that choices were frequently based on personal experiences. These experiences, for instance with sex- and gender-related risk factors in clinical practice, could be further investigated.

Ethnic minority populations might be at a higher risk of CVD than majority populations [25, 26]. Accordingly, European guidelines have emphasised the need for more research on CVD risk in these groups [27]. We found that minority respondents prioritised risk factors related to sociocultural aspects (e.g. gender discrimination) frequently, more so than the majority panel. This may reflect a higher exposure to sex- and gender-related risk factors or an increased vulnerability to their impact among men and women from minority groups [28, 29].