Sex and Gender Issues in Cardiovascular Disease: Introduction to a Special Issue

Cardiovascular disease (CVD) is the leading cause of death for both women and men worldwide.1 Over the past several decades, there have been significant improvements in survival and quality of life, due in part to advances in CVD treatment. Despite these advances, young and midlife women have less favorable incidence and mortality trends compared with men and older women.2 Ongoing gaps in knowledge about female-specific CVD pathophysiology, including biological and sociocultural contributors,3 paired with the fact that current guideline-directed therapies are based on data derived from studies predominantly of male participants,4 serve to undermine women’s CVD prevention and clinical care. In addition to biological sex, emerging data indicate that gender profoundly influences exposure to stress5 and cardiovascular health and outcomes.6 Finally, there is mounting evidence that sexual orientation and gender identity are associated with disparities across several CVD risk factors, likely driven by exposure to psychosocial stressors across the lifespan.7 Despite this growing body of evidence and advances in research and treatment, the distinct and intersectional contributions of biological sex, gender and related sociocultural factors, and disparities related to these identities to the manifestations and outcomes of CVD, remain poorly understood. Women and gender-diverse populations remain underrepresented in cardiovascular trials, leading to incomplete knowledge about optimal prevention and treatment strategies. The current special issue of Biopsychosocial Science and Medicine brings together 12 compelling contributions that deepen our understanding of how sex, gender, and psychosocial factors intersect to shape cardiovascular health and disease. Collectively, these papers reflect the growing recognition that cardiovascular outcomes cannot be fully understood through biological mechanisms alone but must also be viewed through the lenses of social context, identity, and lived experience. The studies span a broad methodological spectrum—from experimental animal models to longitudinal clinical cohorts—and examine topics ranging from sex differences in coronary artery disease and cardiac remodeling to the psychological and social determinants of cardiometabolic risk. Several studies focused on sex differences in how established psychological risk factors affect CVD risk, with most of them, but not all, highlighting increased risk for women. In a study by Sanchez-Carro et al,8 lower subjective social status may be particularly important to women’s cardiac health (as assessed by a subclinical marker of cardiac fibrosis) relative to men. In contrast, work from Wang et al9 has indicated that among patients with acute coronary syndrome, type D (distressed) personality traits are associated with poorer underlying vascular health among men relative to women. In addition, Kim et al10 showed that male caregivers showed blunted RMSSD, heart rate, and diastolic blood pressure reactivity to a stress induction task, while female cancer patients displayed a greater cardiovascular reactivity. Finally, in a study of adult rats from Barbetti et al,11 sex differences in epigenetic processes were found underlying dissimilarities in the cardiac response to social stress, with increased vulnerability in male rats. Several papers in this issue highlighted the effects of emotion regulation, trauma exposure, and chronic stress on women’s cardiovascular health. In a study of postpartum women by Kofman et al,12 being exposed to perinatal traumatic experiences was prospectively associated with an increased risk of depressed mood, as well as adverse CVD risk marker. Work by Spikes et al13 underscored the importance of physical and emotional abuse for vascular function in women. Other studies in this issue highlight that emotion regulation approaches, either behavioral or pharmacologic, have implications for cardiovascular health. Leveraging the Nurses’ Health Study II cohort, Trudel-Fitzgerald et al14 showed that higher use of reappraisal was prospectively linked to better cardiovascular health 2 years later in women who used this strategy. In a case-control study of women with incident Takotsubo syndrome and control women with a recent myocardial infarction, Ouaddi et al15 showed that the use of catecholamine or serotonin reuptake inhibitors prediagnosis was more prevalent in Takotsubo cases than in controls, after taking into account their psychiatric history. Future mechanistic studies are needed to disentangle how neurobiological processes associated with mood, trauma, and emotion regulation may affect cardiovascular health. Other papers explored how gender norms, sexual minority identity, and race-related stress contribute to disparities in cardiovascular indicators. Hascher et al. found that stressors related to being lesbian, gay, and bisexual, including disclosure and concealing of sexual minority health, were not statistically significantly related to cardiovascular health in the CARDIA cohort, although conclusions should be tempered by the small sample size.16 Two papers on Black women, both applying latent class analysis to more precisely define within-person risk characteristics, found a link between the psychological sphere and cardiovascular health. Work by Volpe and Collins17 examined latent within-person profiles of cardiovascular health, showing that young Black adult women in the moderate/high cardiovascular health class had fewer symptoms of emotional distress compared with classes characterized by less optimal cardiovascular health. Hoggart et al18 underscored the importance of police-related stress to cardiovascular health in women, finding that women (mothers) with high vigilance regarding their children encountering police had elevated carotid atherosclerosis. Finally, van den Houdt et al19 prospectively examined sex and sociocultural gender norms as predictors of 5-year medical outcomes and mortality in patients with coronary heart disease, showing that more feminine sociocultural norms, rather than sex itself, was associated with an increased risk of CVD events and mortality. Together, these contributions illustrate the critical importance of integrating sex and gender considerations into cardiovascular research and clinical practice. They urge the field to move beyond a sole focus on sex or gender but consider their dynamic interplay when understanding the contributors to and management of heart health across populations. BROADER IMPLICATIONS AND FUTURE RESEARCH AGENDA Across a broad array of topics, study designs, and populations, the papers published in this issue point towards the importance of sex and gender-specific characteristics of cardiovascular risk. They underscore the importance of considering not only sex differences in CVD but also how gender can impact CVD risk and recovery. As such, they point to the importance of gender as a key social determinant of health, patterning both ones lived experience and associated health outcomes. Beyond sex and gender, achieving equitable cardiovascular health requires an intersectional lens, inclusive research practices, and culturally informed research methods. Cardiovascular risk profiles and disease trajectories vary not only by sex and gender but also by race and ethnicity, yet many populations remain significantly underrepresented in cardiovascular research. There is increasing awareness of the importance of moving beyond passive recruitment approaches to actively engaging with communities through partnerships built on trust, mutually supportive relationships, cultural competence, and respect for participants’ lived experiences. Moreover, advancing our research requires consideration of intersecting identities—such as by race, ethnicity, gender, and disability status among others—and their implications for CVD risk. The papers in this issue also highlight challenges of research. When considering participant’s diverse and intersectional identities, larger sample sizes may be required to study subgroups with sufficient statistical power. This research may also present specific methodological and statistical challenges pertaining to intersectionality that require ongoing consideration. In addition, more longitudinal research is needed to examine how associations between sex, gender, and CVD risk develop over time. Psychometrically, there is a need for more in-depth development of the conceptualization and measurement of gender that can be used across studies of sex and gender. This work has clinical and public health implications. Systematically identifying how cardiovascular and psychosocial factors differ by sex and gender and how they influence CVD—from molecular mechanisms in animal models to clinical manifestations in patients—improves the potential to develop more accurate risk assessment tools, tailored disease prevention strategies, and therapeutic interventions that maximize efficacy across sexes and genders. These approaches would consider not only biological sex-related determinants but also gender and related psychosocial experiences. Such a sex and gender-informed approach holds potential to reduce sex and gender health disparities and improve early detection and treatment of CVD across populations. We hope the collection of papers in this special issue provides further impetus for studying sex and gender related differences in cardiovascular risk in health and disease.