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Page 10 of 17 Ghunaim et al. Vessel Plus 2023;7:29 https://dx.doi.org/10.20517/2574-1209.2023.112

In terms of biological predisposition, particularly at an older age, there is evidence that women lose the
[116]
cardioprotective benefits of estrogen following menopause . Additionally, early menopause, pregnancy-
associated conditions, such as gestational hypertension, gestational diabetes, preeclampsia and eclampsia,
and maternal autoimmune disease, all increase the risk of premature CAD in women [117,118] . In addition,
studies suggest differential pathophysiology of CAD in White vs. Black patients . CAD in Black patients
[78]
may be manifested by small-vessel disease resulting in chronically increased oxygen demand, while it is
related to greater epicardial vessel atherosclerosis and acutely decreased oxygen supply in White patients .
[78]
With regards to revascularization, Asian patients may have coronary arteries that are smaller in diameter
than those in White patients, leading to more challenging CABG procedures . Moreover, Asian
[119]
individuals have a unique antiplatelet feature, also known as the “East Asian paradox”, with patients
suffering from higher bleeding rates and lower ischemic events after undergoing PCI . However, further
[120]
research is needed to elucidate whether these physiological differences are predominantly mediated by
environmental, social, or genetic factors.

From a “nurture” perspective, many social factors may compound to impact patients’ access to care and
outcomes. Health literacy, particularly as it pertains to cardiovascular disease, tends to be lower among
women, lower socioeconomic, and racial and/or ethnic minority patients [121,122] . The prolonged ischemic
duration among women with ACS has been historically associated with decreased symptom recognition by
patients and providers [121,123] . From the care delivery perspective, young women with CAD are less likely to
[125]
be asked about their cardiovascular risk factors or receive counseling on risk modification .
[124]
Additionally, patients from racially and/or ethnically minoritized groups may experience systemic racism
that predisposes them to worse outcomes. Following an acute myocardial infarction, Black patients
experience greater case fatality rates than White patients living in low- and medium-income areas,
suggesting compiling social factors that underlie social disparities in outcomes . Despite having a greater
[126]
comorbidity burden, racially and/or ethnically minoritized groups are more likely to have lower
socioeconomic means, leading them to present to low-volume and/or low-quality facilities in the United
States [77,107,108,112] . Racial and/or ethnic disparities in revascularization may be explained by racial segregation,
referral patterns, and geographic proximity to cardiac centers [107,127] . Therefore, multilevel systemic
interventions targeting healthcare providers and vulnerable communities are needed to promote health
literacy, identify high-risk patients, and provide them with comprehensive cardiovascular care.

KNOWLEDGE GAPS AND WAYS FORWARD
Despite the poorer outcomes observed among women and racialized and/or minoritized patients, they have
been historically underrepresented in cardiovascular trials, further exacerbating the gaps in care [128,129] . This
may be the result of mistrust in healthcare, historical discrimination, insufficient diversity of research
leadership, and related social factors such as socioeconomic status, geographical location, education, and
health literacy [107,128,130] . Promoting diverse representation in clinical trial leadership and trial participants is
the first step in identifying and addressing gaps in cardiovascular care delivery. There is a need to address
the barriers and causes of underrepresentation and variable enrollment of different populations in
[129]
cardiovascular trials . Moreover, further investigation is warranted to determine to what extent the
observed differences in outcomes are the result of genetic factors, risk factors, sociodemographic factors,
and systemic factors. For instance, the regionality of atherosclerosis may differ across different ethnicities,
which can contribute to observed differences in outcomes . Lastly, intersectionality in disease burdens ,
[130]
[126]
access to care, and outcomes after care must be recognized to reflect patients’ unique intersecting identities,
whereas differential patient preferences and needs must be respected. In response, the National Institute of
Health Revitalization Act of 1993 established “policy and guidelines for the inclusion of women and
minorities as subjects in clinical research”, with its 2017 update adding the requirement for Phase III clinical