Disparities in Cardio-Oncology

In the United States, cancer and cardiovascular disease (CVD) are the two leading causes of death ⁴ and share many risk factors such as age, gender, obesity, and diabetes ⁵. Notably, it has been shown that cancer patients experience a greater likelihood of dying from CVD than the general population ⁶, and that receiving a new cancer diagnosis is associated with an increased risk of dying from CVD compared to individuals without cancer ⁷. Despite improvements in early detection and treatment, there are similar disparities in cardiotoxicity outcomes among ethnically diverse populations, minoritized and marginalized groups, and women ^{8, 9}.

In the American Heart Association scientific statement titled "Equity in Cardio-Oncology Care and Research," Addison et al. seek to understand the factors contributing to disparities in cardio-oncology. Within the statement, the impact of cardiotoxicity on various populations is examined, primarily focusing on sex and population-specific differences, highlighting the importance of diversity in clinical trials, and providing strategies for reducing inequity in cardio-oncology. This statement is an essential step toward achieving health equity in cardio-oncology care.

How Does Inequity Impact Cardio-Oncology?

A clear definition of health equity is vital to achieving it as it requires a collaborative effort among many stakeholders and an understanding of its multilevel etiology ¹⁰. Health equity refers to a fair and just opportunity for all individuals to achieve good health by removing barriers to health, such as poverty and discrimination. Conversely, health disparities are systematic and potentially preventable differences that adversely affect economically or socially disadvantaged groups ¹⁰. Therefore, health inequities are considered unfair practices and reflect unjust systems that result in health disparities ¹⁰. The statement authors discuss various cardio-oncology inequities across multiple groups, including female, Black, Hispanic, Asian and Pacific Islander, LGBTQIA+, and pediatric populations. These inequities can arise for several reasons, including social determinants of health, racism, and lack of diversity in clinical trials, as discussed in this scientific statement. The statement authors demonstrate how addressing these inequities is essential to ensure equitable care in cardio-oncology.

How Does Cardiotoxicity Affect Marginalized and Pediatric Populations?

Within this scientific statement several studies are presented demonstrating sex differences in cardiotoxicity risk, with women bearing the greater risk. A meta-analysis of 23,296 patients in 202 phase II and III clinical trials from 1989 to 2019 examined sex differences in adverse events across treatment domains, including chemotherapy, immunotherapy, and targeted therapy, and found that women had a 34% higher risk of severe adverse events across all treatment domains compared to men ¹¹. CVD is the leading cause of death for women in the United States, and in the absence of protection from sex hormones, it is not surprising that postmenopausal women receiving treatment for their cancer may also be at increased risk for cardiotoxicity ¹². In addition, anti-estrogen therapy has been linked to an increased risk of CVD and stroke in some breast cancer patients and postmenopausal women ¹². The same study found that in women treated with traditional chemotherapies such as anthracyclines, variations in cardiac risk factors have been identified as contributing factors to their cardiotoxic risk ¹². These studies examined by the authors highlight the importance of considering sex differences to better understand and effectively manage the cardiotoxicity risk in women.

Cultural and societal factors may influence the disease prevalence and treatment differences experienced by ethnically diverse patients. Black patients have an increased risk of CVD and also suffer an increased risk of cardiotoxicity, as demonstrated in breast cancer populations ¹³. CVD and mortality risk is greater for this population, even when controlling for socioeconomic, cancer stage, and treatment-related factors ^{9, 14, 15}. Further, emerging data show that androgen deprivation therapy, used for early prostate cancer treatment, may also increase the risk of cardiovascular adverse events ¹⁶. Disparities in incidence and mortality in CVD and prostate cancer warrant additional studies on the impact of androgen deprivation therapy on cardiotoxicity in Black prostate cancer patients. Disproportionately higher rates of hypertension may also increase the risk of cancer therapy-related cardiac disease in Black populations ^{15, 17}. Cultural practices surrounding diet and socioeconomic factors may affect health habits, contributing to hypertension and CVD. Furthermore, cardiac monitoring varies according to race and ethnicity among cancer survivors receiving anthracycline therapy. Specifically, Black patients have significantly fewer baseline echocardiogram assessments and more cardiovascular risk factors, such as diabetes, obesity, and hypertension, than non-Hispanic White patients ¹⁸. These factors also increase the risk of heart failure in patients receiving anthracycline therapy. Therefore, it is vital to identify and assess heart failure risk factors before starting anthracycline therapy in Black patients ¹⁸.

Hispanic patients also receive significantly less cardiac surveillance than non-Hispanic White patients ¹⁸. For this reason, clinicians must understand social inequities and implement cardiac evaluation and active surveillance recommendations to improve health outcomes of patients receiving anthracycline therapy, especially racial and ethnic minority patients ¹⁸. In Hispanic/Latin populations, cancer diagnoses are similarly made at later stages compared to non-Hispanic Whites, necessitating more cardiotoxic treatment regimens and precipitating a higher incidence of cardiotoxic treatment-related complications. Like in the Black population, cancer and CVD are leading causes of mortality in Hispanic as well as Asian and Pacific Islander populations. Further, many of these populations are more heterogeneous than data collection illustrates, with unique national origins and cultures, which may influence cancer and cardiovascular risk ^19-21. Additionally, this scientific statement contains discussion about the collection of vulnerability data, such as language barriers, mistrust of health care providers, systemic racism, discrimination, and societal and psychosocial influences. These are necessary to further explore inequities and how factors beyond documented differences in treatment intensity affect outcomes.

Individuals who identify with a sexual orientation other than heterosexual or a gender other than their sex assigned at birth also experience healthcare inequities and structural discrimination. This effect is compounded for individuals who hold multiple intersecting marginalized identities. Further, LGBTQIA+ populations have been identified as at increased risk for CVD and cancer, and subsets of this larger group are more likely to report conditions that can increase cancer and CVD risk, such as tobacco use, obesity, and HIV, than those who identify as cisgender and heterosexual ²². To combat these inequities, sexual and gender demographic data should be gathered in cardio-oncology patients, in addition to efforts to reduce gendered language and increase visibility and representation.

Long-term morbidity and mortality in pediatric cancer survivors have increased as survival rates of childhood cancers have improved ²³. As the population of childhood cancer survivors has grown, so has the body of research describing the cardiotoxic effects of childhood cancer treatments and the importance of prediction, screening, and early mitigation of CVD risk factors to improve cardiovascular outcomes ²⁴.

What are Non-Biologic Drivers of Disparities in Cardio-Oncology?

Social determinants of health, including poverty, neighborhood disadvantage, racial discrimination, lack of social support, and geographic location, impact health disparities faced by minoritized groups through reduced access to healthcare services, nutritious food, and education and employment opportunities ^{21, 25, 26}. Environmental and psychosocial stressors have been identified as contributing to disparate health outcomes through limitations in social, economic, and financial advancement. However, processes have been identified to restructure workplace, neighborhood, and school systems in favor of those which optimize health impacts ^27-29. The authors suggest strategies and interventions should be implemented to reduce disparities in health care, such as improving clinician-patient identity congruence and cultural competence and humility. For example, it has been demonstrated among minoritized patients that some patients experience more favorable outcomes and adherence to visits and care when receiving care from providers of their corresponding gender and race ^{30, 31}. Another area in which representation benefits clinical outcomes is clinical trial diversity, in which equitable distribution of patients within trial registries is needed to translate research into best practices for all patient populations.

How can we Promote Health Equity in Cardio-Oncology?

The statement authors provide several strategies to improve equity in cardio-oncology. One of the main strategies discussed is the intentional diversification of clinical trials. A lack of diversity in clinical trials is a persistent issue in healthcare overall, which can worsen health disparities. An examination of cardiovascular clinical trials on ClinicalTrials.gov from 2000 to 2019 funded by the National Institutes of Health found that in 46% of trials, fewer than 25% of enrolled participants were Black ³². Moreover, out of the 62 clinical trials examined, 13 explicitly stated recruitment objectives for historically underrepresented groups, and only one of the trials reported meeting their target goal for recruiting Black participants ³². The authors suggest several interventions to address the lack of clinical trial diversity, such as expanding clinical trial eligibility, using standardized screening processes for study participants, and the Diversity Site Assessment Tool ³³. The statement contains recommendations that clinical trial sites regularly assess clinical trial diversity and define recruitment targets, as this is associated with higher enrollment rates for Black participants ³². Promoting cultural humility and reducing bias among clinical trial staff are also advised to improve greater patient engagement and increase enrollment.

The authors also suggest incorporating social determinants of health into clinical care delivery and increasing awareness of social and financial inequities. The authors propose telehealth utilization as virtual visits may enable more equitable access to medical care by reducing disparities caused by geographical, financial, and mobility-impairment barriers ³⁴. Other strategies recommended by the authors include providing non-English speakers with reliable interpretation services, using electronic health records to supplement clinical trial data, and creating a more diverse physician workplace. Finally, another strategy identified by the authors to improve equity is investigating biological pathways and factors that affect cardiotoxic risk and disease severity to provide personalized care.

Conclusion

Health equity plays a vital role in cardio-oncology because cancer and CVD disproportionately affect specific populations, including women, racial and ethnic minorities, the LGBTQIA+ community, and those with low socioeconomic status. Failing to address cultural, societal, clinical, and research disparities leads to worse outcomes for these racially and ethnically diverse, minoritized, and marginalized groups. For this reason, it is imperative to identify and address the drivers of disparities and work toward equity in cardio-oncology.