Unravelling race inequities in cardiovascular disease mortality among cancer survivors: new insights and future directions

In their article, ‘Mediators of Black-White inequities in cardiovascular mortality among survivors of 18 cancers in the USA’, Sung and colleagues quantified the extent to which racial differences in cardiovascular disease (CVD) mortality among cancer survivors are mediated by socio-economic and clinical factors.¹ Given that cancer survivors are more likely to be diagnosed with CVD than the general population,² uncovering the factors that mediate the racial inequities in CVD-related mortality may facilitate the development of relevant interventions. Although previous studies have investigated the relationship between socio-economic status and CVD mortality among cancer survivors,^3,4 none has quantified the contribution of the mediators to excess CVD mortality among Black cancer survivors or assessed heterogeneity across multiple cancer sites.

By leveraging Surveillance, Epidemiology, and End Results (SEER) registry data among Black and White cancer survivors diagnosed between 2007 and 2016, the authors reported that Black survivors had a higher risk of CVD mortality than White survivors across all 18 adult-onset cancer types. The excess risk was lowest for lung (hazard ratio = 1.3) and ranged up to 4.0 for brain cancer. Socio-economic characteristics [e.g. health insurance, neighbourhood socio-economic status (nSES) and rurality] were shown to mediate racial disparities in CVD mortality, with nSES accounting for ∼15% to nearly 64% of the racial inequities in CVD mortality among cancer survivors. Health insurance was the second most important mediator of racial inequities in CVD mortality (percent mediated ranged from 12% to 31%). For most cancers, clinical characteristics (e.g. stage, tumour subtype and cancer-directed treatments) mediated disparities to a much lesser extent.

The authors suggest updating clinical guidelines to incorporate social determinants of health (SDoH) as one approach to narrow race disparities in CVD mortality among cancer survivors. However, there remain important knowledge gaps in our understanding of SDoH, baseline CVD risk and treatment-related effects on CVD mortality that would aid in the development of such guidelines and inform intervention.

Neighbourhood SES is a composite index that includes a range of factors related to the economic and social conditions of an area (e.g. poverty, education, employment, income and home value) and may further reflect unmeasured component causes. For example, home value reflects aspects such as neighbourhood investment, residential racial segregation and the social and political capital of an area. Thus, it is unclear which factors related to nSES drive racial disparities in CVD mortality, as they are intersecting, and disentangling their effect would require more advanced decomposition approaches. Neighbourhood SES likely serves as a proxy for factors with direct clinical relevance. For instance, it could reflect general access to healthcare resources (density of providers and transportation) or built environment (food availability and the presence of green space). Each would require distinct interventions and robust co-ordination of healthcare institutions and local and state governments. Thus, whereas composite measures such as nSES are necessary for political action and high-level interventions that broadly address SDoH, additional granularity in our assessments will aid in the development of specific approaches to addressing these gaps (e.g. expansion of public transportation, improving healthy food access or creating safe and attractive public spaces that promote physical activity), helping to mitigate—rather than simply document—disparities. Given the intractability of race and racism in the USA, it is important to have well-defined mediators when assessing drivers of health inequities. Further interrogation into the contribution of specific aspects of nSES, and their component causes, can offer concrete and actionable strategies to reduce CVD mortality disparities among Black cancer survivors.

Completely absent from the present study were the myriad of concurrent health conditions often present at the time of cancer diagnosis that impact cancer treatment, side effects and cardiovascular health throughout the survivorship period.^5,6 Previous studies have shown that the net burden of comorbidities, specifically obesity, are higher among Black cancer patients, which may underlie the observed disparities in CVD mortality.^7,8 Notably, there exists a strong positive association between nSES and cardiometabolic health, with prior studies reporting greater rates of obesity among individuals residing in low-SES neighbourhoods.⁹ Although the precise mechanisms through which neighbourhood factors influence cardiometabolic health are likely multifaceted, the environment (access to green space and healthy foods, presence of environmental toxicants), sleep and chronic stress (crime, noise pollution) play a pivotal role.¹⁰ Future work aimed at mitigating racial disparities in CVD mortality among cancer patients must incorporate information on comorbid conditions alongside neighbourhood factors. Such an approach will enhance clinical guidelines, provide clear targets for intervention and ultimately enhance the efficacy of efforts to reduce racial disparities in cardiovascular outcomes among cancer survivors.

Although the SEER database serves as a valuable repository for cancer incidence and mortality data, it lacks more granular information on cancer treatments—information essential for identifying targeted clinical interventions to mitigate the cardiotoxicity associated with multiple cancer therapies. For example, in the case of HER2+ breast cancer, the administration of trastuzumab is a standard component of guideline care. It has been shown to have increased cardiotoxic effects among Black breast cancer patients.^4,11 Similarly, among patients with oestrogen receptor-positive breast cancers, the prescribed 5–10 years of adjuvant endocrine therapy (aromatase inhibitors) has been linked to increased cholesterol levels and cardiac events in specific individuals.^12,13 Limited research has been conducted on race differences in cardiotoxicities. One study reported that Black patients treated with doxorubicin (an anthracycline chemotherapy) had a 3-fold increase in cardiotoxicity compared with non-Black patients.¹⁴ Failure to assess cardiometabolic conditions as part of cardio-oncological care may partially explain these disparities; however, with emerging targeted therapies (e.g. immunotherapies), additional research is needed to understand differences in cardiotoxicity on the backbone of baseline CVD risk.

In recent decades, advancements in cancer treatment have dramatically improved cancer-specific survival rates. As such, individuals with certain cancers face a considerable burden of morbidity and mortality from CVD—with Black survivors disproportionately afflicted. This study provides valuable insights into the clinical and socio-economic factors influencing CVD mortality. Yet, with the exception of lung cancer, ∼25–75% of the race effect was unexplained for most cancers and may reflect other mediators, including certain aspects of the neighbourhood environment, baseline CVD risk or treatment-related cardiotoxicity. Future work should continue to incorporate mediation approaches to identify tangible targets for intervention.

Data availability

There are no data to accompany this commentary.

Author contributions

L.E.M. conceived the commentary, outlined the initial draft and had oversight for the final product. L.J.C. and M.S. reviewed the literature and provided content for the final draft. All authors approve this commentary.

Funding

Lindsay J. Collin was supported by K99CA277580 from the National Cancer Institute of the National Institutes of Health.

Conflict of interest

None declared.

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