Introduction

Cancer mortality rates have been consistently down-trending since the 1990s, with a 31% relative reduction from 1991 to 2018 [1]. However, cancer remains one of the leading causes of mortality worldwide. It is the second most common cause of death in the USA. According to the American Cancer Society estimates, approximately 5200 new cancer cases are diagnosed every day in 2021, and around 1600 daily deaths are linked to cancer [1, 2]. The decline in death rate is attributed to better screening, novel treatment therapies, and decreased smoking. On the other side, cardiovascular disease (CVD) not only claims most lives in the USA and globally, but it is also the primary cause of death in cancer patients and survivors [2, 3]. According to a study of 7.5 million cancer patients, 5% percent of patients died of CVD [3]. Cancer and CVD often co-exist, share multiple risk factors, and contribute significantly to population morbidity and mortality. As a result, the field of cardio-oncology has evolved to care for cancer patients at the interface of cancer and CVD. While there have been numerous advances in cardio-oncology, the disparities of health care in this patient population are relatively under-addressed.

This article provides a comprehensive review of the available data on disparities in cardio-oncology and the role of social determinants; we also identify the gaps in the literature and areas of research and suggest strategies to reduce inequities in this unique subset of patients (Fig. 1).

Fig. 1
figure 1

Contributory factors for disparities in cardio-oncology and the suggested interventions to address these disparities

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Social Determinants of Health and Disparities: Distinct but Inter-connected

Disparities in healthcare are interconnected with social determinants of health (SDOH). SDOH are the circumstances in which people are born, grow, live, work, and age [4]. The Center of Disease Control divides the SDOH into five sections: 1) Economic Stability, 2) Education access and quality, 3) Healthcare access and quality, 4) Neighborhood and built environment, 5) Social and community context [4]. The World Health Organization released the landmark report in 2008, which provided concrete evidence of the impact of SODH on health status and laid out approaches to tackle the inequitable distribution of healthcare resources, living conditions, and gender disparities [5].

Several studies on patients with CVD and heart failure (HF) have demonstrated the adverse impact of healthcare disparities on outcomes. As a result, both the American College of Cardiology (ACC) and American Heart Association (AHA) have issued statements addressing the SDOH in CVD and HF providing interventions to address socioeconomic profile, healthcare coverage, health literacy, and ethnic and racial disparities. [6, 7]

Similar to cardiology, the role of SDOH in the risks, rates, and survival of multiple cancers is increasingly emphasized, and efforts are directed to address them [8, 9]. American Cancer Society has recently released a framework of practice, research, and policy to better recognize and address the SDOH in cancer [8]. The Society aims for a 40% reduction in cancer mortality by 2035 (from 26% in 2015) and recognizes that interventional measures would have to be applied equitably [10].

Emerging evidence suggests that, similar to the cardiology and oncology patient population, SDOH play a vital role in the health of cardio-oncology patients. Our (unpublished) cross-sectional study using the CDC Wide-Ranging Online Data for Epidemiologic Research (WONDER) database and county-level social vulnerability index (SVI) data demonstrates that age-adjusted mortality rate (AAMR) for concomitant CVD and cancer was higher across age, sex, race, and urbanization, in counties with greater social vulnerability. Similarly, AAMRs for CVD and cancer were significantly greater in the highest socially vulnerable counties. However, the proportional increase in comorbid cancer and CVD-related mortality between the highest and lowest SVI counties was more significant than that observed for either CVD or cancer-associated mortality alone.

Disparities in Cardio-oncology

Racial and Ethnic Disparities

Race and ethnicity play a crucial role in cancer incidence, rate, and outcomes in the USA [11]. African-American (AA) patients have the highest mortality rates from all cancers combined compared to all other races and ethnicities in the USA [12]. AA men and women, American Indian men & women, and Asian/Pacific Islanders men have lower five-year survival rates compared to their non-Hispanic White counterparts [12]. Cancer is the leading cause of death in Hispanics/Latinos. Compared to non-Hispanic Whites, Hispanics are less likely to be diagnosed with cancer at an early stage [13].

Similar to cancer incidence and mortality, there are disparities in the development of cardiotoxicity among different races. AAs had a three times higher risk of developing cardiotoxicity with doxorubicin compared to non-AA patients in a study of 100 patients [14]. Childhood cancer survivors of African ancestry receiving cardiotoxic therapies had an increased risk of cardiomyopathy than those with European ancestry [15]. In a small study, AA patients had a higher risk of developing cardiotoxicity with trastuzumab than White patients and received incomplete cancer therapy as a consequence [16]. Another larger study on trastuzumab-related cardiotoxicity showed that AA women had a higher prevalence of risk factors for CVD. The risk of cardiotoxicity was significantly higher in AA women compared to White women even after controlling for cardiovascular risk factors [17]. Our study found that Asian & Pacific Islanders and Hispanics had the highest relative increase in cardio-oncology mortality between the 4th and 1st SVI quartiles. Additionally, AA individuals had the highest CVD, cancer, and comorbid cancer and CVD-related mortality. This was observed even within the most socially vulnerable counties when compared to White individuals [18••].

Racial minorities are also underrepresented in clinical trials. In one trial assessing dexrazoxane's cardioprotective effects in pediatric sarcoma patients receiving doxorubicin, the participation of AAs was 11% in the control arm and 13% in the intervention arm, Hispanics were 5.6% and 13%, and Asians were 5.6% and 0%, respectively [19]. In another trial of dexrazoxane in anthracycline toxicity, 6% of the control group and 8% of the intervention group were AAs, with other minority races comprising 1% and 2% of the control and dexrazoxane groups, respectively [20]. Similarly, in more contemporary imaging-based guidance for cardioprotective therapy initiation clinical trial—Strain Surveillance of Chemotherapy for Improving Cardiovascular Outcomes [SUCCOUR], only 2% of AAs participated [21]. Time and again, historical and contemporary research studies demonstrate that underprivileged race and ethnic groups are under-represented, highlighting the need to achieve equity in trial participation.

Sex-based Disparities

There are known sex-based disparities in both cancer and CVD. Women have been traditionally under-represented in clinical trials. There are differences in the representation of women between trials that reported statistically significant findings versus those that did not, with fewer women in significant trials [22]. The importance of improving representation and demographic reporting has been echoed by national organizations, yet these disparities persist. Women have been shown to receive less intense CVD medical therapy as well as less lifestyle counseling compared to men [23]. Similar disparities exist in cardio-oncology. Although male sex is thought to be an important risk factor in the development of cardiomyopathy, secondary to higher apoptosis-related protein expression [24], in a study of patients treated with anthracyclines, women were at higher risk of cardiac dysfunction than men [25]. A systematic review assessing cardiovascular mortality following radiation therapy for Hodgkin's lymphoma found that cardiovascular events and mortality were four times higher in women compared to men [26].

Disparities in Healthcare Access and Quality

Cancer survivors have been shown to have difficulty accessing healthcare. In a study of 30,364 cancer survivors from the National Health Interview Survey (NHIS), cancer survivors were more likely to report delayed care, forgo medical care, and be unable to afford medications when compared to control respondents [27]. Healthcare access disparities were recognized and explained for minorities, including Blacks, Hispanics, Asians, and Native Americans, compared to the White population in the landmark report of the Secretary's task force on "Black and Minority Health" in 1985. Cancer and CVD were reported as the top two of the six causes of excess mortality in the Black population compared to the White [28]. In 2002, 13.9% Whites, 16.7% AAs, 30.8% Hispanics,15.9% American Indians, and 18.5% Asians were without any source of medical care in the USA [12]. In a study of 3,135 USA counties, low-income counties had a more non-Hispanic Black population, reported poor health, and high rurality rates with a significantly higher cancer death rate in low-medium income counties than high-income counties [29].

A recent study of 149 patients at a safety net hospital undergoing chemotherapy with trastuzumab and/or doxorubicin with 46% Blacks, 27.5% Whites, and 22% Hispanics reported that all populations received the same level of surveillance and treatment, leading to similar outcomes for cardiotoxicity regardless of the race even though White patients were more likely to live in high-income areas [30]. Thus, it is possible to attain equitable outcomes even in underprivileged populations with accessible healthcare.

Disparities in Financial/Economic Stability

Economic stability and healthcare access go hand in hand and unfortunately are tied to racial marginalization. In a study comparing financial toxicity in individuals with atherosclerotic cardiovascular disease (ASCVD), financial toxicity was higher in ASCVD patients than cancer, with an even higher burden in the cardio-oncology population [31]. According to the interview-based survey of 1556 cancer survivors, 32% had financial problems, and those survivors were more likely to forgo medical care and prescription medications when compared to the survivors without financial issues [32]. Another study from five geographically distinct Veterans Administration Hospitals found that 48% population reported difficulty managing with their household income after a median of 7.3 years from cancer diagnosis (89% cancer-free and 11% with advanced cancer), and a high financial burden was associated with poor quality of life [33].

Low income is also related to the probability of being uninsured which has been linked with adverse health outcomes. AAs and Hispanics are much more likely to be uninsured than non-Hispanic Whites [34]. Medicaid insurers had lower cardiovascular mortality compared to uninsured, regardless of the type of cancer in one study [35]. Public insurance or no insurance has shown to be independently associated with progressively higher odds of advanced-stage disease for nearly all cancer types [36]. Another study demonstrated that uninsured young adults more commonly presented with metastatic disease, less commonly received definitive cancer treatment, and more commonly died from all causes [37]. A childhood cancer survivor report of patients at risk of cardiomyopathy showed that higher-income areas had higher rates of screening with echocardiograms than lower-income areas [38]. Similar results were noted in a different study with higher referral rates to cardio-oncology clinics from higher-income quartile groups [38].

HF is a common manifestation of antineoplastic therapy-associated cardiotoxicity. Patients with HF in lower and middle-income (LMIC) countries are less likely to receive guideline-directed medical therapy (GDMT) as compared to high-income countries. Only 15% of the patients with HF from LMIC were on GDMT 6-months after discharge. Women and patients without health insurance were least likely to be on GDMT [39].

The importance of financial strain and economic stability has been increasingly recognized, and there is a growing focus on addressing the issue. Enhancing survivorship care was one of the ten identified priorities to advance cardio-oncology care by the global cardio-oncology summit in 2019 [40•].

Disparities based on Neighborhood and Rurality

Striking differences exist in the rural and urban populations that affect healthcare access and quality of life. In a study of 6,003 HF patients, rurality was associated with fewer emergency department visits and an increased risk of death [41]. Another study followed 81,418 patients with solid organ cancers and baseline CVD in a Canadian Province for at least one year where rurality, low income, and low education were associated with higher odds of developing new CVD [42]. Rural patients with cancer have been shown to have worse outcomes than their urban counterparts. According to a recent report, the age-adjusted rate of cancer deaths in rural areas from 2011 to 2015 was 180.4 per 100 000 individuals, compared to 157.8 per 100 000 individuals in metropolitan areas [43]. However, according to SWOG (Southwest Oncology Group) trials, enhancing access to uniform treatment strategies for patients with cancer can aid in reducing the disparity in cancer outcomes between rural and urban patients [44].

Our study found that the mortality rate was higher for patients with comorbid cancer and CVD (cardio-oncology population) in the rural counties than their counterparts, regardless of the social vulnerability index [18••]. This highlights that even in relatively lower socially vulnerable parts of the country, people living in the rural counties, especially those with comorbid cancer and CVD, are more vulnerable and may have suboptimal outcomes.

Disparities and the Role of Environmental Factors

Many cardiovascular conditions and cancers stem from a complex interplay between genetic predisposition and environmental influences. While genetic factors are non-modifiable, environmental influences are highly modifiable and significantly impact how these diseases manifest. The human environment is an amalgamation of two domains—personal and social, which independently predict cardiovascular outcomes [45]. The personal domain comprises physical activity, nutrition, and smoking. 47% of stroke in women and 35% in men have been attributed to poor lifestyle choices [46, 47]. In a cohort of Swedish women, a healthy lifestyle was associated with a 92% decrease in myocardial infarction [48]. The social domain predominantly involves environmental pollution and socioeconomic status. Globally, air pollution is attributed to 7 million deaths/year, most of which are due to CVD [49]. Despite lesser air pollution and climate changes in the rural compared to metropolitan areas, rurality has been associated with worse outcomes as shown by various studies mentioned above. This paradoxical effect highlights how multiple factors and their complex interplay determine outcomes in cardio-oncology patients. Environmental toxins have also been implicated to play a role in various cancers and their progression like breast cancer [50]. Socially vulnerable populations usually suffer the most from climate impacts. They are often the least responsible for crisis and least able to protect themselves from consequential adversities.

While the environmental factors play an established role in both CVD and cancer, there is a dearth of data regarding cardio-oncology patients and remains an interesting area for future research.

Tools and Resources to Measure Social Determinants of Health

Various tools and resources are available to measure SDOH and hence disparities, including mapping tools and indices to measure social determinants based on geographical location. Examples of commonly used indices in the USA include the social vulnerability index [51] (SVI), area deprivation index [52] (ADI), and social deprivation index [53] (SDI). Table 1 illustrates the description of these indices, their uses, and their limitations.

Table 1 Commonly used indices to measure social determinants of health, their uses, and limitations in USA
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While SVI, SDI, and ADI are more commonly used, other indices are also available and used in the USA. Outside of the USA, a myriad of indices is available to track the socioeconomic status of communities and their progress and vulnerabilities in the context of the healthcare system's performance. Examples include the European deprivation Index (EDI) in many countries across Europe[54], socioeconomic disadvantage index (SEDI) and socioeconomic advantage index (SAI) in Singapore [55], NITI Aayog index in India [56], and the Chinese General Social Survey (CGSS) in China [57].

COVID-19 and its Impact on Disparities in Cardio-oncology

The COVID-19 pandemic has had a remarkable effect on the cardio-oncology population. Patients with active chemotherapy are at increased risk of exposure to COVID-19 and have worse outcomes if infected [58]. Patients with either cancer or CVD are established to have a higher likelihood of adverse events with COVID-19 [59]. In a retrospective study by our group, patients with a history of both cancer and CVD were noted to have a higher risk of experiencing COVID-19-associated adverse outcomes such as the need for mechanical ventilation, shock, or death as compared to patients with cancer or CVD alone [60•]. Similarly, of 8,222 hospitalized COVID-19 patients from AHA's cardiovascular disease registry, a history of cancer was a predictor of in-hospital mortality, and recent chemotherapy was associated with poor survival [61]. Frighteningly, due to various restrictions of the pandemic and apprehension about COVID-19, patients are also at increased risk of delay in cancer diagnosis, treatment, and routine healthcare visits. A study of 17 cancer centers in France reported up to a 21% decrease in patients managed with newly diagnosed cancer during the pandemic [62].

The pandemic has had a devastating effect on the economy, and healthcare delivery around the globe and socioeconomically disadvantaged populations have been disproportionately affected. A review of 42 studies reported that SDOH are associated with COVID-19 incidence, hospitalization, and outcomes, with strong evidence that race/ethnicity and socioeconomic deprivation were associated with an increased likelihood of COVID-19 incidence and resulting hospitalization. However, evidence on the effect of occupation, education, and housing was limited [63]. A study of 212 young adult cancer survivors during the COVID19 pandemic showed that 71% of the participants had at least one medical cost-coping behavior, such as skipping or delaying treatment [64].

The International Cardio-Oncology Society (ICOS) has issued a statement on cardio-oncology care in the COVID-19 pandemic with strategies to minimize the risk of COVID-19 implications in cancer patients with CVD, including expanding the use of cardiac biomarkers to screen for cardiotoxicity rather than cardiac imaging and use of telehealth [65]. Telemedicine (including E-consults, telephone, and video consultations) can also be used as an opportunity to enhance access to health care in remote areas lacking cardio-oncology services. Such measures, in the long run, could help break some of the social barriers and bring more equitable cardio-oncology care to vulnerable communities worldwide.

Opportunities for Improvement

  1. 1.

    Targeted Policy Intervention and Resource Allocation

    Patients afflicted with a dual diagnosis of cancer and CVD are highly vulnerable to disparities leading to adverse outcomes in this population and thus require special attention and equitable access to quality preventive, diagnostic, and therapeutic services. To attain healthcare equity, we need to realize the importance of achieving vertical (greater healthcare use by those with greater needs) and horizontal (equal healthcare use by those with equal needs) equity at the community level, which would require investment in healthcare infrastructure in socially vulnerable areas.

    While it is clear that health outcomes in marginalized communities are worse, the required steps to attain equity and optimal outcomes are not clear. Policymakers and community leaders should recognize that one size would not fit all, and policies must be tailored to the community's needs. Merely physical access to quality healthcare is not adequate. Our study demonstrated that while the mortality rate in the cardio-oncology population was worse in rural counties across the social vulnerability quartiles, the graded increase in mortality across SVI quartiles was not different based on the rural-urban divide, and the outcomes were worse in more socially vulnerable counties even if they were in urban or semi-urban locations [18••]. Thus, mere proximity of the high-quality healthcare facility may not solve the problem as there are many other dimensions to barriers to access. To reduce the disparities in health outcomes, we need to utilize public health resources in a targeted way to make healthcare more i) accessible, ii) affordable, iii) culturally acceptable, iv) and focused on community-based preventive care and well-being.

  2. 2.

    Increase Access to Cardio-oncology Care

    Despite increased awareness of the spectrum of cardio-oncology, the field is still growing. There are a limited number of cardio-oncology clinics and practicing physicians providing care to cancer patients with CVD. A national cardio-oncology survey of 444 adult and pediatric cardiology division chiefs and program directors conducted in 2014 showed that 39% of the participants did not feel comfortable taking care of cancer patients with CVD. 44% of respondents attributed the lack of funding and national guidelines as the most concerning roadblocks in developing a cardio-oncology program [66]. An electronic survey of general cardiology fellowship program directors in 2018 about the exposure to cardio-oncology in fellowship programs showed that 51% of the responder programs were a part of centers offering dedicated cardio-oncology services compared to 27% from a survey in 2014. Similarly, less than 10% of the cardiovascular training programs provide focused training in cardio-oncology [67].

    While dedicated training in cardio-oncology is emerging, it is limited to a small number of highly specialized centers. Most patients with cancer are cared for by community-based practices and cardiologists without specialized training. It is thus important to provide necessary knowledge pertaining to this patient population during cardiovascular disease fellowship training [68]. Both cardiology and oncology trainees, as well as practitioners globally, should be encouraged to participate in international meetings and workshops providing comprehensive education on various topics of cardio-oncology such as those organized by the ACC and ICOS to enhance the know-how of the subject and in turn access to quality care everywhere.

  3. 3.

    Inclusion of All Races in Clinical Trials

    Black adults and other racial minorities have been significantly underrepresented in the CVD trials [69] and oncology trials. For example, an analysis of global phase-1 trials of biopharmaceutical oncology agents showed that 62% of the participants were White. In the USA, 82.4% of the population was White, 7.3% were AAs, 3.4% were Asians, and 2.8% were Hispanic/Latinos and other races [70]. The underrepresentation of marginalized populations may undermine the generalizability of the trial findings and mask the heterogeneity of outcomes adverse events. Future trials should be designed to represent all racial and ethnic groups appropriately. This can be done by setting defined targets of enrollment of non-White minorities, increasing language adaptation of the education material, building community partnership for shared decision-making, and using patient navigators [71]. Additionally, clinical trials, if feasible, should be performed in multiple countries to ensure global diversity and not just diversity within the USA.

  4. 4.

    Utilization of Social Media to Increase Health Literacy

    Social media has a powerful impact on the audience and can increase health literacy in the general population and among physicians. This includes social networking sites such as Twitter, Facebook, Instagram, media sharing sites such as YouTube, and weblogs or blogs. These platforms are a relatively inexpensive tool that can increase the awareness of cardio-oncology among both healthcare providers and the public [72, 73]. Journal of American College of Cardiology: Cardio-oncology (JACC CardioOncology) social media ("SoMe") platform has received commendable responses [74]. An analysis of Twitter use for cardio-oncology from 2014 to 2018 during five major cardiology and oncology meetings showed that Twitter users increased 597% from 2014 to 2018. 73.5% of the total analyzed tweets were from physicians [72]. Social media platforms can be an essential promoter of public health if used correctly and within the guidelines provided by healthcare organizations and societies.

  5. 5.

    Integration of SDOH in Clinical Care Delivery

    The screening and documentation of SDOH in medical records can be an important driver to resolve health inequities. In a cross-sectional study of 4976 physician practices and 1628 USA hospitals from 2017 to 2018, 16% of physicians and 28% of hospitals reported screening for transportation needs, utility needs, housing instability, and food insecurity [73]. International Classification of Diseases, Tenth Revision, Clinical Modification codes (ICD-10 CM) has a subset of codes called Z codes (Z55-65) to document the SDOH in electronic medical records. A retrospective analysis of documentation of SDOH in electronic health records from 2015 to 2018 showed a low rate of utilization of ICD-10 CM-Z codes [75]. Underscreening of the SDOH is one of the reasons behind the under-utilization of these ICD codes. Some challenges to documentation include the high workload of physicians and lack of familiarity with Z-codes. This can partly be addressed if SDOH documentation is supported by nurses, case managers, physician assistants, and even patients interacting with their own electronic medical records to incorporate the data in their charts. In fact, AHA coding clinic's official guidelines on coding and reporting in 2018 officially allowed clinicians (including non-physician providers) to document the SDOH in the electronic record systems [76]. The availability of real-time data on SDOH will enable healthcare providers to identify vulnerable patients and provide actionable information at the point of care.

  6. 6.

    Opportunities for Research

Realization and recognition of the magnitude of a problem are the first step toward its elimination. There are limited data on disparities that exist in cardio-oncology and how they affect patient care and outcomes providing innumerable research opportunities. This can be divided into the individual, interpersonal, organization, and national levels as summarized in Table 2.

Table 2 Various levels of research and suggested research questions to understand the impact of disparities in cardio-oncology and develop strategies to mitigate
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Big data can be an invaluable tool in research related to health inequities. Zhang et al. explained how big data science offers multiple opportunities to reduce health disparities and improve minority health [77]. These include the incorporation of insurance, demographics, and SDOH information in electronic medical records. Big data can also be used to improve public health surveillance and monitoring and cannot only identify the disparities but also help track the trends in these disparities and their effects on patient outcomes.

Future Directions

While our understanding of disparities, the role of various social determinants, and their crucial interplay with an individual's health has increased, it is primarily based on retrospective and aggregate data. Prospective data on how such disparities impact an individual's health and outcomes of various investigational and established cancer and CVD-related health interventions are lacking. To study these issues at a granular level, which will help us take targeted and pragmatic actions to reduce the disparities, we need to integrate various individualized SDOH parameters in prospective clinical trials and registry data collection.