Anthracyclines, a mainstay of cancer chemotherapy, have been known to induce cardiotoxicity.1,2 However, data are lacking on anthracycline cardiotoxicity in racially and ethnically diverse populations.  

A research team at the American Heart Association (AHA) Scientific Sessions 2021, held virtually from November 13 to 15, 2021, presented new data on anthracycline cardiotoxicity in a multiracial community. In the study, “Racial and Ethnic Differences in Anthracycline Cardiotoxicity,” researchers examined Black, Hispanic, Asian, and White cancer survivors with incident heart failure, who had received anthracycline-based chemotherapy for any type of cancer in 2016 and 2019.3

Notably, a majority of the patient population was from the Bronx, New York, which has a predominantly Hispanic (54.8%) and Black (28.5%) population, according to 2020 US Census Bureau data for NYC boroughs.4 As recent research indicates, Black and Hispanic individuals are still underrepresented in cancer clinical trials.5


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To gain more insights on the AHA research indicating racial and ethnic disparities in anthracycline cardiotoxicity, we spoke with one of the study authors, Carlos J Rodriguez, MD, MPH, FACC, FAHA, a professor of medicine and epidemiology and population health, vice chair of academic affairs, and director of clinical cardiovascular research and cardiovascular epidemiology at Albert Einstein College of Medicine and Montefiore-Einstein Center for Heart & Vascular Care.

What data were available on anthracycline cardiotoxicity in racially and ethnically diverse populations before your team’s research?

Dr Rodriguez: There’s some prior data suggesting that there are racial and ethnic differences in cardiotoxicity, but they’re very limited. 6,7 Some of that prior data did suggest that there were higher cardiotoxicity rates among Black cancer patients7… But, as I said, most of that data was from older studies. One of the studies was almost 2 decades old. The sample sizes were small. The databases did not have important characteristics, such as socioeconomic factors, and the data in those studies was mostly inclusive of [Black and White individuals] with little to no data on [Hispanic and Asian individuals]. So we, obviously, wanted to do a larger, more diverse and contemporaneous study to look at this issue.

Per your study data, the cumulative incidence of heart failure was 23% in Asian cancer survivors treated with anthracycline the highest among all racial and ethnic groups. What may be contributing to this statistic?

Dr Rodriguez: So, obviously the problem is that when cancer patients are exposed to some cancer drugs and, in this case, particularly, anthracycline, those drugs even though they’re treating the cancer, they could affect the heart and lead to the heart getting weaker and for heart failure to be manifested. It can happen with different types of cancers, since different cancer drugs are used to treat [various] types of cancer, and different cancer drugs have [varying] levels of risk. Some have higher risks [that] affect the heart. We chose to study anthracycline for this study. That’s one of the cancer drugs that has known cardiac effects, or can weaken the heart. What we found is that Black and Hispanic patients had a higher incidence of heart failure at any point following anthracycline treatment. We did see that there was a higher incidence when it came to all of the groups.

There was a higher incidence, even among Asian cancer survivors, and those findings were interesting and intriguing, but not really conclusive in any way. The Asian receptive group in this study — and our sample was very small — was 10-fold smaller than any of the other groups. So, we cannot be fully confident in the validity of the signal, but the higher incidence of heart failure among Asian cancer survivors — and it was higher than what was seen in [Black, Hispanic, or White individuals] — does highlight an important point: That is that Asian individuals are underrepresented in this field of study, and this group needs to be further studied in this regard.

Since the study’s sample size of Asian participants was very small, should we be more focused on the data regarding Black and Hispanic individuals?

Dr Rodriguez: Yes, I think that that is the main result, the main point of this study. We show higher risk factors, lower socioeconomic status among [Black and Hispanic patients] compared to [White patients]. And even after adjusting for these factors, [Black and Hispanic patients] had a higher incidence of heart failure at any point following treatment with anthracycline chemotherapy.

I think that’s the main finding. Again, the signal among Asian individuals was surprising … , but I think the main purpose of that signal, even though we cannot be fully confident in [its] validity, … is that this group needs to be further studied.

In the study, hypertension, diabetes, and hyperlipidemia were highlighted as being more prevalent in Black, Hispanic, and Asian patients, but not in White patients. Do you believe that cultural differences in daily habits may play a role?

Dr Rodriguez: Yes, I think that there could be some cultural differences. Some of the main cultural differences would be in diet. …[I]t’s already known that [Black and Hispanic individuals] carry a higher burden of heart failure risk factors than [White individuals]. [Black and Hispanic individuals] have higher rates of hypertension, diabetes, dyslipidemia, and obesity. This has been shown in … multiple other works of literature by other researchers. So, I think that we already know that these differences exist and the higher prevalence of these risk factors among [Black and Hispanic patients] is due to a multitude of factors that happen at a patient level, at the healthcare system level, and at the environmental level.

So, it’s not just at the cultural level. You have different factors, different social determinants of health, and factors of structural racism … that have led to these cardiovascular health disparities that you see manifested in our dataset of our inner city population.

 Could you please elaborate on the social and environmental factors that contribute to cardiovascular health disparities?

Dr Rodriguez: Well, you have structural racism and social determinants of health that are the fundamental drivers of some of the health inequities that we see in this dataset. These health inequities can impact some of the results that we see with anthracycline cardiotoxicity in many ways. You have health inequities that are linked to an increased prevalence of heart failure risk factors and poor control of these heart failure risk factors, so poor hypertension, blood pressure control, or worse control of diabetes among [Black and Hispanic patients], predisposing these groups to cardiotoxicity. You have health inequities in access to care, in access to specialized care. You have lack of insurance … and also health inequities that lead to a more stressful experience among cancer patients. Cancer is already a stressful experience enough, but when you have factors like poverty, lower household income, financial and food insecurity, lack of health literacy, and worse quality of patient-provider interactions, all of these things lead to the heart effects that we’re seeing.

There may be also differential treatment, which we have not yet explored in this dataset. Also, when you talk about environmental aspects and social determinants of health, there [are] food deserts, or the lack of healthy food available in poor inner city neighborhoods, which is one of the main factors contributing to some of the cardiac effects that we see.

What can cardiologists do to increase awareness about these racial and ethnic disparities in anthracycline cardiotoxicity?

Dr Rodriguez: I think it starts with awareness and acceptance, being cognizant that these racial and ethnic differences and inequities do exist throughout other areas of medicine. It’s documented already … , but I think understanding that these differences and inequities extend into the cardio-oncology arena [is also important]. AHA has published a statement on the role of structural racism in cardiovascular disease.8 I think that statement … is a great starting point for us all to become more aware of these inequities. Increasing awareness is the first part. And then once awareness is increased, then we have to act accordingly to try to do our part in addressing these inequities.  

Should physicians ­­ specifically cardiologists, primary care physicians, and oncologists be managing these patients differently? If so, how?

Dr Rodriguez: Well, our work highlights that the Black, Hispanic, and Asian population are at a higher risk for these cardiovascular adverse events from chemotherapy, particularly anthracycline. So yes, these populations, in my opinion, need more attention in this regard. As physicians, we should give special attention to these populations with more aggressive optimization and control of these risk factors, possibly more frequent cardiac monitoring during cancer treatment, and also the understanding that there’s a higher risk. So, it should … further emphasize that cardiologists and oncologists along with primary care providers need to work together as a team [in the] cancer treatment [care] process of these patients to avoid or at least minimize the cardiotoxicity complications that we’re seeing in these populations.

What steps have you taken in your practice to help address these racial and ethnic disparities?

Dr Rodriguez: My practice is predominantly Black and Hispanic. In my patients, I make it a point to make sure that cardiac risk factors are optimized and aggressively controlled, particularly before these patients undergo cancer treatment [and] definitely during cancer treatment — anything that can be done from a preventative [standpoint] to avoid the manifestation of cardiotoxicity or heart failure. I think monitoring is also important [in these high-risk populations]. So, if monitoring and then treating accordingly, we’ll be able to see signs of cardiotoxicity or heart failure develop in this group.

Also, among the Asian population and the Hispanic population, there may be increased use of certain complementary and alternative medicines that can interact with cancer therapies that can affect some of the results we’ve seen. So, I think an honest discussion with these [patient groups] about what other alternative treatments or medicines they may be using during the cancer process is important to have because these types of practices are common among the Hispanic and Asian population.

References

  1. Cardinale D, Iacopo F, Cipolla CM. Cardiotoxicity of anthracyclines. Front Cardiovasc Med. Published online March 18, 2020. doi:10.3389/fcvm.2020.00026
  2. Gabani M, Castañeda D, Nguyen QM, et al. Association of cardiotoxicity with doxorubicin and trastuzumab: a double-edged sword in chemotherapy. Cureus. Published online September 22, 2021. doi:10.7759/cureus.18194
  3. Zhang L, Song J, Clark R, et al. Racial and ethnic differences in anthracycline cardiotoxicity. Presented at: AHA Scientific Sessions 2021; November 13-15, 2021. Abstract 13090
  4. US Census Bureau. NYC Decennial Census Data: City & Boroughs, Community Districts, 2020 NTAs, 2020 Census Tracts. Accessed November 30, 2021. https://www1.nyc.gov/assets/planning/download/office/planning-level/nyc-population/census2020/nyc_decennialcensusdata_2020_2010.xlsx
  5. Javier-DesLoges J, Nelson TJ, Murphy JD, et al. Disparities and trends in the participation of minorities, women, and the elderly in breast, colorectal, lung, and prostate cancer clinical trials. Cancer. Published online November 22, 2021. doi:10.1002/cncr.33991
  6. Al-Sadawi M, Hussain Y, Copeland-Halperin RS, Steingart RM, Johnson MN, Yu AF. Racial and socioeconomic disparities in cardiotoxicity among women with HER2-positive breast cancer. Am J Cardiol. Published online February 19, 2021. doi:10.1016/j.amjcard.2021.02.013
  7. Litvak A, Batukbhai B, Russell SD, et al. Racial disparities in the rate of cardiotoxicity of HER2-targeted therapies among women with early breast cancer. Cancer. Published online January 30, 2018. doi:10.1002/cncr.31260
  8. Churchwell K, Elkind MSV, Benjamin RM, et al. Call to action: structural racism as a fundamental driver of health disparities: a presidential advisory from the American Heart Association. Circ. Published online November 10, 2020. doi:10.1161/CIR.0000000000000936