Race, Ancestry, and Risk: Targeting Prevention to Address Heart Failure Disparities

Introduction:

Race-based disparities in heart failure (HF) are greater than disparities in all other cardiovascular disease subtypes in the United States. There is an estimated 20-fold higher incidence rate of and a three-fold higher mortality rate due to HF in young Black adults compared with young White adults.¹ Addressing racial disparities in HF should begin before the manifestations of overt disease and requires multi-level interventions, including the need to address contributions of structural racism. Comprehensive risk assessment may enhance our ability to intensify prevention efforts in those at greatest risk for HF. Importantly, this must start with the acknowledgement that race is a social construct and not a biological one.² With that foundational understanding, this perspective discusses the value of multivariate risk prediction, contextualizing social factors that reclassify risk, and integrating and expanding knowledge on genetic variants for HF in diverse populations to develop a comprehensive approach towards equitable prevention of HF.

Traditional Risk Factors:

The foundation of our preventive efforts must begin with addressing traditional HF risk factors. Black Americans have among the highest rates of hypertension in the world.³ Once diagnosed, Black patients have lower prevalence of control. The reasons for the higher rates of suboptimal control are complex and interrelated and due primarily to social, environmental, and behavioral factors.⁴ Equitably targeting intensive blood pressure (BP) lowering in those at high HF risk will be imperative to reduce disparities in HF. Risk equations that have been validated in diverse cohorts, such as the Pooled Cohort Equation to Prevent Heart Failure (PCP-HF), may help identify individuals at high risk of HF.⁵ These risk equations include race-specific coefficients for variables such as age, sex, cholesterol levels, BP, diabetes status, and smoking status. Because race is a social construct, it was not used as a covariate and should not be treated as causative. These race-specific models were derived based on self-reported race, but future models that remove race and focus on other variables reflecting social determinants of health (e.g., insurance status, educational attainment, or zip code) are needed. Root causes of health disparities in HF risk factors are due to disproportionate exposure to adversity (including overt racism) and other barriers to care. These are socially mediated burdens and not due to race as a monolithic risk factor. Through greater understanding of these factors can optimal and personalized preventive interventions be taken to mitigate HF disparities.

Integrating Social Determinants:

While risk of HF is largely related to modifiable risk factors, this risk is potentiated by the confluence of adverse social factors experienced by minoritized individuals (e.g., social determinants of health). In the US, anti-Black racism shapes these forces such that Black Americans, structurally, have a higher burden of detrimental social determinants.⁶ A variety of SDoH (e.g., low educational attainment, low annual household income, zip code poverty, poor public health infrastructure, and lack of health insurance) have been associated with incident HF.⁷ These must be addressed to adequately address HF risk. Based on literature demonstrating associations between self-reported experiences of unfair treatment and hypertension, it reasonable to infer that racism and bias may impact HF risk. These data portray the multifactorial nature of HF risk and highlight that structures, not biological differences, are the primary drivers of risk.⁸

Ancestry and Genetics:

It is well-established that both environmental and genetic risk factors contribute to risk of HF.⁹ Heritability estimates for HF range from 26% to 34% and there are an increasing number of genetic variants identified to be associated with HF. The advent and rapid development of sophisticated large-scale genetic sequencing has fueled important discoveries in HF biology, but this work has been conducted in populations predominantly of European ancestry. This is challenging as lack of diversity in available genetic data hampers understanding of genetic drivers of risk. For example, a common variant in transthyretin, V122I affects approximately 4% of individuals of African ancestry.¹⁰ This variant is associated with more than a 2-fold higher risk of HF, but a novel therapy that targets the transthyretin protein is available. Hence, there is a pressing need to expand the size and number of studies involving those of African ancestry to identify genetic risk factors for HF that may be unique to this ancestral group.

However, it is important not to conflate ancestry and race; the former specifically relates to genetic population structures that are correlated with biogeographic origins, and the latter is a social construct used to categorize individuals within a population. Race is therefore imbued with other sociocultural and political factors, biases, and racism. Investigators who study genetic associations in diverse populations must be cognizant of how their findings are presented and interpreted. They should be cautious to ensure that their findings are not used erroneously and maliciously to support supremacist agendas, as has happened in the past.

Charting the Path Forward:

How should these data inform research and clinical practice (Figure)? First, we must be relentless in our mission to dismantle the ubiquitous systems of racism. Second, we must redouble our efforts to enhance risk communication and focus on improving implementation of evidence-based strategies for our Black patients at greatest risk of HF. We can also engender trust by further diversifying our physician and non-physician workforce (e.g., clinical pharmacists, advanced practice practitioners). More effective workforce utilization could include transitioning care from the clinic or hospital setting into the home (e.g., home BP monitoring).¹¹ We should, moreover, expand our definition of the classic healthcare team to include community health workers. Together, we should prioritize meeting patients where they are and providing comprehensive risk factor modification that incorporate SDoH.¹² Once risk is relayed, we should consider disruptive approaches to mitigate these disparities in risk. Approaches to consider include embedding interventions in community settings like the barbershop,¹³ employing different delivery strategies such as fixed-dose combination drug therapies,¹⁴ and altering policies to support healthier dietary patterns like DASH and plant-based diets. In addition, policies to increase health care access and affordability are needed.

Recommendations for Addressing Race and Risk in Heart Failure.

Summarized in the figure are key recommendations, considerations for potential policy recommendations, and potential clinician-level impact.

SDoH: Social Determinants of Health

Conclusions:

As comprehensive risk-based strategies increasingly incorporate multi-dimensional risk associated with race in the US, we may be able to mitigate disparities in HF that exist by earlier identification and intervention. Quantification of HF risk should account for adverse social factors that enhance risk and highlight the unique risk borne by Black adults due to structural racism. Strategies to target risk will need to include community-engaged approaches and advocacy for policy changes to equitably promote cardiovascular health. While we are dismantling the systems that perpetuate racial disparities, we must acknowledge their existence and integrate this into our actions for equitable prevention of HF.