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Societal factors rather than genetics might drive disparities in cardiovascular disease (CVD) outcomes among individuals who self-identify as Black. A study in JAMA Cardiology found no significant associations between West African ancestry and blood pressure (BP), kidney function, and left ventricular mass changes in response to antihypertensive therapy. While the use of race in cardiovascular research may need a reevaluation, some experts say it would be beneficial to improve upon genomic data on Black lineage.

Genetics are often grouped with societal, behavioral, and environmental factors as catalysts for disparities of self-identified races. “Because racial identity itself is a social rather than biological construct, it is vulnerable to confounding because of the effects of structural racism, socioeconomic inequality, environmental disparities, and unequal access to care, limiting its interpretability,” wrote the investigators.

Black individuals in particular suffer disproportionately from CVD problems such as hypertension and BP control. Studies of genetic and biological contributing factors in disparities in care haven’t done a robust job of addressing societal and environmental factors.

“We wanted to better understand what drives these differences, because Black Americans are known to face more social barriers to accessing healthcare,” Shreya Rao, MD, MPH, a research fellow at UT Southwestern Medical Center in Dallas and the study’s first author, told CLN Stat. The Systolic Blood Pressure Intervention Trial (SPRINT) offered a unique opportunity to study this question, “as all participants had similar access to providers and therapies during the study period, and all were placed on similarly aggressive protocols to achieve BP control,” said Rao.

Trial investigators recruited 2,466 individuals who self-identified as Black and had elevated risk for CVD events and hypertension. The goal: to assess the proportion of West African genetic ancestry in response to antihypertensive medication, BP control, and CVD outcomes. West African ancestry proportions ranged from 30% to 100%. Recruitment took place from 2010 to 2015, and analysis of the data occurred in 2020. Investigators genotyped 106 biallelic ancestry informative markers to develop West African ancestry proportion and used linear mixed-effect modeling to assess BP and kidney function across tertiles of genetic West African ancestry proportion, in the trial’s follow-up stage.

Multivariable adjusted Cox models evaluated any link between West African ancestry and risk of CVD events such as heart failure, death, and nonfatal myocardial infarction (MI).

Overall, the investigators found an association between a higher proportion of West African ancestry and moderately lower risk for CVD, after adjusting for potential confounders. Increasing West African ancestry proportion was associated with higher high-density lipoprotein cholesterol levels, higher rates of never smokers, and lower rates of Framingham Risk Scores. Baseline BP didn’t vary much across increasing tertiles of West African ancestry. Other metrics such as proteinuria, serum creatinine, and prevalence of left ventricular hypertrophy rose with increasing West African ancestry, although estimated glomerular filtration rate decreased.

Over time, however, the researchers did not find any significant differences in long-term trajectories of BP, kidney function changes, and left ventricular mass across tertiles of West African ancestry proportion. “There was no difference in the number of antihypertensive agents required to achieve target BP control across the West African ancestry distribution,” reported the study authors. Self-identified Black participants at all proportions of West African ancestry were able to achieve BP control over 4 to 5 years of follow-up.

For these reasons, the researchers “conclude that nongenetic factors, such as differences in access to healthcare and therapies, likely drive the differences between Black and white individuals in real-world settings,” said Rao.

The findings indicate that self-identified race and genetic ancestry are not interchangeable risk factors, Rao continued. “Differences we observe clinically between self-identified racial/ethnic groups do not necessarily imply a genetic/biological difference.” The hope is this work will lead to a more thorough evaluation of racial disparities and a better understanding of race and ethnicity. As this field of research grows, the medical field should move away from the inexactness of using the social construct of self-identified race to a more precise and objective use of ancestry and genetics in understanding genetic risks, she added.

“This work is an important start to disentangling the role of ancestry from social determinants of health in race-based hypertension disparities,” Tiffany M. Powell-Wiley, MD, MPH, said of the SPRINT study in a related editorial. However, the historic lack of robust genomic data on African ancestry and U.S. individuals who self-identify as Black should be taken into consideration, she noted.

“Until recently, there was a paucity of genomic data on the populations across the African continent, which has limited our ability to account for the rich genetic variability of populations on the continent when inferring African ancestry,” wrote Powell-Wiley.

Diversifying genotypic data on this population is an important step forward, as genomic medicine progresses, she added. “The Human Heredity and Health (H3Africa) Consortium is an example of critical efforts in building genomic data resources and genomic research and training capacity on the continent, with a particular focus on CVD research.”

Community and academic partnerships are crucial in engaging vulnerable populations and enacting needed interventions, Powell-Wiley continued. “If we are to move beyond racial health disparities and toward health equity, we must continue taking steps in shifting the paradigm away from race as a potential determinant of CVD risk and toward social determinants of health,” she said.

In light of this study and commentary, it might be time to recalibrate the use of race in cardiovascular research, suggested the editors of JAMA Cardiology. Clyde W. Yancy, MD, MSc, and Elizabeth McNally, MD, PhD, proposed a model to sharpen genetic and social health determinants. “With genetic markers of ancestry, it should be possible to understand which genetic markers contribute to outcomes and ultimately develop better factors associated with cardiovascular health,” they wrote. “And for social determinants of health, many of these determinants, but not all, can be accessed from electronic health records.”

Yancy and McNally advocated for clinical trials to improve databases and help develop new genetic pathways “that would eventually obviate most references to race.” A more precise definition of genetic markers and social determinants will lead to more effective interventions on CVD disparities, they concluded.

Building upon their study results, Rao’s team plans to evaluate racial disparities in other aspects of CVD, such as heart failure, stroke, and MI. “We have partnered with multiple large cohort studies enrolling Black participants to continue building a body of work to better examine the role of genetic ancestry in these disease processes,” said Rao.