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SPRINT: African Ancestry Not an Innate CVD Risk in Blacks

— Study refutes genetic basis for racial disparities in hypertension, CVD

MedpageToday
The African continent divided up by the country flags next to a young Black male

Genetics did not dictate worse outcomes for Black people in the SPRINT trial, supporting arguments against racial disparities in hypertension being hardwired in the genome.

Black-identifying individuals were divided into tertiles by proportion of West African ancestry and found to share similar longitudinal trajectories of blood pressure (BP), kidney function parameters, and left ventricular mass across the board, reported Ambarish Pandey, MD, MSCS, of University of Texas Southwestern Medical Center in Dallas, and colleagues.

What's more, every 5% increase in West African ancestry was associated with lower risk of composite cardiovascular events (non-fatal MI, cardiovascular death, and heart failure events) over an average 3.2 years (adjusted HR 0.92, 95% CI 0.85-0.99), Pandey's group reported online in . The study was also presented at this year's virtual American Heart Association conference.

"Hypertension affects nearly 1 in 2 Black adults, who additionally experience higher rates of severe, nocturnal, and nondipping phenotypes, as well as reduced responsiveness to standard BP regimens, contributing to notions of an innate biological risk associated with Black race," the authors noted.

"Although we cannot exclude the role of all genetic variants, our study findings highlight that the racial disparities in hypertension control and associated cardiovascular risk may not be predominantly associated with genetic factors and are more likely driven by ," they concluded.

The medical community is now beginning to see race as "what it has always been: a social construct," according to Tiffany Powell-Wiley, MD, MPH, of the National Heart, Lung, and Blood Institute of the NIH in Bethesda, Maryland, in .

"It is clear that systemic racism, or structural inequity defined by race, limits access to economic stability, quality health care, and safe, well-resourced environments, which are reflected in the social determinants of health for Black people in the U.S.," according to Powell-Wiley.

JAMA Cardiology editors Clyde Yancy, MD, and Elizabeth McNally, MD, PhD, both of Northwestern University Feinberg School of Medicine in Chicago, agreed: "race is a social construct."

"We dismiss any biological inferences that support the use of race, while we also recognize the importance of genetic ancestry. Given these considerations, it is time for a recalibrated use of race in cardiovascular research," they wrote in .

"Self-described race should not be used as shorthand to infer social determinants of health or signify genetic ancestry. Inclusion of genetic ancestry and explicit social determinants of health in clinical trials and registries will move science forward to match our increasingly diverse population and, if ideally executed, narrow persistent health disparities," Yancy and McNally argued.

SPRINT was a large trial in which participants 50 years and older with hypertension and elevated cardiovascular risk were randomized to intensive or standard BP control strategies.

For their post hoc analysis, Pandey and colleagues included 2,466 self-identified Black people in the trial.

Based on biallelic autosomal ancestry informative genetic markers, the overall cohort had a median 81% West African ancestry.

"In the U.S., individuals of self-identified Black race represent a convergence of predominantly West African and European geographic ancestries, with West African geographic ancestry heterogeneously distributed within the population. As a result, the measured proportion of geographic West African ancestry in this population can serve as a proxy for race-specific risks attributable to genetic factors, allowing for genetic risk to be directly measured in the population," according to study authors.

At baseline, people with more West African ancestry tended to have higher HDL cholesterol levels and lower Framingham Risk scores. They were more likely to report never having smoked and less likely to have insurance or a college education.

Pandey's team acknowledged the possibility of unmeasured and residual confounding in the study. Other caveats included the lack of ambulatory BP measurements and the authors' inability to conduct an analysis of U.S.-born vs foreign-born individuals.

Moving forward, there should be more efforts to diversify the available genotypic data in the journey towards genome-based medicine, Powell-Wiley urged.

Collecting genetic ancestry and accurately recording social determinants will add to the cost of conducting clinical cardiovascular trials, but the diversity of these trials could allow for a concerted data-gathering experience, Yancy and McNally suggested.

"Clinical trials represent a unique opportunity to build better databases and provide capacity to find new definitive genetic pathways that would eventually obviate most references to race," they wrote.

Powell-Wiley emphasized that researchers should not only identify specific biologic mechanisms by which social and environmental factors promote health disparities but also design multilevel interventions that promote systems-level changes for reducing hypertension disparities.

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    Nicole Lou is a reporter for 鶹ý, where she covers cardiology news and other developments in medicine.

Disclosures

Pandey has served on the advisory board of Roche Diagnostics and is supported by a Texas Health Resources Clinical Scholarship, the Gilead Sciences Research Scholar Program, and a National Institute of Aging GEMSSTAR grant.

Powell-Wiley disclosed receiving NIH grants.

Yancy and McNally had no disclosures.

Primary Source

JAMA Cardiology

Rao S, et al "Association of genetic West African ancestry, blood pressure response to therapy, and cardiovascular risk among self-reported black individuals in the Systolic Blood Pressure Reduction Intervention Trial" JAMA Cardiol 2020; DOI: 10.1001/jamacardio.2020.6566.

Secondary Source

JAMA Cardiology

Powell-Wiley TM "Disentangling ancestry from social determinants of health in hypertension disparities -- an important step forward" JAMA Cardiol 2020; DOI: 10.1001/jamacardio.2020.6573.

Additional Source

JAMA Cardiology

Yancy CW, McNally E "Reporting genetic markers and the social determinants of health in clinical cardiovascular research -- it is time to recalibrate the use of race" JAMA Cardiol 2020; DOI: 10.1001/jamacardio.2020.6576.