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 (SPRINT)

Rao, Shreya; Segar, Matthew W.; Bress, Adam P.; Arora, Pankaj; Vongpatanasin, Wanpen; Agusala, Vijay; Essien, Utibe R.; Correa, Adolfo; Morris, Alanna A.; Lemos, James A. de; Pandey, Ambarish

doi:10.1001/jamacardio.2020.6566

Cited by 31 publications

(26 citation statements)

References 43 publications

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“…Descriptive studies of African admixture in the US report marked variability in percentage African ancestry by geographic regions, with the highest levels of African genetic ancestry observed in rural southern states [ 23 ]. In most studies, adjusting for socioeconomic and lifestyle variables attenuates the relationship between African ancestry to non-significance [ 36 , 46 , 63 , 66 ]. For example, Non et al reported no evidence of an association between West African ancestry and hypertension following adjustment for education in a study of SIAA [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Relative impact of genetic ancestry and neighborhood socioeconomic status on all-cause mortality in self-identified African Americans

et al. 2022

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Self-identified race/ethnicity is a correlate of both genetic ancestry and socioeconomic factors, both of which may contribute to racial disparities in mortality. Investigators often hold a priori assumptions, rarely made explicit, regarding the relative importance of these factors. We studied 2,239 self-identified African Americans (SIAA) from the Prostate, Lung, Colorectal and Ovarian screening trial enrolled from 1993–1998 and followed prospectively until 2019 or until death, whichever came first. Percent African genetic ancestry was estimated using the GRAF-Pop distance-based method. A neighborhood socioeconomic status (nSES) index was estimated using census tract measures of income, housing, and employment and linked to participant residence in 2012. We used Directed Acyclic Graphs (DAGs) to represent causal models favoring (1) biomedical and (2) social causes of mortality. Hazard ratios were estimated using Cox models adjusted for sociodemographic, behavioral, and neighborhood covariates guided by each DAG. 901 deaths occurred over 40,767 person-years of follow-up. In unadjusted (biomedical) models, a 10% increase in percent African ancestry was associated with a 7% higher rate of all-cause mortality (HR: 1.07, 95% CI: 1.02, 1.12). This effect was attenuated in covariate adjusted (social) models (aHR: 1.01, 95% CI: 0.96, 1.06). Mortality was lower comparing participants in the highest to lowest nSES quintile following adjustment for covariates and ancestry (aHR: 0.74, 95% CI: 0.57, 0.98, Ptrend = 0.017). Higher African ancestry and lower nSES were associated with higher mortality, but African ancestry was not associated with mortality following covariate adjustment. Socioeconomic factors may be more important drivers of mortality in African Americans.

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Section: Discussionmentioning

confidence: 99%

Relative impact of genetic ancestry and neighborhood socioeconomic status on all-cause mortality in self-identified African Americans

et al. 2022

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“…[17][18][19]22 Genetic ancestry proportions have been previously noted to be associated with poor cardiometabolic phenotype and with adverse cardiovascular events. 23,24 Importantly, the relationship between the genetic ancestry proportion and incident diabetes among high-risk, hypertensive Black individuals has not been previously evaluated.…”

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confidence: 99%

Genetic European Ancestry and Incident Diabetes in Black Individuals: Insights From the SPRINT Trial

Parcha

Heindl

Kalra

et al. 2022

Circ: Genomic and Precision Medicine

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Background: Black individuals have high incident diabetes risk, despite having paradoxically lower triglyceride and higher HDL (high-density lipoprotein) cholesterol levels. The basis of this is poorly understood. We evaluated the participants of SPRINT (Systolic Blood Pressure Intervention Trial) to assess the association of estimated European genetic ancestry with the risk of incident diabetes in self-identified Black individuals. Methods: Self-identified non-Hispanic Black SPRINT participants free of diabetes at baseline were included. Black participants were stratified into tertiles (T1–T3) of European ancestry proportions estimated using 106 biallelic ancestry informative genetic markers. The multivariable-adjusted association of European ancestry proportion with indices of baseline metabolic syndrome (ie, fasting plasma glucose, triglycerides, HDL cholesterol, body mass index, and blood pressure) was assessed. Multivariable-adjusted Cox regression determined the risk of incident diabetes (fasting plasma glucose ≥126 mg/dL or self-reported diabetes treatment) across tertiles of European ancestry proportion. Results: Among 2466 Black SPRINT participants, a higher European ancestry proportion was independently associated with higher baseline triglyceride and lower HDL cholesterol levels ( P <0.001 for both). European ancestry proportion was not associated with baseline fasting plasma glucose, body mass index, and blood pressure ( P >0.05). Compared with the first tertile, those in the second (hazard ratio, 0.64 [95% CI, 0.45–0.90]) and third tertiles (hazard ratio, 0.61 [95% CI, 0.44–0.89]) of the European ancestry proportion had a lower risk of incident diabetes. A 5% point higher European ancestry was associated with a 29% lower risk of incident diabetes (hazard ratio, 0.71 [95% CI, 0.55–0.93]). There was no evidence of a differential association between the European ancestry proportion tertiles and incident diabetes between those randomized to intensive versus standard blood pressure treatment. Conclusions: The higher risk of incident diabetes in Black individuals may have genetic determinants in addition to adverse social factors. Further research may help understand the interplay between biological and social determinants of cardiometabolic health in Black individuals. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01206062.

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“…It is not immediately clear, for any biological variable, the extent to which biology is "inherent" or the result of external influences. What is clear is that social determinants play a large role in health outcomes influenced by biology, including blood pressure regulation [17,18]. In the context of areas such as epigenetics, within-life modification of the genome by a range of environmental influences, it is unclear what the term "inherent" even really means.…”

mentioning

confidence: 99%

Factors contributing to racial differences in neurogenic orthostatic hypotension

Charkoudian

Robinson

2021

Clin Auton Res

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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 (SPRINT)

Cited by 31 publications

References 43 publications

Relative impact of genetic ancestry and neighborhood socioeconomic status on all-cause mortality in self-identified African Americans

Relative impact of genetic ancestry and neighborhood socioeconomic status on all-cause mortality in self-identified African Americans

Genetic European Ancestry and Incident Diabetes in Black Individuals: Insights From the SPRINT Trial

Factors contributing to racial differences in neurogenic orthostatic hypotension

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