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)

This post hoc analysis of data from the Systolic Blood Pressure Intervention Trial determines the association between the proportion of West African ancestry with response to antihypertensive medication, blood pressure control, kidney function, and risk of adverse cardiovascular events among self-identified Black individuals. Importance Self-identified Black race is associated with higher hypertension prevalence and worse blood pressure (BP) control compared with other race/ethnic groups. The contribution of genetic West African ancestry to these racial disparities appears not to have been completely determined. Objective To determine the association between the proportion of West African ancestry with the response to antihypertensive medication, BP control, kidney function, and risk of adverse cardiovascular (CV) events among self-identified Black individuals in the Systolic Blood Pressure Intervention Trial (SPRINT). Design, Setting, and Participants This post hoc analysis of the SPRINT trial incorporated data from a multicenter study of self-identified Black participants with available West African ancestry proportion, estimated using 106 biallelic autosomal ancestry informative genetic markers. Recruitment started on October 20, 2010, and ended on August 20, 2015. Data were analyzed from May 2020 to September 2020. Main Outcomes and Measures Trajectories of BP and kidney function parameters on follow-up of the trial were assessed across tertiles of the proportion of West African ancestry using linear mixed-effect modeling after adjustment for potential confounders. Multivariable adjusted Cox models evaluated the association of West African ancestry with the risk of composite CV events (nonfatal myocardial infarction, CV death, and heart failure event). Results Among 2466 participants in the current analysis (1122 women [45.5%]; median West African ancestry, 81% [interquartile range, 73%-87%]), there were 120 composite CV events (4.9%) over a mean (SD) of 3.2 (0.9) years of follow-up. At baseline, mean (SD) high-density lipoprotein cholesterol levels were higher (tertile 3: 56.5 [15.0] mg/dL vs tertile 1: 54.2 [14.9] mg/dL; P = .006), smoking prevalence (never smoking: tertile 3: 367 [47.9%] vs tertile 1: 372 [42.2%]; P = .009) and mean (SD) Framingham Risk scores (tertile 3: 16.7 [9.7] vs tertile 1: 18.1 [10.2]; P = .01) were lower, and baseline BP was not different across increasing tertiles of West African ancestry. On follow-up, there was no evidence of differences in longitudinal trajectories of BP, kidney function parameters, or left ventricular mass (Cornell voltage by electrocardiogram) across tertiles of West African ancestry in either intensive or standard treatment arms. In adjusted Cox models, higher West African ancestry was associated with a lower risk of a composite CV event after adjustment for potential confounders (adjusted hazard ratio per 5% higher West African ancestry, 0.92 [95% CI, 0.85-0.99]). Conclusions and Relevance Among self-reported Black individuals enrolled in SPRINT, the trajectories of BP, kidney function, and left ventricular mass over time were not different across tertiles of the proportion of West African ancestry. A higher proportion of West African ancestry was associated with a modestly lower risk for CV events. These findings suggest that extrinsic and structural societal factors, more than genetic ancestry, may be the major drivers of the well-established racial disparity in cardiovascular health associated with hypertension. Question Among SPRINT participants self-identified as Black, what are the associations of global genetic West African ancestry with response to antihypertensive medication, blood pressure control, and cardiovascular outcomes? Findings Global West African ancestry proportion was not significantly associated with response to antihypertensive medication, blood pressure control, or kidney function changes over time. A higher proportion of West African ancestry was associated with a modestly lower risk for cardiovascular events. Meaning These findings highlight the greater importance of nonbiological risk factors-including socioeconomic status, environmental factors, educational attainment, behavioral characteristics, structural racism, and access to health care-in existing disparities in hypertension control and downstream adverse cardiovascular risk.

Automated summary

The study found that among self-identified Black individuals in the SPRINT trial, trajectories of blood pressure, kidney function, and left ventricular mass over time did not differ across tertiles of West African ancestry proportion. A higher proportion of West African ancestry was associated with a slightly lower risk for cardiovascular events. These results suggest that nonbiological factors may play a larger role than genetic ancestry in contributing to existing disparities in hypertension control and cardiovascular risk.