Abstract
Introduction: In the United States, the risk of stroke is greater among Black compared to White adults. Furthermore, hypertension has a greater impact on stroke risk among Black adults. We hypothesized that race-specific metabolites may account for some of this observed disparity. Methods: This was a case-cohort study nested in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. Incident ischemic stroke cases (n=1,075) were compared with a random cohort sample (n=968). Metabolites were measured by liquid chromatography-tandem mass spectrometry. Weighted logistic regression and Cox proportional hazard model were used to identify race-specific metabolites in association with prevalent hypertension and incident stroke respectively. Candidate metabolites were assessed for mediation between hypertension and incident ischemic stroke. Linear regression was used to explore the association of metabolites with lifestyle factors. Results: A total of 162 plasma metabolites were quantified. Of these, gluconic acid was associated with prevalent hypertension in Black adults (OR=1.86, 95% CI=1.39-2.47, P =2.58x10 -5 ) but not in White adults (OR=1.00, 95% CI=0.80-1.24, P =0.97; P for interaction=4.57x10 -4 ). Gluconic acid was also associated with incident ischemic stroke among Black adults (HR=1.53, 95% CI=1.28-1.81, P =1.76x10 -6 ) but not White adults (HR=1.16, 95% CI=1.00-1.34, P =0.057; P for interaction=0.019). Gluconic acid mediated 25.4% (95% CI=4.1%-46.8%, P =0.02) of the association between hypertension and ischemic stroke among Black adults. Specific lifestyle factors were linked to elevated gluconic acid level among Black adults in multivariable analysis, including a Southern diet (β=0.18, 95% CI=0.08-0.28, P <0.001), lower educational attainment (β=0.45, 95% CI=0.19-0.72, P =0.001), and lack of exercise (β=0.26, 95% CI=0.01-0.51, P =0.045). Conclusions: Gluconic acid is a lifestyle-related biomarker that is associated with prevalent hypertension, incident ischemic stroke, and mediates the relationship between hypertension and ischemic stroke in Black adults. Key factors linked to gluconic acid include Southern diet, low educational attainment, and low physical activity.
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