Use of metabolomics to elucidate the metabolic perturbation associated with hypertension in a black South African male cohort: the SABPA study

Abstract

There is concern about the increasing burden of essential hypertension in urban–dwelling black South Africans, especially males. Several studies have investigated urbanization and hypertension in South Africans, but in–depth metabolomics studies on these urbanized hypertensives are still lacking. We aimed to investigate hypertension via two metabolomics methods in order to explore underlying biological mechanisms, demonstrating the effectiveness of these methods in cardiovascular research. A comprehensive characterization of a group (n = 25) of black male South Africans was performed using urinary gas chromatography–mass spectrometry and liquid chromatography–mass spectrometry metabolic profiling in conjunction with 24–hour ambulatory blood pressure readings and anthropometric, clinical, and biochemical markers. Average 24–hour blood pressure readings served as the grouping variable, and test subjects were divided into quintiles. Statistical analyses were performed on Quintile 1 (normotensive subjects) and Quintile 5 (extreme hypertensive subjects). After feature selection was performed, several metabolites and cardiometabolic risk markers, including abdominal obesity and markers of liver damage, inflammation, and oxidative stress were significantly perturbed in Quintile 5 (hypertensives) compared with Quintile 1 (P < .05). Pathway analysis revealed perturbations in several systems involved in ethanol metabolism via shifted global NADH/NAD$^+$ ratio. Although alcohol abuse has been established as a risk factor for hypertension, this study illustrated a metabolic perturbation associated with alcohol abuse, contributing to the development of hypertension—possibly by altering bioenergetics through a shift in the NADH/NAD$^+$ ratio. Following this finding, future intervention studies on alcohol moderation, as well as further enhancement of metabolomics methods in cardiovascular research are highly recommended.