Metabolomics of hypertension in South Africans : the SABPA Study

Abstract

There has been growing concern in recent years about the alarmingly high prevalence and severity of hypertension and other cardiovascular diseases in individuals from newly (or recently) westernised countries such as South Africa. This is especially true for the Black ethnic group where higher average blood pressure values are seen, compared to their Caucasian counterparts. There is already an established connection between urbanisation and increased prevalence of lifestyle diseases in developed countries such as the USA. However, despite the global effort of clinicians and scientists investigating the aetiology of hypertension, regarding its involvement in cardio-metabolic disease no definitive biological mechanism has been elucidated, especially in the Black ethnic group of South Africa. This study thus aimed to investigate hypertension in Black and Caucasian South Africans in a holistic manner, utilising a metabolomics-based approach together with clinical data and targeted biochemical measured markers. Two metabolomics platforms were used to ensure wider metabolome coverage, namely gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). Study participants were divided into gender and ethnic groups and each group was further divided into quintiles according to average 24-hour ambulatory systolic blood pressure values. Only data from quintile 1 (normotensives) and quintile 5 (extreme hypertensives) were used in statistical analyses to ensure optimal separation between blood pressure groups. In the hypertensive Black males perturbations in several systems involved in ethanol metabolism were evident, being driven by a shifted global NADH/NAD+ ratio. Alterations in the bile acid metabolism of the hypertensive Black females were seen, while a more classical pre-diabetic insulin resistant state was observed in the hypertensive Caucasian females. In the hypertensive Caucasian males, disruptions in fatty acid metabolism and liver damage was evident, along with perturbations in detoxification systems. Obesity and perturbations in gut flora metabolism were evident in most of the hypertensive groups. Results from this study serve to demonstrate the power of applied metabolomics in the field of cardiovascular research, as novel metabolic pathways not previously associated with the pathogenesis of hypertension were found to be perturbed in hypertensives compared to their normotensive counterparts.