An Overview of Metabolic Phenotyping in Blood Pressure Research

Abstract

Purpose of the ReviewThis review presents the analytical techniques, processing and analytical steps used in metabolomics phenotyping studies, as well as the main results from epidemiological studies on the associations between metabolites and high blood pressure.Recent FindingsA variety of metabolomic approaches have been applied to a range of epidemiological studies to uncover the pathophysiology of high blood pressure. Several pathways have been suggested in relation to blood pressure including the possible role of the gut microflora, inflammatory, oxidative stress, and lipid pathways. Metabolic changes have also been identified associated with blood pressure lowering effects of diets high in fruits and vegetables and low in meat intake. However, the current body of literature on metabolic profiling and blood pressure is still in its infancy, not fully consistent and requires careful interpretation.SummaryMetabolic phenotyping is a promising approach to uncover metabolic pathways associated with high blood pressure and throw light into the complex pathophysiology of hypertension.

Sexual Dimorphism of Metabolomic Profile in Arterial Hypertension

“…Several metabolomic studies have demonstrated the existence of biological signatures in the blood and urine of patients with high blood pressure from various regions, including African populations, and using various analytical platforms and study designs. These studies have been recently reviewed 9,10 . The metabolomic signatures published to date showed a wide variety of quantitative metabolite traits related to arterial hypertension such as amino acids (alanine, serine, glycine, methionine, arginine, tyrosine and isoleucine), nucleotide bases (adenine and uracil), hormones (epiandrosterone sulfate, 5 α-androstan-3β-diol disulfate, androsterone sulfate, melatonin, cortolone, dihydroxyphenylglycol, and hydroxyandrosterone), organic acids (hippurate, pyruvate, hexadecanedioate, formate, methyl nicotinate, dicarboxylic acids, butyrate and fumarate, lactate, malate and pyruvate), and hexoses [11][12][13][14][15][16][17] .…”

Global Plasma Metabolomics to Identify Potential Biomarkers of Blood Pressure Progression

“…In this study, we investigated associations of a large number of circulating metabolites with longitudinal BP progression in a population-based cohort. Accounting for multiple testing, and in mixed models with multivariable adjustment, baseline levels of 4 metabolites (ceramide [d18:1, C24:0], triacylglycerol [C16:0, C16:1], total glycerolipids, and oleic acid [C18:cis [9]1]) were positively associated with longitudinal change in DBP. One metabolite (cholesterylester C16:0) was negatively associated with DBP change.…”

“…In the validation phase, 11 metabolites available in the validation cohort that had similar structure to the 5 top findings in the discovery cohort were investigated. Diacylglycerol ( In secondary analyses in the discovery cohort, cubic spline models demonstrated chiefly linear association of metabolites on diastolic BP among ceramide (d18:1, C24:0), triacylglycerol (C16:0, C16:1), glycerolipids, and cholesterylester (C16:0), except oleic acid (C18:cis [9]1; Figure III in the Data Supplement). In sensitivity analyses, the heterogeneity between participants with or without antihypertensive treatment during follow-up was low (I square=0, Figure IX in the Data Supplement).…”

“…8 Previous human studies using metabolomics approaches to explore the pathophysiology of hypertension have suggested several potential pathways, including inflammatory processes, oxidative stress, lipid profile, and gut microflora. 9,10 But previous studies in the field are scarce, [11][12][13][14] findings are inconsistent, and most studies are limited by small sample sizes and crosssectional study designs. Only one longitudinal study has reported on associations of lipid metabolites with risk of incident hypertension.…”

Metabolomic Signature of Early Vascular Aging (EVA) in Hypertension

“…Metabolomics is a high-throughput mass spectrometry method that offers a powerful platform tools to explore metabolic alterations associated with pathophysiological states. Several studies have indeed proven that metabolomics provide important insight into cardiovascular disease pathogenesis such as cardiac hypertrophy, heart failure, coronary heart disease, cardiometabolic disease, and hypertension as well as identify new potential cardiovascular disease biomarkers (Nikolic et al, 2014;Tzoulaki et al, 2018). Metabolomic profiling is also thought to integrate valuable information reflecting genomic, epigenetic, and transcriptomic variation with the effect of environmental exposures such as diet, physical activity which is unique for each individual (McGarrah et al, 2018;Leon-Mimila et al, 2019).…”