An exploratory analysis of comparative plasma metabolomic and lipidomic profiling in salt-sensitive and salt-resistant individuals from The Dietary Approaches to Stop Hypertension Sodium Trial

Parul Chaudhary, Elena Velkoska, Richard D Wainford, Parul Chaudhary, Elena Velkoska, Richard D Wainford

Abstract

Objective: This study conducted exploratory metabolomic and lipidomic profiling of plasma samples from the DASH (Dietary Approaches to Stop Hypertension) Sodium Trial to identify unique plasma biomarkers to identify salt-sensitive versus salt-resistant participants.

Methods: Utilizing plasma samples from the DASH-Sodium Trial, we conducted untargeted metabolomic and lipidomic profiling on plasma from salt-sensitive and salt-resistant DASH-Sodium Trial participants. Study 1 analyzed plasma from 106 salt-sensitive and 85 salt-resistant participants obtained during screening when participants consumed their regular diet. Study 2 examined paired within-participant plasma samples in 20 salt-sensitive and 20 salt-resistant participants during a high-salt and low-salt dietary intervention. To investigate differences in metabolites or lipidomes that could discriminate between salt-sensitive and salt-resistant participants or the response to a dietary sodium intervention Principal Component Analysis and Orthogonal Partial Least Square Discriminant Analysis was conducted. Differential expression analysis was performed to validate observed variance and to determine the statistical significance.

Results: Differential expression analysis between salt-sensitive and salt-resistant participants at screening revealed no difference in plasma metabolites or lipidomes. In contrast, three annotated plasma metabolites, tocopherol alpha, 2-ketoisocaproic acid, and citramalic acid, differed significantly between high-sodium and low-sodium dietary interventions in salt-sensitive participants.

Conclusion: In DASH-Sodium Trial participants on a regular diet, plasma metabolomic or lipidomic signatures were not different between salt-sensitive and salt-resistant participants. High-sodium intake was associated with changes in specific circulating metabolites in salt-sensitive participants. Further studies are needed to validate the identified metabolites as potential biomarkers that are associated with the salt sensitivity of blood pressure.

Trial registration: ClinicalTrials.gov NCT00000608.

Conflict of interest statement

There are no conflicts of interest.

Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.

Figures

FIGURE 1
FIGURE 1
Orthogonal Partial Least Square Discriminant Analysis score plot of baseline plasma metabolites for salt-sensitive (SS) (n = 106) and salt-resistant (SR) (n = 85) participants from Dietary Approaches to Stop Hypertension–Sodium Trial. Plots were created from a partial least squares discriminant analysis of 191 fasted plasma samples collected at the time of screening from participants maintained on their regular diet (i.e. prior to a dietary intervention).
FIGURE 2
FIGURE 2
Dot plot showing the −log10 of the adjusted P value for all baseline plasma metabolites grouped by superclass for analysis comparing salt-sensitive (SS) (n = 106) and salt-resistant (SR) (n = 85) participants. The analysis was conducted in the plasma samples collected at the time of screening from Dietary Approaches to Stop Hypertension–sodium trial participants maintained on their regular diet (i.e. prior to a dietary intervention). Only annotated metabolites (KEGG IDs, metabolite names) are shown.
FIGURE 3
FIGURE 3
Dot plot showing the −log10 of the adjusted P value for all plasma metabolites grouped by superclass for analysis comparing high-salt dietary intervention relative to low-salt dietary intervention from the salt-sensitive (SS) (n = 20) Dietary Approaches to Stop Hypertension–sodium trial participants maintained on a control diet. Only annotated metabolites (KEGG IDs, metabolite names) are shown.
FIGURE 4
FIGURE 4
Orthogonal Partial Least Square Discriminant Analysis score plot of baseline plasma lipid profile for salt-sensitive (SS) (n = 106) and salt-resistant (SR) (n = 85) individuals from Dietary Approaches to Stop Hypertension–sodium trial participants. Plots were created from a partial least squares discriminant analysis of 191 fasted plasma samples collected at the time of screening from participants maintained on their regular diet (i.e. prior to a dietary intervention).

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