Searching for Metabolic Markers for Hypertension in Human Urine

Figures

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  Figure 1. Summary of changes in metabolite levels observed between the NT group and the HTo (left) and HTall (right) groups. The symbols indicate an increase (▲) or decrease (▼) in urinary metabolite levels in the HTo or HTall vs. the NT group; the number between parenthesis indicates the p-value. In the circles of each group/subgroup, we indicated in parenthesis the number (n) of participants in each group/subgroup. Statistical analysis was performed using Student’s t-test or Mann–Whitney test.

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  Figure 2. Violin plots representing the distribution of metabolite concentrations (mmol/L) for the metabolites that were significantly different between the NT group vs. the HTo subgroup. (A) acetone; (B) citrate; (C) 4-hydroxyphenylacetate; (D) methylglutaconate; (E) N-isovaleroylglycine; (F) oxaloacetate; (G) phenylalanine; (H) pyridoxate; (I) sarcosine. Each dot represents each participant’s urine sample. The width of the violin plot indicates the density of the data at each concentration. Statistical analysis was performed using Student t-test (STT). * p < 0.05, *** p < 0.001 vs. NT group.

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  Figure 3. Comparison of urinary metabolite levels between the HTo subgroup and subgroups of hypertensive individuals with dyslipidemia (with or without other comorbidities): hypertensive individuals with dyslipidemia only (HTdl), hypertensive individuals with dyslipidemia and diabetes (HTdb•dl) and hypertensive individuals with dyslipidemia and one cardiac disease (HTcd•dl). Comparison was performed between two subgroups at a time using Kruskal–Wallis test (KWT), followed by post hoc Dunn–Bonferroni Test. The table indicates all the metabolites that had a significant KWT test result (p < 0.05) and indicates if there was an increase (▲) or decrease (▼) in each metabolite and the percentage of change relative to the first mentioned subgroup. * p < 0.05; ** p < 0.01.

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  Figure 4. Comparison of urinary metabolite levels between the HTo subgroup and subgroups of hypertensive individuals with diabetes (with or without other comorbidities): hypertensive individuals with diabetes only (HTdb), hypertensive participants with diabetes and dyslipidemia (HTdb•dl), and hypertensive participants with diabetes and one cardiac disease (HTcd•db). Comparison was performed between two subgroups at a time using Kruskal–Wallis test (KWT), followed by post hoc Dunn–Bonferroni test. The table indicates all the metabolites that had a significant KWT test result (p < 0.05) and if there was an increase (▲) or decrease (▼) in each metabolite and the percentage of change relative to the first mentioned subgroup. * p < 0.05; ** p < 0.01.

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  Figure 5. Comparison of urinary metabolite levels between the HTo subgroup and subgroups of hypertensive individuals with one cardiac disease (with or without other comorbidities): hypertensive individuals with one cardiac disease only (HTcd), hypertensive individuals with one cardiac disease and dyslipidemia disease (HTcd•dl) and hypertensive individuals with one cardiac disease and diabetes (HTcd•db). Comparison was performed between two subgroups at a time using Kruskal–Wallis test (KWT), followed by post hoc Dunn–Bonferroni test. The table indicates all the metabolites that had a significant KWT test result (p < 0.05) and if there was an increase (▲) or decrease (▼) in each metabolite and the percentage of change relative to the first mentioned subgroup. * p < 0.05; ** p < 0.01. N/A: percentage of change not applicable (baseline value = 0).

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  Figure 6. AUROC analysis to discriminate HTo (A) and HTall (B) from NT based on the urinary concentrations of the following metabolites: acetone (Ace), citrate (Cit), 4-hydroxyphenylacetate (4-HPAA), 3-methylglutaconate (MG), N-isovaleroylglycine (N-IVG), oxaloacetate (Oxa), phenylalanine (Phe), pyridoxate (Pyr), and sarcosine (Sar).

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  Figure 7. NMR analysis flowchart for human urine metabolomic studies.