Unmasking Hormonal Mechanisms of Hypertension in Obesity

Figures

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  Figure 1. Plasma Renin Activity Before and After Saline Suppression Test Spaghetti plot representing individual participant’s plasma renin activity at baseline (light blue) and after the saline suppression test (dark blue). The dashed red line indicates the cutoff of 1 ng/mL/h. At baseline, 38 of 77 participants (49.4%) had plasma renin activity ≤1 ng/mL/h, while 39 of 77 (50.6%) had plasma renin activity >1 ng/mL/h. After the saline suppression test, 59 of 77 participants (76.6%) had a suppressed renin ≤1 ng/mL/h, while 18 of 77 (23.4%) remained nonsuppressed.

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  Figure 2. Aldosterone and Renin Phenotype at Baseline and After Saline Suppression Test (A) Scatterplots of plasma aldosterone and plasma renin activity at baseline, trajectories from baseline to postsaline suppression test, and postsaline suppression, showing 3 phenotypes: 1) primary aldosteronism phenotype in red (plasma renin activity [PRA] ≤1 ng/mL/h with plasma aldosterone concentration [PAC] ≥10 ng/dL at baseline or ≥7.8 ng/dL post-SST); 2) renin-dependent aldosteronism phenotype in dark blue (PRA >1 ng/mL/h); and 3) low-renin phenotype in light blue (PRA ≤1 with PAC <7.8 ng/dL). (B) Sankey diagram illustrating phenotype trajectories from baseline to postsaline loading, highlighting persistent (28.5%) and unmasked (23.4%) forms of primary aldosteronism phenotype and persistent renin-dependent aldosteronism (23.4%) phenotype.

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  Figure 3. Performance of 2025 Endocrine Society Guidelines in Identifying PA Phenotype In Participants With Obesity and Hypertension (A) Patients with positive saline suppression test (PRA ≤1 ng/mL/h and PAC ≥7.8 ng/dL) were identified as having PA phenotype. Among these, only 42.5% would have screened positive at baseline by 2025 Endocrine Society criteria, while the remaining 57.5% failed baseline screening caused by nonsuppressed renin, low aldosterone-to-renin ratio, or both. (B) Using the stricter postsaline suppression test aldosterone cutoff (≥10 ng/dL), 41.4% would have screened positive at baseline, leaving 58.6% missed by Endocrine Society screening, predominantly caused by combined nonsuppressed renin and low aldosterone-to-renin ratio. Abbreviations as in Figure 2.

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  Figure 4. Aldosterone and Cortisol Responses to Dexamethasone Suppression and ACTH Stimulation Test Across Phenotypes (A) Postdexamethasone suppression test: Aldosterone (light gray bars) but not cortisol (dark gray bars) differed significantly across phenotypes (P = 0.001 for aldosterone; P = 0.659 for cortisol), with renin-dependent phenotype yielding the highest ACTH-independent aldosterone values. (B) Post-ACTH stimulation test: aldosterone showed significant differences across phenotypes (P < 0.001), while cortisol responses were similar (P = 0.451). Again, with renin-dependent phenotype yielding highest ACTH-dependent aldosterone values. Data are presented as median (Q1-Q3) and compared using the Kruskal-Wallis test with Dunn’s post hoc test. Overall P values (Kruskal-Wallis test) are shown above the figures; pairwise comparisons (Dunn’s post hoc test) are indicated by symbols within the figure. ∗P < 0.05, ∗∗P < 0.01, and ∗∗∗P < 0.001.