Unmasking Hormonal Mechanisms of Hypertension in Obesity
Notice bibliographique
Résumé
ABSTRACT Background Understanding hormonal mechanisms of obesity-related hypertension may inform the optimal approach to targeted therapy. Objectives To interrogate hormonal phenotypes of obesity-related hypertension. Methods 77 participants with obesity and hypertension underwent deep-phenotyping of adrenocortical hormones at baseline and following multiple dynamic maneuvers to suppress and stimulate hormone production, including: the seated saline suppression (SST), oral sodium loading (OSLT) test, dexamethasone suppression test (DST), and ACTH-stimulation (ACTHstim). Participants were classified into 3 aldosteronism phenotypes: (1) primary aldosteronism (PA) phenotype (low renin with non-suppressible aldosterone), low-renin phenotype (low renin and low aldosterone), and renin-dependent aldosteronism (high renin with renin-mediated aldosteronism). The DST was used to evaluate for ACTH-independent hypercortisolism and ACTHstim was used to evaluate ACTH-modulated adrenocortical hormone production. Results Participants were 55.4 ± 9.4 years, 66.2% women, and had a BMI of 34.8 ± 5.2 kg/m 2 . At baseline, 37.7% of participants had a PA phenotype. Following sodium loading with SST, a persistent PA phenotype was seen in 28.5% and unmasked in an additional 23.4% of participants (total 51.9%). Participants with an unmasked PA phenotype had renin-dependent aldosteronism prior to SST, and thus were not identified during baseline testing. Persistent renin-dependent aldosteronism following SST was identified in 23.4% of the cohort and was characterized by greater kaliuresis and higher aldosterone levels (at baseline and following dynamic maneuvers to modulate ACTH and angiotensin II). These patterns were all reproduced following sodium loading with the OSLT. The DST identified ACTH-independent hypercortisolism in 9.2% of participants. Conclusions Over 80% of participants with obesity-related hypertension reproducibly exhibited pathologic phenotypes of aldosteronism and/or hypercortisolism. These overlapping hormonal mechanisms reveal the multi-factorial nature of obesity-related hypertension and provide evidence to support aldosterone- and cortisol-directed therapies to treat hypertension in people with obesity. CONDENSED ABSTRACT Understanding hormonal mechanisms of obesity-related hypertension may inform targeted therapy. Participants with obesity and hypertension underwent deep-phenotyping procedures to detect the: primary aldosteronism (PA) phenotype, low-renin phenotype, renin-dependent aldosteronism phenotype, and ACTH-independent hypercortisolism. In total, 51.9% of participants had a PA phenotype, of which approximately half also had superimposed renin-dependent aldosteronism. Another 23.4% participants had just renin-dependent aldosteronism that was characterized by higher aldosterone levels and kaliuresis, and 9.2% of participants had hypercortisolism. Over 80% of individuals with obesity-related hypertension exhibited overlapping pathologic phenotypes of aldosteronism and/or hypercortisolism, providing mechanistic evidence to support the efficacy of aldosterone- and cortisol-directed therapy ( Central Illustration ).
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».