Academic Journal
Data-driven cluster analysis and external validation identify phenotypic subgroups in renin-independent aldosteronism with differential cardiovascular risk and therapeutic implications.
| Title: | Data-driven cluster analysis and external validation identify phenotypic subgroups in renin-independent aldosteronism with differential cardiovascular risk and therapeutic implications. |
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| Authors: | Liu, Yuqing, Zhang, Zhiheng, Zhou, Haifeng, Yan, Yutong, Zhou, Mei, Wang, Cong, Gao, Maoting, Tao, Jun, Bao, Meiling, Yang, Tao, Sun, Min, Yang, Yuhong |
| Source: | Frontiers in Endocrinology; 12/29/2025, p1-16, 16p |
| Subject Terms: | Cardiovascular diseases risk factors, Phenotypes, Cluster analysis (Statistics), Medical protocols, Mineralocorticoid receptors, Metabolic disorders, Renin-angiotensin system |
| Abstract: | Background: Renin-independent aldosterone secretion contributes to aldosteronism and heightened cardiovascular risk, but renin-independent aldosteronism is highly heterogenous. A refined classification may assist in identifying individuals with distinct cardiovascular risk profiles and guide individualized treatment strategies. Methods: Unsupervised hierarchical clustering was performed using 12 clinical parameters from patients with renin-independent aldosteronism in our registry cohort (n=404). The cluster centroids derived from the discovery cohort were fixed and applied to the Framingham Heart Study Third Generation cohort (n=417) for subject classification. The identified clusters were evaluated for their association with cardiovascular outcomes, assessed by echocardiographic parameters, serum biomarkers and cardiovascular event rates. Results: Three replicable clusters of patients with renin-independent aldosteronism were identified. Patients in cluster 2 showed the most severe metabolic abnormalities with the highest lipid and glucose levels, while patients in cluster 3 displayed the highest aldosterone levels. Both clusters 2 and 3 showed elevated baseline blood pressure and left ventricular remodeling compared with cluster 1. Cluster 2 exhibited the highest risk of cardiovascular disease, chronic heart failure and atrial fibrillation, followed by cluster 3, which showed a higher incidence of cardiovascular disease compared with cluster 1. Conclusions: We identified 3 subgroups with differing degrees of target organ damage and cardiovascular risk. Our findings establish metabolic dysfunction, rather than aldosterone excess, as a potential dominant cardiovascular risk driver in RIA patients, defining a new risk paradigm. Patients with renin-independent aldosteronism with metabolic dysfunction or high aldosterone levels may benefit from mineralocorticoid receptor antagonists with different priorities for metabolic and cardiovascular protection. This new refined classification may help tailor optimal treatment strategies for patients with heterogenous renin-independent aldosteronism. [ABSTRACT FROM AUTHOR] |
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| Database: | Complementary Index |
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| Items | – Name: Title Label: Title Group: Ti Data: Data-driven cluster analysis and external validation identify phenotypic subgroups in renin-independent aldosteronism with differential cardiovascular risk and therapeutic implications. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Liu%2C+Yuqing%22">Liu, Yuqing</searchLink><br /><searchLink fieldCode="AR" term="%22Zhang%2C+Zhiheng%22">Zhang, Zhiheng</searchLink><br /><searchLink fieldCode="AR" term="%22Zhou%2C+Haifeng%22">Zhou, Haifeng</searchLink><br /><searchLink fieldCode="AR" term="%22Yan%2C+Yutong%22">Yan, Yutong</searchLink><br /><searchLink fieldCode="AR" term="%22Zhou%2C+Mei%22">Zhou, Mei</searchLink><br /><searchLink fieldCode="AR" term="%22Wang%2C+Cong%22">Wang, Cong</searchLink><br /><searchLink fieldCode="AR" term="%22Gao%2C+Maoting%22">Gao, Maoting</searchLink><br /><searchLink fieldCode="AR" term="%22Tao%2C+Jun%22">Tao, Jun</searchLink><br /><searchLink fieldCode="AR" term="%22Bao%2C+Meiling%22">Bao, Meiling</searchLink><br /><searchLink fieldCode="AR" term="%22Yang%2C+Tao%22">Yang, Tao</searchLink><br /><searchLink fieldCode="AR" term="%22Sun%2C+Min%22">Sun, Min</searchLink><br /><searchLink fieldCode="AR" term="%22Yang%2C+Yuhong%22">Yang, Yuhong</searchLink> – Name: TitleSource Label: Source Group: Src Data: Frontiers in Endocrinology; 12/29/2025, p1-16, 16p – Name: Subject Label: Subject Terms Group: Su Data: <searchLink fieldCode="DE" term="%22Cardiovascular+diseases+risk+factors%22">Cardiovascular diseases risk factors</searchLink><br /><searchLink fieldCode="DE" term="%22Phenotypes%22">Phenotypes</searchLink><br /><searchLink fieldCode="DE" term="%22Cluster+analysis+%28Statistics%29%22">Cluster analysis (Statistics)</searchLink><br /><searchLink fieldCode="DE" term="%22Medical+protocols%22">Medical protocols</searchLink><br /><searchLink fieldCode="DE" term="%22Mineralocorticoid+receptors%22">Mineralocorticoid receptors</searchLink><br /><searchLink fieldCode="DE" term="%22Metabolic+disorders%22">Metabolic disorders</searchLink><br /><searchLink fieldCode="DE" term="%22Renin-angiotensin+system%22">Renin-angiotensin system</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Background: Renin-independent aldosterone secretion contributes to aldosteronism and heightened cardiovascular risk, but renin-independent aldosteronism is highly heterogenous. A refined classification may assist in identifying individuals with distinct cardiovascular risk profiles and guide individualized treatment strategies. Methods: Unsupervised hierarchical clustering was performed using 12 clinical parameters from patients with renin-independent aldosteronism in our registry cohort (n=404). The cluster centroids derived from the discovery cohort were fixed and applied to the Framingham Heart Study Third Generation cohort (n=417) for subject classification. The identified clusters were evaluated for their association with cardiovascular outcomes, assessed by echocardiographic parameters, serum biomarkers and cardiovascular event rates. Results: Three replicable clusters of patients with renin-independent aldosteronism were identified. Patients in cluster 2 showed the most severe metabolic abnormalities with the highest lipid and glucose levels, while patients in cluster 3 displayed the highest aldosterone levels. Both clusters 2 and 3 showed elevated baseline blood pressure and left ventricular remodeling compared with cluster 1. Cluster 2 exhibited the highest risk of cardiovascular disease, chronic heart failure and atrial fibrillation, followed by cluster 3, which showed a higher incidence of cardiovascular disease compared with cluster 1. Conclusions: We identified 3 subgroups with differing degrees of target organ damage and cardiovascular risk. Our findings establish metabolic dysfunction, rather than aldosterone excess, as a potential dominant cardiovascular risk driver in RIA patients, defining a new risk paradigm. Patients with renin-independent aldosteronism with metabolic dysfunction or high aldosterone levels may benefit from mineralocorticoid receptor antagonists with different priorities for metabolic and cardiovascular protection. This new refined classification may help tailor optimal treatment strategies for patients with heterogenous renin-independent aldosteronism. [ABSTRACT FROM AUTHOR] – Name: Abstract Label: Group: Ab Data: <i>Copyright of Frontiers in Endocrinology is the property of Frontiers Media S.A. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.3389/fendo.2025.1686480 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 16 StartPage: 1 Subjects: – SubjectFull: Cardiovascular diseases risk factors Type: general – SubjectFull: Phenotypes Type: general – SubjectFull: Cluster analysis (Statistics) Type: general – SubjectFull: Medical protocols Type: general – SubjectFull: Mineralocorticoid receptors Type: general – SubjectFull: Metabolic disorders Type: general – SubjectFull: Renin-angiotensin system Type: general Titles: – TitleFull: Data-driven cluster analysis and external validation identify phenotypic subgroups in renin-independent aldosteronism with differential cardiovascular risk and therapeutic implications. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Liu, Yuqing – PersonEntity: Name: NameFull: Zhang, Zhiheng – PersonEntity: Name: NameFull: Zhou, Haifeng – PersonEntity: Name: NameFull: Yan, Yutong – PersonEntity: Name: NameFull: Zhou, Mei – PersonEntity: Name: NameFull: Wang, Cong – PersonEntity: Name: NameFull: Gao, Maoting – PersonEntity: Name: NameFull: Tao, Jun – PersonEntity: Name: NameFull: Bao, Meiling – PersonEntity: Name: NameFull: Yang, Tao – PersonEntity: Name: NameFull: Sun, Min – PersonEntity: Name: NameFull: Yang, Yuhong IsPartOfRelationships: – BibEntity: Dates: – D: 29 M: 12 Text: 12/29/2025 Type: published Y: 2025 Identifiers: – Type: issn-print Value: 16642392 Titles: – TitleFull: Frontiers in Endocrinology Type: main |
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