{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T05:44:33Z","timestamp":1776231873565,"version":"3.50.1"},"reference-count":160,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Primary aldosteronism (PA) is associated with a substantially higher cardiovascular risk than essential hypertension, a disparity that cannot be fully explained by blood pressure elevation alone. Clinical studies consistently demonstrate that cardiovascular morbidity and mortality often persist in patients with PA despite adequate blood pressure control and standard therapy, underscoring the existence of residual cardiovascular risk. Accumulating experimental and clinical evidence identifies inflammation as a central mediator of aldosterone-induced cardiovascular injury. Excess aldosterone drives immune\u2013inflammatory remodeling through coordinated activation of innate and adaptive immune responses, including macrophage- and T cell\u2013dependent pathways, as well as downstream signaling cascades such as inflammasome activation and interleukin-6\u2013related trans-signaling. These processes promote myocardial fibrosis, vascular dysfunction, and adverse cardiac remodeling, providing a mechanistic basis for the heightened cardiovascular risk observed in PA. Although mineralocorticoid receptor (MR) antagonists remain the cornerstone of medical therapy for PA, MR blockade alone may be insufficient to fully suppress aldosterone-driven inflammatory and non-hemodynamic effects. Persistent activation of these pathways offers a plausible explanation for the residual cardiovascular risk observed in treated patients. Emerging therapeutic strategies aim to overcome these limitations through combination approaches. Aldosterone synthase inhibitors (ASIs), by targeting aldosterone production upstream, may complement MR antagonism, while interventions directed at inflammatory pathways and non-genomic aldosterone signaling could further enhance cardiovascular protection. This review integrates current mechanistic and clinical evidence on inflammatory drivers and residual risk in PA and discusses emerging combination strategies to optimize cardiovascular risk reduction in this high-risk population.<\/jats:p>","DOI":"10.3389\/fendo.2026.1802307","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T04:45:35Z","timestamp":1776228335000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cardiovascular risk in primary aldosteronism: inflammatory drivers, residual risk, and emerging combination strategies"],"prefix":"10.3389","volume":"17","author":[{"given":"Haoze","family":"Liu","sequence":"first","affiliation":[{"name":"Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences Tongji Shanxi Hospital","place":["Taiyuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zejun","family":"Wu","sequence":"additional","affiliation":[{"name":"Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences Tongji Shanxi Hospital","place":["Taiyuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinzhe","family":"Liu","sequence":"additional","affiliation":[{"name":"Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences Tongji Shanxi Hospital","place":["Taiyuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuyuan","family":"Hu","sequence":"additional","affiliation":[{"name":"Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences Tongji Shanxi Hospital","place":["Taiyuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaixuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology, Peking University People\u2019s Hospital","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiwen","family":"Shang","sequence":"additional","affiliation":[{"name":"Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences Tongji Shanxi Hospital","place":["Taiyuan, China"]},{"name":"Department of Urology, Shanxi Bethune Hospital, Shanxi Academy of Medical Science, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University","place":["Taiyuan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecl.2015.02.001","article-title":"Development of adrenal cortex zonation","volume":"44","author":"Xing","year":"2015","journal-title":"Endocrinol Metab Clinics North America"},{"key":"B2","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.jsbmb.2015.05.008","article-title":"Aldosterone biosynthesis in the human adrenal cortex and associated disorders","volume":"153","author":"Nakamura","year":"2015","journal-title":"J Steroid Biochem Mol Biol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c130037","article-title":"Regulation of aldosterone synthesis and secretion","volume":"4","author":"Bollag","year":"2014","journal-title":"Compr Physiol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1152\/advan.00051.2001","article-title":"Aldosterone","volume":"26","author":"Booth","year":"2002","journal-title":"Adv Physiol Educ"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2011.07.034","article-title":"Acute and chronic regulation of aldosterone production","volume":"350","author":"Hattangady","year":"2012","journal-title":"Mol Cell Endocrinol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2016.00072","article-title":"Role of ACTH and other hormones in the regulation of aldosterone production in primary aldosteronism","volume":"7","author":"El Ghorayeb","year":"2016","journal-title":"Front Endocrinol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1007\/s10741-005-2343-3","article-title":"Aldosterone biosynthesis, regulation, and classical mechanism of action","volume":"10","author":"Williams","year":"2005","journal-title":"Heart Fail. 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