{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T22:09:08Z","timestamp":1783116548903,"version":"3.54.6"},"reference-count":17,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,7,14]],"date-time":"2020-07-14T00:00:00Z","timestamp":1594684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,7,14]],"date-time":"2020-07-14T00:00:00Z","timestamp":1594684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL136567"],"award-info":[{"award-number":["R01HL136567"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR002541"],"award-info":[{"award-number":["UL1TR002541"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Endocr Disord"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Statins are the first-line pharmaceutical agent in the management of hypercholesterolemia and cardiovascular (CV) risk reduction, and the most commonly prescribed class of drugs worldwide. Studies describing CV risk reduction independent of LDL-cholesterol lowering have evoked an interest in the pleiotropic mechanisms of statins\u2019 benefits. We recently demonstrated that administration of statins in animal models lowers aldosterone levels and observed an association between statin use and reduced aldosterone levels in two human cohorts, with lipophilic statins displaying a greater effect than hydrophilic statins. Therefore, we designed a randomized, placebo-controlled, double-blinded intervention study to assess whether statin treatment lowers aldosterone in a type-dependent manner in humans, with simvastatin (lipophilic) showing a greater effect than pravastatin (hydrophilic).<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods\/design<\/jats:title>\n<jats:p>One hundred five healthy participants will be recruited from the general population to enroll in a 12-week, randomized, placebo-controlled, double-blinded, 3-arm clinical trial. Ninety participants are anticipated to complete the protocol. After baseline assessment of aldosterone levels, participants will be randomized to daily simvastatin, pravastatin, or placebo. Aldosterone levels will be assessed after 2\u2009days on study drug and again after 6\u2009weeks and 12\u2009weeks on study drug. Prior to each aldosterone assessment, participants will consume an isocaloric sodium and potassium-controlled run-in diet for 5\u2009days. Assessments will occur on an inpatient research unit to control for diurnal, fasting, and posture conditions. The primary outcome will compare 12-week angiotensin II-stimulated serum aldosterone by study drug. Secondary outcomes will compare baseline and 12-week 24-h urine aldosterone by study drug.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Discussion<\/jats:title>\n<jats:p>Results from this rigorous study design should provide strong support that statins lower aldosterone levels in humans. These results may explain some of the beneficial effects of statins that are not attributed to the LDL-lowering effect of this important class of medications. Results would demonstrate that statin lipophilicity is an important attribute in lowering aldosterone levels. The outcomes of this program will have implications for the design of studies involving statin medications, as well as for the differential use of classes of statins.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Trial registration<\/jats:title>\n<jats:p>ClinicalTrials.gov; <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02871687\">NCT02871687<\/jats:ext-link>; First Posted August 18, 2016.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12902-020-00587-4","type":"journal-article","created":{"date-parts":[[2020,7,14]],"date-time":"2020-07-14T14:06:56Z","timestamp":1594735616000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A clinical trial to evaluate the effect of statin use on lowering aldosterone levels"],"prefix":"10.1186","volume":"20","author":[{"given":"Ezra S.","family":"Hornik","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne E.","family":"Altman-Merino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew W.","family":"Koefoed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayla M.","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella B.","family":"Stone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica A.","family":"Green","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon H.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gail K.","family":"Adler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan S.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,14]]},"reference":[{"issue":"3","key":"587_CR1","doi-asserted-by":"publisher","first-page":"e28","DOI":"10.1161\/01.cir.0000441139.02102.80","volume":"129","author":"AS Go","year":"2014","unstructured":"Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics--2014 update: a report from the American Heart Association. Circulation. 2014;129(3):e28\u2013e292. https:\/\/doi.org\/10.1161\/01.cir.0000441139.02102.80.","journal-title":"Circulation."},{"key":"587_CR2","first-page":"1","volume":"177","author":"Q Gu","year":"2014","unstructured":"Gu Q, Paulose-Ram R, Burt VL, Kit BK. Prescription cholesterol-lowering medication use in adults aged 40 and over: United States, 2003-2012. NCHS Data Brief. 2014;177:1\u20138.","journal-title":"NCHS Data Brief"},{"issue":"9753","key":"587_CR3","doi-asserted-by":"publisher","first-page":"1670","DOI":"10.1016\/S0140-6736(10)61350-5","volume":"376","author":"C Baigent","year":"2010","unstructured":"Cholesterol Treatment Trialists\u2019 (CTT) Collaboration, Baigent C, Blackwell L, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670\u201381. https:\/\/doi.org\/10.1016\/S0140-6736(10)61350-5.","journal-title":"Lancet"},{"key":"587_CR4","doi-asserted-by":"publisher","first-page":"b2376","DOI":"10.1136\/bmj.b2376","volume":"338","author":"JJ Brugts","year":"2009","unstructured":"Brugts JJ, Yetgin T, Hoeks SE, et al. The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials. BMJ. 2009;338:b2376. https:\/\/doi.org\/10.1136\/bmj.b2376.","journal-title":"BMJ."},{"issue":"24","key":"587_CR5","doi-asserted-by":"publisher","first-page":"1536","DOI":"10.1093\/eurheartj\/ehv072","volume":"36","author":"D Preiss","year":"2015","unstructured":"Preiss D, Campbell RT, Murray HM, et al. The effect of statin therapy on heart failure events: a collaborative meta-analysis of unpublished data from major randomized trials. Eur Heart J. 2015;36(24):1536\u201346. https:\/\/doi.org\/10.1093\/eurheartj\/ehv072.","journal-title":"Eur Heart J"},{"issue":"8","key":"587_CR6","doi-asserted-by":"publisher","first-page":"1198","DOI":"10.1089\/ars.2013.5430","volume":"20","author":"M Margaritis","year":"2014","unstructured":"Margaritis M, Channon KM, Antoniades C. Statins as regulators of redox state in the vascular endothelium: beyond lipid lowering. Antioxid Redox Signal. 2014;20(8):1198\u2013215. https:\/\/doi.org\/10.1089\/ars.2013.5430.","journal-title":"Antioxid Redox Signal"},{"issue":"3","key":"587_CR7","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1161\/01.ATV.20.3.830","volume":"20","author":"BV Howard","year":"2000","unstructured":"Howard BV, Robbins DC, Sievers ML, Lee ET, Rhoades D, Devereux RB, Cowan LD, Gray RS, Welty TK, Go OT, et al. LDL cholesterol as a strong predictor of coronary heart disease in diabetic individuals with insulin resistance and low LDL: the strong heart study. Arterioscler Thromb Vasc Biol. 2000;20(3):830\u20135.","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"4","key":"587_CR8","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1161\/01.HYP.0000259737.43916.42","volume":"49","author":"P Strazzullo","year":"2007","unstructured":"Strazzullo P, Kerry SM, Barbato A, Versiero M, D\u2019Elia L, Cappuccio FP, et al. Do statins reduce blood pressure?: a meta-analysis of randomized, controlled trials. Hypertension. 2007;49(4):792\u20138. https:\/\/doi.org\/10.1161\/01.HYP.0000259737.43916.42.","journal-title":"Hypertension"},{"key":"587_CR9","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1007\/s11906-011-0182-2","volume":"13","author":"M Briet","year":"2011","unstructured":"Briet M, Schiffrin EL. The role of aldosterone in the metabolic syndrome. Curr Hypertens Rep. 2011;13:163\u201372.","journal-title":"Curr Hypertens Rep"},{"key":"587_CR10","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1007\/s11906-015-0567-8","volume":"17","author":"R Garg","year":"2015","unstructured":"Garg R, Adler GK. Aldosterone and the mineralocorticoid receptor: risk factors for cardiometabolic disorders. Curr Hypertens Rep. 2015;17:52.","journal-title":"Curr Hypertens Rep"},{"key":"587_CR11","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1007\/s11906-009-0076-8","volume":"11","author":"B Vogt","year":"2009","unstructured":"Vogt B, Burnier M. Aldosterone and cardiovascular risk. Curr Sci Inc. 2009;11:450\u20135. https:\/\/doi.org\/10.1007\/s11906-009-0076-8.","journal-title":"Curr Sci Inc"},{"issue":"5","key":"587_CR12","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1161\/HYPERTENSIONAHA.119.13922","volume":"75","author":"GK Adler","year":"2020","unstructured":"Adler GK, Murray GR, Turcu AF, et al. Primary Aldosteronism decreases insulin secretion and increases insulin clearance in humans. Hypertension. 2020;75(5):1251\u20139. https:\/\/doi.org\/10.1161\/HYPERTENSIONAHA.119.13922.","journal-title":"Hypertension"},{"issue":"19","key":"587_CR13","doi-asserted-by":"publisher","first-page":"1825","DOI":"10.1161\/CIRCULATIONAHA.115.016759","volume":"132","author":"R Baudrand","year":"2015","unstructured":"Baudrand R, Pojoga LH, Vaidya A, et al. Statin use and adrenal aldosterone production in hypertensive and diabetic participants. Circulation. 2015;132(19):1825\u201333. https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.115.016759.","journal-title":"Circulation"},{"key":"587_CR14","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/1472-6823-13-33","volume":"13","author":"JM Brown","year":"2013","unstructured":"Brown JM, et al. Evaluating hormonal mechanisms of vitamin D receptor agonist therapy in diabetic kidney disease: the VALIDATE-D study. 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Circulation. 2004;109(1). https:\/\/doi.org\/10.1161\/01.cir.0000131517.20177.5a.","DOI":"10.1161\/01.cir.0000131517.20177.5a"},{"key":"587_CR17","doi-asserted-by":"publisher","first-page":"2195","DOI":"10.1056\/NEJMoa0807646","volume":"359","author":"PM Ridker","year":"2008","unstructured":"Ridker PM, Danielson E, Fonseca FAH, Genest J, Gottto AM, Kastelein JJP, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ for the JUPITER study group. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. 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The Partners Human Research Committee will review and approve all protocol amendments, adverse events, and protocol deviations. A Data and Safety Monitoring Plan will include physician-investigators and lay representatives from the Cardiovascular Endocrinology Research Group who will review protocol deviations and adverse events monthly to ensure the integrity of the protocol and safety of participants. All participants will give written informed consent to participate, which will be obtained by a physician approved by the IRB to contribute to this protocol.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable. The manuscript does not contain data from any individual person.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"105"}}