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DOI: 10.1055/a-2035-6179
Association of Aldosterone with Mortality in the General Population
Funding Information German Research Foundation — RA-45913/3–1, CRC/TRR 205 “The Adrenal Gland”; European Research Council under the European Union’s Horizon 2020 research and innovation programme — grant agreement No 694913; Else Kröner-Fresenius Stiftung — 2012_A103, 2015_A228, 2019_A104; German Center for Diabetes Research e.V. (DZD); Federal Ministry of Health (Berlin, Germany); Ministry of Culture and Science of the state North Rhine Westphalia (Düsseldorf, Germany); Virtual Diabetes Institute (Helmholtz Zentrum München); German Federal Ministry of Education and Research (BMBF); State of Bavaria; German Diabetes Center.
Abstract
Introduction Aldosterone excess is linked to cardiovascular events and mortality as well as to low-grade inflammation in the context of metabolic diseases. Whether mildly elevated aldosterone levels in the general population promote cardiovascular risk is still under debate. We analyzed the association of plasma aldosterone concentrations with incident cardiovascular events, cardiovascular and all-cause mortality as well as with biomarkers of subclinical inflammation in the population-based KORA F4 study.
Methods Plasma aldosterone concentrations were measured with an in-house immunoflurometric assay. The analyses included 2935 participants (n=1076 for selected biomarkers of subclinical inflammation) with a median follow-up of 8.7 (8.2; 9.1) years. The associations were estimated using Cox proportional hazard and linear regression models adjusted for renin, sex, age, body mass index, arterial hypertension, diabetes, estimated glomerular filtration rate, low- and high-density lipoprotein cholesterol, physical activity, smoking, use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, diuretics and calcium channel blockers.
Results Aldosterone was significantly associated with all-cause mortality (hazard ratio per standard deviation increase: 1.20; 95% confidence interval 1.04–1.37), but not with cardiovascular mortality, incident cardiovascular events, or with biomarkers of subclinical inflammation.
Conclusions Aldosterone was associated with all-cause mortality in the population-based KORA F4 study, but the previously described associations of excess aldosterone with cardiovascular complications and biomarkers of subclinical inflammation could not be shown.
* Contributed equally: Annette Peters, Martin Reincke
Publication History
Received: 19 December 2022
Received: 31 January 2023
Accepted: 07 February 2023
Accepted Manuscript online:
14 February 2023
Article published online:
20 March 2023
© 2023. Thieme. All rights reserved.
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References
- 1 Funder JW, Reincke M.. Aldosterone: A cardiovascular risk factor?. Biochim Biophys Acta 2010; 1802: 1188-1192
- 2 Güder G, Bauersachs J, Frantz S. et al. Complementary and incremental mortality risk prediction by cortisol and aldosterone in chronic heart failure. Circulation 2007; 115: 1754-1761
- 3 Reincke M, Bancos I, Mulatero P. et al. Diagnosis and treatment of primary aldosteronism. Lancet Diabetes Endocrinol 2021; 9: 876-892
- 4 Reincke M, Fischer E, Gerum S. et al. Observational study mortality in treated primary aldosteronism: The German Conn’s registry. Hypertens (Dallas, Tex 1979) 2012; 60: 618-624
- 5 Hundemer GL, Curhan GC, Yozamp N. et al. Cardiometabolic outcomes and mortality in medically treated primary aldosteronism: A retrospective cohort study. Lancet Diabetes Endocrinol 2018; 6: 51-59
- 6 Tomaschitz A, Pilz S, Ritz E. et al. Plasma aldosterone levels are associated with increased cardiovascular mortality: The Ludwigshafen Risk and Cardiovascular Health (LURIC) study. Eur Heart J 2010; 31: 1237-1247
- 7 Ivanes F, Susen S, Mouquet F. et al. Aldosterone, mortality, and acute ischaemic events in coronary artery disease patients outside the setting of acute myocardial infarction or heart failure. Eur Heart J 2012; 33: 191-202
- 8 Hillaert MA, Lentjes EG, Kemperman H. et al. Aldosterone, atherosclerosis and vascular events in patients with stable coronary artery disease. Int J Cardiol 2013; 167: 1929-1935
- 9 Beygui F, Montalescot G, Vicaut E. et al. Aldosterone and long-term outcome after myocardial infarction: A substudy of the french nationwide Observatoire sur la Prise en charge hospitalière, l’Evolution à un an et les caRactéristiques de patients présentant un infArctus du myocarde avec ou sans onde Q (OPERA) study. Am Heart J 2009; 157: 680-687
- 10 Pitt B, Zannad F, Remme WJ. et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999; 341: 709-717
- 11 Pitt B, Gheorghiade M, Zannad F. et al. Evaluation of eplerenone in the subgroup of EPHESUS patients with baseline left ventricular ejection fraction. Eur J Heart Fail 2006; 8: 295-301
- 12 Pitt B, Remme W, Zannad F. et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 2003; 348: 1309-1321
- 13 Chen Q, Zhao D, Sun J. et al. Aldosterone blockade in acute myocardial infarction: A systematic review and meta-analysis. Cardiovasc Ther 2021; 2021
- 14 Hayashi M, Tsutamoto T, Wada A. et al. Immediate administration of mineralocorticoid receptor antagonist spironolactone prevents post-infarct left ventricular remodeling associated with suppression of a marker of myocardial collagen synthesis in patients with first anterior acute myocardial infarction. Circulation 2003; 107: 2559-2565
- 15 Fraccarollo D, Berger S, Galuppo P. et al. Deletion of cardiomyocyte mineralocorticoid receptor ameliorates adverse remodeling after myocardial infarction. Circulation 2011; 123: 400-408
- 16 McGraw AP, Bagley J, Chen WS. et al. Aldosterone increases early atherosclerosis and promotes plaque inflammation through a placental growth factor-dependent mechanism. J Am Heart Assoc 2013; 2
- 17 Marzolla V, Armani A, Mammi C. et al. Essential role of ICAM-1 in aldosterone-induced atherosclerosis. Int J Cardiol 2017; 232: 233-242
- 18 Caprio M, Newfell BG, La Sala A. et al. Functional mineralocorticoid receptors in human vascular endothelial cells regulate intercellular adhesion molecule-1 expression and promote leukocyte adhesion. Circ Res 2008; 102: 1359-1367
- 19 Chou CH, Hung CS, Liao CW. et al. IL-6 trans-signalling contributes to aldosterone-induced cardiac fibrosis. Cardiovasc Res 2018; 114: 690-702
- 20 Wu C, Zhang H, Zhang J. et al. Inflammation and fibrosis in perirenal adipose tissue of patients with aldosterone-producing adenoma. Endocrinology 2018; 159: 227-237
- 21 Ferreira NS, Tostes RC, Paradis P. et al. Aldosterone, inflammation, immune system, and hypertension. Am J Hypertens 2021; 34: 15-27
- 22 Huth C, von Toerne C, Schederecker F. et al. Protein markers and risk of type 2 diabetes and prediabetes: A targeted proteomics approach in the KORA F4/FF4 study. Eur J Epidemiol 2019; 34: 409-422
- 23 Then C, Sujana C, Herder C. et al. Association of C-terminal pro-endothelin-1 with mortality in the population-based KORA F4 Study. Vasc Health Risk Manag 2022; 18: 335-346
- 24 Manolopoulou J, Bielohuby M, Caton SJ. et al. A highly sensitive immunofluorometric assay for the measurement of aldosterone in small sample volumes: Validation in mouse serum. J Endocrinol 2008; 196: 215-224
- 25 Hsieh FY, Lavori PW.. Sample-size calculations for the Cox proportional hazards regression model with nonbinary covariates. Control Clin Trials 2000; 21: 552-560
- 26 Buglioni A, Cannone V, Cataliotti A. et al. Circulating aldosterone and natriuretic peptides in the general community relationship to cardiorenal and metabolic disease. Hypertension 2015; 65: 45-53
- 27 Daimon M, Konta T, Oizumi T. et al. Lower aldosterone-renin ratio is a risk factor for total and cancer death in Japanese individuals: The Takahata study. Clin Endocrinol (Oxf) 2015; 82: 489-496
- 28 Daimon M, Konta T, Oizumi T. et al. Higher plasma renin activity is a risk factor for total mortality in older Japanese individuals: The Takahata study. Metabolism 2012; 61: 504-511
- 29 Deo R, Yang W, Khan AM. et al. Serum aldosterone and death, end-stage renal disease, and cardiovascular events in blacks and whites: Findings from the chronic renal insufficiency cohort (CRIC) study. Hypertension 2014; 64: 103-110
- 30 Tomaschitz A, Pilz S, Ritz E. et al. Association of plasma aldosterone with cardiovascular mortality in patients with low estimated GFR: the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study. Am J Kidney Dis 2011; 57: 403-414
- 31 Schäfer N, Lohmann C, Winnik S. et al. Endothelial mineralocorticoid receptor activation mediates endothelial dysfunction in diet-induced obesity. Eur Heart J 2013; 34: 3515-3524
- 32 Jia G, Habibi J, Aroor AR. et al. Endothelial mineralocorticoid receptor mediates diet-induced aortic stiffness in females. Circ Res 2016; 118: 935-943
- 33 Li W, Chen X, Riley AM. et al. Long-term spironolactone treatment reduces coronary TRPC expression, vasoconstriction, and atherosclerosis in metabolic syndrome pigs. Basic Res Cardiol 2017; 112
- 34 Silvestre JS, Heymes C, Oubénaïssa A. et al. Activation of cardiac aldosterone production in rat myocardial infarction: Effect of angiotensin II receptor blockade and role in cardiac fibrosis. Circulation 1999; 99: 2694-2701
- 35 Mizuno Y, Yoshimura M, Yasue H. et al. Aldosterone production is activated in failing ventricle in humans. Circulation 2001; 103: 72-77