Antihypertensive Pharmacological Therapy With Mineralocorticoid Receptor Antagonists in Obese Hypertensive Patients

Summary

Obesity is a complex metabolic state at which many pathophysiological pathways seem to interfere, like imbalance of autonomic nervous system, as well as renin-angiotensin-aldosterone system (RAAS) activation. Latest studies have shown that the increase of peripheral fat in obese patients, alongside with the increase of P-450 aromatase leads to hyper-aldosteronism, which results to increased sodium intake and rise of blood pressure. The present study aims to investigate the potential superiority of an aldosterone antagonist based therapy (eplerenone) over the renin-angiotensin antagonists (ARBs) (valsartan) based therapy in hypertensive obese patients regarding reduction of blood pressure (office, home and ambulatory) over a 24-week period.

Timeline

Start

2018-09-01

Primary completion

2025-06-30

Completion

2025-06-30

Publications

• Background Tsioufis C, Tsiachris D, Dimitriadis K, Thomopoulos C, Syrseloudis D, Andrikou E, Chatzis D, Taxiarchou E, Selima M, Mazaraki A, Chararis G, Tolis P, Gennadi A, Andrikou I, Stefanadi E, Fragoulis V, Tzamou V, Panagiotakos D, Tousoulis D, Stefanadis C. Leontio Lyceum ALbuminuria (3L Study) epidemiological study: aims, design and preliminary findings. Hellenic J Cardiol. 2009 Nov-Dec;50(6):476-83.
• Background Schlaich MP, Grassi G, Lambert GW, Straznicky N, Esler MD, Dixon J, Lambert EA, Redon J, Narkiewicz K, Jordan J; European Society of Hypertension Working Group on Obesity; Australian and New Zealand Obesity Society. European Society of Hypertension Working Group on Obesity Obesity-induced hypertension and target organ damage: current knowledge and future directions. J Hypertens. 2009 Feb;27(2):207-11. doi: 10.1097/HJH.0b013e32831dafaf. No abstract available.
• Background Dimitriadis K, Tsioufis C, Mazaraki A, Liatakis I, Koutra E, Kordalis A, Kasiakogias A, Flessas D, Tentolouris N, Tousoulis D. Waist circumference compared with other obesity parameters as determinants of coronary artery disease in essential hypertension: a 6-year follow-up study. Hypertens Res. 2016 Jun;39(6):475-9. doi: 10.1038/hr.2016.8. Epub 2016 Feb 11.
• Background Tsioufis CP, Tsiachris DL, Selima MN, Dimitriadis KS, Thomopoulos CG, Tsiliggiris DC, Gennadi AS, Syrseloudis DC, Stefanadi ES, Toutouzas KP, Kallikazaros IE, Stefanadis CI. Impact of waist circumference on cardiac phenotype in hypertensives according to gender. Obesity (Silver Spring). 2009 Jan;17(1):177-82. doi: 10.1038/oby.2008.462. Epub 2008 Oct 23.
• Background Jordan J, Yumuk V, Schlaich M, Nilsson PM, Zahorska-Markiewicz B, Grassi G, Schmieder RE, Engeli S, Finer N. Joint statement of the European Association for the Study of Obesity and the European Society of Hypertension: obesity and difficult to treat arterial hypertension. J Hypertens. 2012 Jun;30(6):1047-55. doi: 10.1097/HJH.0b013e3283537347.
• Background Badimon L, Bugiardini R, Cenko E, Cubedo J, Dorobantu M, Duncker DJ, Estruch R, Milicic D, Tousoulis D, Vasiljevic Z, Vilahur G, de Wit C, Koller A. Position paper of the European Society of Cardiology-working group of coronary pathophysiology and microcirculation: obesity and heart disease. Eur Heart J. 2017 Jul 1;38(25):1951-1958. doi: 10.1093/eurheartj/ehx181. No abstract available.
• Background Doll S, Paccaud F, Bovet P, Burnier M, Wietlisbach V. Body mass index, abdominal adiposity and blood pressure: consistency of their association across developing and developed countries. Int J Obes Relat Metab Disord. 2002 Jan;26(1):48-57. doi: 10.1038/sj.ijo.0801854.
• Background Mancia G, Bombelli M, Corrao G, Facchetti R, Madotto F, Giannattasio C, Trevano FQ, Grassi G, Zanchetti A, Sega R. Metabolic syndrome in the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study: daily life blood pressure, cardiac damage, and prognosis. Hypertension. 2007 Jan;49(1):40-7. doi: 10.1161/01.HYP.0000251933.22091.24. Epub 2006 Nov 27.
• Background Tsioufis C, Tatsis I, Thomopoulos C, Wilcox C, Palm F, Kordalis A, Katsiki N, Papademetriou V, Stefanadis C. Effects of hypertension, diabetes mellitus, obesity and other factors on kidney haemodynamics. Curr Vasc Pharmacol. 2014 May;12(3):537-48. doi: 10.2174/157016111203140518173700.
• Background Cushman WC, Ford CE, Cutler JA, Margolis KL, Davis BR, Grimm RH, Black HR, Hamilton BP, Holland J, Nwachuku C, Papademetriou V, Probstfield J, Wright JT Jr, Alderman MH, Weiss RJ, Piller L, Bettencourt J, Walsh SM; ALLHAT Collaborative Research Group. Success and predictors of blood pressure control in diverse North American settings: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). J Clin Hypertens (Greenwich). 2002 Nov-Dec;4(6):393-404. doi: 10.1111/j.1524-6175.2002.02045.x.
• Background Hall JE, Brands MW, Dixon WN, Smith MJ Jr. Obesity-induced hypertension. Renal function and systemic hemodynamics. Hypertension. 1993 Sep;22(3):292-9. doi: 10.1161/01.hyp.22.3.292.
• Background Engeli S, Negrel R, Sharma AM. Physiology and pathophysiology of the adipose tissue renin-angiotensin system. Hypertension. 2000 Jun;35(6):1270-7. doi: 10.1161/01.hyp.35.6.1270.
• Background de Paula RB, da Silva AA, Hall JE. Aldosterone antagonism attenuates obesity-induced hypertension and glomerular hyperfiltration. Hypertension. 2004 Jan;43(1):41-7. doi: 10.1161/01.HYP.0000105624.68174.00. Epub 2003 Nov 24.
• Background Garg R, Kneen L, Williams GH, Adler GK. Effect of mineralocorticoid receptor antagonist on insulin resistance and endothelial function in obese subjects. Diabetes Obes Metab. 2014 Mar;16(3):268-72. doi: 10.1111/dom.12224. Epub 2013 Oct 31.
• Background de Souza F, Muxfeldt E, Fiszman R, Salles G. Efficacy of spironolactone therapy in patients with true resistant hypertension. Hypertension. 2010 Jan;55(1):147-52. doi: 10.1161/HYPERTENSIONAHA.109.140988. Epub 2009 Oct 26.
• Background Vaclavik J, Sedlak R, Jarkovsky J, Kocianova E, Taborsky M. Effect of spironolactone in resistant arterial hypertension: a randomized, double-blind, placebo-controlled trial (ASPIRANT-EXT). Medicine (Baltimore). 2014 Dec;93(27):e162. doi: 10.1097/MD.0000000000000162.
• Background Williams B, MacDonald TM, Morant S, Webb DJ, Sever P, McInnes G, Ford I, Cruickshank JK, Caulfield MJ, Salsbury J, Mackenzie I, Padmanabhan S, Brown MJ; British Hypertension Society's PATHWAY Studies Group. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial. Lancet. 2015 Nov 21;386(10008):2059-2068. doi: 10.1016/S0140-6736(15)00257-3. Epub 2015 Sep 20.
• Background Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, Christiaens T, Cifkova R, De Backer G, Dominiczak A, Galderisi M, Grobbee DE, Jaarsma T, Kirchhof P, Kjeldsen SE, Laurent S, Manolis AJ, Nilsson PM, Ruilope LM, Schmieder RE, Sirnes PA, Sleight P, Viigimaa M, Waeber B, Zannad F; Task Force Members. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013 Jul;31(7):1281-357. doi: 10.1097/01.hjh.0000431740.32696.cc. No abstract available.

Drugs

Indications