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Mild primary aldosteronism (PA) followed by overt PA are possibly the most common forms of low renin hypertension: a single-center retrospective study

Journal of Human Hypertension volume 34, pages 633–640 (2020)Cite this article

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Abstract

Low renin hypertension (LRH) is a common condition in hypertensive patients, and mainly includes primary aldosteronism (PA) and low renin essential hypertension. To investigate the distributions and clinical manifestations of the main LRH forms, we reviewed 1267 hypertensive patients who underwent assessment for plasma renin activity (PRA) and plasma aldosterone concentration (PAC) by standardized protocols in our specialized center. LRH was defined as PRA < 1.0 ng/mL/h. A saline infusion test (SIT) was performed when LRH patients showed positive screening results for PA. The main LRH forms were defined as follows: post-SIT PAC > 10 ng/dL as ‘overt PA’, post-SIT PAC 5–10 ng/dL as ‘mild PA’, and post-SIT PAC < 5 ng/dL or negative screening results as ‘non-PA’. Overall, 760 patients were defined as LRH, with 160 classified as overt PA, 268 as mild PA, and 332 as non-PA. The total proportion of PA amounted to 56.3% with 21.0% overt PA and 35.3% mild PA. Compared with the mild PA, patients with overt PA had higher systolic and diastolic blood pressures, lower serum potassium, higher urine potassium excretion, more frequent incidence of stage 3 hypertension, hypokalemia, diabetes mellitus, and classical unilateral adenoma on computerized tomography (P < 0.05). PA including overt and mild forms is indeed a major form of LRH. Clinical manifestations in mild PA are less severe than those in overt PA. Nevertheless, mild PA is more prevalent than overt PA in LRH and should be recognized.

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References

  1. Laragh JH. Vasoconstriction-volume analysis for understanding and treating hypertension: the use of renin and aldosterone profiles. Am J Med. 1973;55:261–74.

    Article  CAS  Google Scholar 

  2. Ganguly A, Weinberger MH. Low renin hypertension: a current review of definitions and controversies. Am Heart J. 1979;98:642–52.

    Article  CAS  Google Scholar 

  3. Gordon RD, Laragh JH, Funder JW. Low renin hypertensive states: perspectives, unsolved problems, future research. Trends Endocrinol Metab. 2005;16:108–13.

    Article  CAS  Google Scholar 

  4. Monticone S, Burrello J, Tizzani D, Bertello C, Viola A, Buffolo F, et al. Prevalence and clinical manifestations of primary aldosteronism encountered in primary care practice. J Am Coll Cardiol. 2017;69:1811–20.

    Article  Google Scholar 

  5. Hannemann A, Wallaschofski K. Prevalence of primary aldosteronism in patient cohort and in population-based studies: a review of the current literature. Horm Metabol Res. 2012;44:157–62.

    Article  CAS  Google Scholar 

  6. Mulatero P, Verhovez A, Morello F, Veglio F. Diagnosis and treatment of low-renin hypertension. Clin Endocrinol. 2007;67:324–34.

    Article  CAS  Google Scholar 

  7. Adlin EV, Braitman LE, Vasan RS. Bimodal aldosterone distribution in low-renin hypertension. Am J Hypertens. 2013;26:1076–85.

    Article  CAS  Google Scholar 

  8. Baudrand R, Vaidya A. The low-renin hypertension phenotype: genetics and the role of the mineralocorticoid receptor. Int J Mol Sci. 2018;19:E546.

    Article  Google Scholar 

  9. Milliez P, Girerd X, Plouin PF, Blacher J, Safar ME, Mourad JJ. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol. 2005;45:1243–8.

    Article  CAS  Google Scholar 

  10. Mulatero P, Monticone S, Bertello C, Viola A, Tizzani D, Iannaccone A, et al. Long-term cardio- and cerebrovascular events in patients with primary aldosteronism. J Clin Endocrinol Metab. 2013;98:4826–33.

    Article  CAS  Google Scholar 

  11. Ohno Y, Sone M, Inagaki N, Yamasaki T, Ogawa O, Takeda Y, et al. Prevalence of cardiovascular disease and its risk factors in primary aldosteronism: a multicenter study in Japan. Hypertension. 2018;71:530–7.

    Article  CAS  Google Scholar 

  12. Giacchetti G, Mulatero P, Mantero F, Veglio F, Boscaro M, Fallo F. Primary aldosteronism, a major form of low renin hypertension: from screening to diagnosis. Trends Endocrinol Metab. 2008;19:104–8.

    Article  CAS  Google Scholar 

  13. Baudrand R, Guarda FJ, Fardella C, Hundemer G, Brown J, Williams G, et al. Continuum of renin-independent aldosteronism in normotension. Hypertension. 2017;69:950–6.

    Article  CAS  Google Scholar 

  14. Piaditis G, Markou A, Papanastasiou L, Androulakis II, Kaltsas G. Progress in aldosteronism: a review of the prevalence of primary aldosteronism in pre-hypertension and hypertension. Eur J Endocrinol. 2015;172:R191–203.

    Article  CAS  Google Scholar 

  15. Douma S, Petidis K, Doumas M, Papaefthimiou P, Triantafyllou A, Kartali N, et al. Prevalence of primary hyperaldosteronism in resistant hypertension: a retrospective observational study. Lancet. 2008;371:1921–6.

    Article  CAS  Google Scholar 

  16. Sywak M, Pasieka JL. Long-term follow-up and cost benefit of adrenalectomy in patients with primary hyperaldosteronism. Br J Surg. 2002;89:1587–93.

    Article  CAS  Google Scholar 

  17. Wu VC, Wang SM, Chang CH, Hu YH, Lin LY, Lin YH, et al. Long term outcome of Aldosteronism after target treatments. Sci Rep. 2016;6:32103.

    Article  CAS  Google Scholar 

  18. Stowasser M, Gordon RD. Primary aldosteronism–careful investigation is essential and rewarding. Mol Cell Endocrinol. 2004;217:33–9.

    Article  CAS  Google Scholar 

  19. Mosso L, Carvajal C, Gonzalez A, Barraza A, Avila F, Montero J, et al. Primary aldosteronism and hypertensive disease. Hypertension. 2003;42:161–5.

    Article  CAS  Google Scholar 

  20. Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, et al. Case detection, diagnosis, and treatment of patients with primary aldosteronism: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2008;93:3266–81.

    Article  CAS  Google Scholar 

  21. Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, et al. The management of primary aldosteronism: case detection, diagnosis, and treatment: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2016;101:1889–916.

    Article  CAS  Google Scholar 

  22. Käyser SC, Dekkers T, Groenewoud HJ, van der Wilt GJ, Carel Bakx J, van der Wel MC, et al. Study heterogeneity and estimation of prevalence of primary aldosteronism: a systematic review and meta-regression analysis. J Clin Endocrinol Metab. 2016;101:2826–35.

    Article  Google Scholar 

  23. Luo Q, Li NF, Yao XG, Zhang DL, Abulikemu SF, Chang GJ, et al. Potential effects of age on screening for primary aldosteronism. J Hum Hypertens. 2016;30:53–61.

    Article  Google Scholar 

  24. Rossi GP, Auchus RJ, Brown M, Lenders JW, Naruse M, Plouin PF, et al. An expert consensus statement on use of adrenal vein sampling for the subtyping of primary aldosteronism. Hypertension. 2014;63:151–60.

    Article  CAS  Google Scholar 

  25. The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Arch Intern Med. 1997;157:2413–46.

  26. Stowasser M, Ahmed AH, Cowley D, Wolley M, Guo Z, McWhinney BC, et al. Comparison of seated with recumbent saline suppression testing for the diagnosis of primary aldosteronism. J Clin Endocrinol Metab. 2018;103:4113–24.

    Article  Google Scholar 

  27. Brown JM, Robinson-Cohen C, Luque-Fernandez MA, Allison MA, Baudrand R, Ix JH, et al. The spectrum of subclinical primary aldosteronism and incident hypertension: a Cohort Study. Ann Intern Med. 2017;167:630–41.

    Article  Google Scholar 

  28. Markou A, Pappa T, Kaltsas G, Gouli A, Mitsakis K, Tsounas P, et al. Evidence of primary aldosteronism in a predominantly female cohort of normotensive individuals: a very high odds ratio for progression into arterial hypertension. J Clin Endocrinol Metab. 2013;98:1409–16.

    Article  CAS  Google Scholar 

  29. Heinrich DA, Adolf C, Rump LC, Quack I, Quinkler M, Hahner S, et al. Primary aldosteronism: key characteristics at diagnosis: a trend toward milder forms. Eur J Endocrinol. 2018;178:605–11.

    Article  CAS  Google Scholar 

  30. Omata K, Anand SK, Hovelson DH, Liu CJ, Yamazaki Y, Nakamura Y, et al. Aldosterone-producing cell clusters frequently harbor somatic mutations and accumulate with age in normal adrenals. J Endocr Soc. 2017;1:787–99.

    Article  CAS  Google Scholar 

  31. Omata K, Tomlins SA, Rainey WE. Aldosterone-producing cell clusters in normal and pathological states. Horm Metab Res. 2017;49:951–6.

    Article  CAS  Google Scholar 

  32. Weigel M, Riester A, Hanslik G, Lang K, Willenberg HS, Endres S, et al. Post-saline infusion test aldosterone levels indicate severity and outcome in primary aldosteronism. Eur J Endocrinol. 2015;172:443–50.

    Article  CAS  Google Scholar 

  33. Hayashi R, Tamada D, Murata M, Mukai K, Kitamura T, Otsuki M, et al. Saline Infusion Test highly associated with the incidence of cardio-and cerebrovascular events in primary aldosteronism. Endocr J. 2017;64:507–13.

    Article  Google Scholar 

  34. Ori Y, Chagnac A, Korzets A, Zingerman B, Herman-Edelstein M, Bergman M, et al. Regression of left ventricular hypertrophy in patients with primary aldosteronism/low-renin hypertension on low-dose spironolactone. Nephrol Dial Transpl. 2013;28:1787–93.

    Article  CAS  Google Scholar 

  35. Murata M, Kitamura T, Tamada D, Mukai K, Kurebayashi S, Yamamoto T, et al. Plasma aldosterone level within the normal range is less associated with cardiovascular and cerebrovascular risk in primary aldosteronism. J Hypertens. 2017;35:1079–85.

    Article  CAS  Google Scholar 

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Acknowledgements

This study was supported by Grant 81660139 from the National Natural Science Foundation of China and the non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences [2019PT330003]. No interventions were used in this study.

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Authors and Affiliations

  1. National Health Committee Key Laboratory of Hypertension Clinical Research, Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region; Hypertension Institute of Xinjiang, Urumqi, China

    Qin Luo, Nanfang Li, Menghui Wang, Xiaoguang Yao, Mulalibieke Heizhati, Delian Zhang, Keming Zhou, Guoliang Wang, Junli Hu & Bin Zhu

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  1. Qin Luo
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Correspondence to Nanfang Li.

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This study retrospectively analyzed data generated in a clinical process.

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This was a retrospective data analysis that did not require informed consent from participants. The ethical committee of our hospital approved the study design and data analysis.

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Luo, Q., Li, N., Wang, M. et al. Mild primary aldosteronism (PA) followed by overt PA are possibly the most common forms of low renin hypertension: a single-center retrospective study. J Hum Hypertens 34, 633–640 (2020). https://doi.org/10.1038/s41371-019-0291-y

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