Download PDF
Horm Metab Res 2020; 52(06): 366-372
DOI: 10.1055/a-1133-7255
Review

Primary Aldosteronism and Obstructive Sleep Apnea: Casual Association or Pathophysiological Link?

Alessio Pecori
1   Division of Internal Medicine 4 and Hypertension Unit, Department of Medical Sciences, University of Torino, Torino, Italy
,
Fabrizio Buffolo
1   Division of Internal Medicine 4 and Hypertension Unit, Department of Medical Sciences, University of Torino, Torino, Italy
,
Jacopo Pieroni
1   Division of Internal Medicine 4 and Hypertension Unit, Department of Medical Sciences, University of Torino, Torino, Italy
,
Vittorio Forestiero
1   Division of Internal Medicine 4 and Hypertension Unit, Department of Medical Sciences, University of Torino, Torino, Italy
,
Elisa Sconfienza
1   Division of Internal Medicine 4 and Hypertension Unit, Department of Medical Sciences, University of Torino, Torino, Italy
,
Franco Veglio
1   Division of Internal Medicine 4 and Hypertension Unit, Department of Medical Sciences, University of Torino, Torino, Italy
,
Paolo Mulatero 
1   Division of Internal Medicine 4 and Hypertension Unit, Department of Medical Sciences, University of Torino, Torino, Italy
,
Silvia Monticone
1   Division of Internal Medicine 4 and Hypertension Unit, Department of Medical Sciences, University of Torino, Torino, Italy
› Author Affiliations
› Further Information
Also available at
   Permissions and Reprints

Abstract

The coexistence of aldosterone oversecretion and obstructive sleep apnea is frequently observed, especially in patients with resistant hypertension, obesity, and metabolic syndrome. Since aldosterone excess and sleep apnea are both independently associated with an increased risk of cardiovascular disease, to investigate whether their coexistence might be attributed to common predisposing conditions, such as metabolic disorders, or to an actual pathophysiological interconnection appears of great importance. Fluid overload and metabolic abnormalities relating to aldosterone oversecretion may be implicated in obstructive sleep apnea development. Nocturnal intermittent hypoxia may in turn exacerbate renin-angiotensin-aldosterone system activity, thus leading to hyperaldosteronism. Furthermore, fat tissue excess and adipocyte secretory products might predispose to both sleep apnea and aldosterone oversecretion in subjects with obesity. Consistent with these evidences, obstructive sleep apnea frequently affects patients with primary aldosteronism. Conversely, whether primary aldosteronism is more prevalent in individuals affected by obstructive sleep apnea compared to the general population remains controversial.

Key words

aldosterone - sleep disorders - obesity - metabolic syndrome - apnea-hypopnea index - leptin


Publication History

Received: 18 December 2019

Accepted: 26 February 2020

Article published online:
27 March 2020

© Georg Thieme Verlag KG
Stuttgart · New York

 

  • References

  • 1 Pimenta E, Calhoun DA, Oparil S. Sleep apnea, aldosterone, and resistant hypertension. Prog Cardiovasc Dis 2009; 51: 371-380
    CrossrefPubMedGoogle Scholar
  • 2 Martínez-García M-A, Navarro-Soriano C, Torres G. et al. Beyond resistant hypertension. Hypertension 2018; 72: 618-624
    CrossrefPubMedGoogle Scholar
  • 3 Calhoun DA, Nishizaka MK, Zaman MA. et al. Hyperaldosteronism among black and white subjects with resistant hypertension. Hypertension 2002; 40: 892-896
    CrossrefPubMedGoogle Scholar
  • 4 Daugherty SL, Powers JD, Magid DJ. et al. Incidence and prognosis of resistant hypertension in hypertensive patients. Circulation 2012; 125: 1635-1642
    CrossrefPubMedGoogle Scholar
  • 5 Calhoun DA, Nishizaka MK, Zaman MA. et al. Aldosterone excretion among subjects with resistant hypertension and symptoms of sleep apnea. Chest 2004; 125: 112-117
    CrossrefPubMedGoogle Scholar
  • 6 Di Murro A, Petramala L, Cotesta D. et al. Renin-angiotensin-aldosterone system in patients with sleep apnoea: Prevalence of primary aldosteronism. J Renin Angiot Aldoster Syst 2010; 11: 165-172
    CrossrefPubMedGoogle Scholar
  • 7 Funder JW, Carey RM, Mantero F. et al. The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2016; 101: 1889-1916
    CrossrefPubMedGoogle Scholar
  • 8 Prejbisz A, Kolodziejczyk-Kruk S, Lenders JWM. et al. Primary Aldosteronism and Obstructive Sleep Apnea: Is this a Bidirectional Relationship?. Horm Metab Res 2017; 49: 969-976
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Mulatero P, Tizzani D, Viola A. et al. Prevalence and Characteristics of Familial Hyperaldosteronism. Hypertension 2011; 58: 797-803
    CrossrefPubMedGoogle Scholar
  • 10 Monticone S, D'Ascenzo F, Moretti C. et al. Cardiovascular events and target organ damage in primary aldosteronism compared with essential hypertension: A systematic review and meta-analysis. Lancet Diabetes Endocrinol 2018; 6: 41-50
    CrossrefPubMedGoogle Scholar
  • 11 Monticone S, Sconfienza E, D’Ascenzo F. et al. Renal damage in primary aldosteronism: A systematic review and meta-analysis. J Hypertens 2020; 38: 3-12
    CrossrefPubMedGoogle Scholar
  • 12 Monticone S, Burrello J, Tizzani D. et al. Prevalence and clinical manifestations of primary aldosteronism encountered in primary care practice. J Am Coll Cardiol 2017; 69: 1811-1820
    CrossrefPubMedGoogle Scholar
  • 13 Rossi GP, Bernini G, Caliumi C. et al. A prospective study of the prevalence of primary aldosteronism in 1125 hypertensive patients. J Am Coll Cardiol 2006; 48: 2293-2300
    CrossrefPubMedGoogle Scholar
  • 14 Buffolo F, Li Q, Monticone S. et al. Primary aldosteronism and obstructive sleep apnea: a cross-sectional multi-ethnic study. Hypertension 2019; 74: 1532-1540
    CrossrefPubMedGoogle Scholar
  • 15 Somers VK, White DP, Amin R. et al. Sleep apnea and cardiovascular disease: An American Heart Association/american College of Cardiology Foundation Scientific Statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council on Cardiovascular Nursing. In collaboration with the National Heart, Lung, and Blood Institute National Center on Sleep Disorders Research (National Institutes of Health). Circulation 2008; 118: 1080-1111
    CrossrefPubMedGoogle Scholar
  • 16 Marin JM, Agusti A, Villar I. et al. Association between treated and untreated obstructive sleep apnea and risk of hypertension. JAMA 2012; 307: 2169-2176
    CrossrefPubMedGoogle Scholar
  • 17 Peppard PE, Young T, Palta M. et al. Prospective study of the association between sleep-disordered breathing and hypertension. N Eng J Med 2000; 342: 1378-1384
    CrossrefPubMedGoogle Scholar
  • 18 Williams B, Mancia G, Spiering W. et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J 2018; 39: 3021-3104
    CrossrefPubMedGoogle Scholar
  • 19 Marin JM, Carrizo SJ, Vicente E. et al. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet 2005; 365: 1046-1053
    CrossrefPubMedGoogle Scholar
  • 20 Redline S, Foody J. Sleep disturbances: time to join the top 10 potentially modifiable cardiovascular risk factors?. Circulation 2011; 124: 2049-2051
    CrossrefPubMedGoogle Scholar
  • 21 Gami AS, Olson EJ, Shen WK. et al. Obstructive sleep apnea and the risk of sudden cardiac death: A longitudinal study of 10 701 adults. J Am Coll Cardiol 2013; 62: 610-616
    PubMedGoogle Scholar
  • 22 Senaratna CV, Perret JL, Lodge CJ. et al. Prevalence of obstructive sleep apnea in the general population: A systematic review. Sleep Med Rev 2017; 34: 70-81
    CrossrefPubMedGoogle Scholar
  • 23 Heinzer R, Vat S, Marques-Vidal P. et al. Prevalence of sleep-disordered breathing in the general population: the HypnoLaus study. Lancet Resp Med 2015; 3: 310-318
    CrossrefPubMedGoogle Scholar
  • 24 Drager LF, Togeiro SM, Polotsky VY. et al. Obstructive sleep apnea: A cardiometabolic risk in obesity and the metabolic syndrome. J Am Coll Cardiol 2013; 62: 569-576
    Google Scholar
  • 25 Ahmad M, Makati D, Akbar S. Review of and updates on hypertension in obstructive sleep apnea. Int J Hypertens. 2017 1848375.
    PubMedGoogle Scholar
  • 26 Ke X, Guo W, Peng H. et al. Association of aldosterone excess and apnea-hypopnea index in patients with resistant hypertension. Sci Rep 2017; 7: 45241
    CrossrefPubMedGoogle Scholar
  • 27 Lloberes P, Lozano L, Sampol G. et al. Obstructive sleep apnoea and 24-h blood pressure in patients with resistant hypertension. J Sleep Res 2010; 19: 597-602
    CrossrefPubMedGoogle Scholar
  • 28 Sim JJ, Yan EH, Liu IL. et al. Positive relationship of sleep apnea to hyperaldosteronism in an ethnically diverse population. J Hypertens 2011; 29: 1553-1559
    CrossrefPubMedGoogle Scholar
  • 29 Florczak E, Prejbisz A, Szwench-Pietrasz E. et al. Clinical characteristics of patients with resistant hypertension: the RESIST-POL study. J Hum Hypertens 2013; 27: 678-685
    CrossrefPubMedGoogle Scholar
  • 30 Wolley MJ, Pimenta E, Calhoun D. et al. Treatment of primary aldosteronism is associated with a reduction in the severity of obstructive sleep apnoea. J Hum Hypertens 2017; 31: 561-567
    CrossrefPubMedGoogle Scholar
  • 31 Chen X, Wang R, Zee P. et al. Racial/Ethnic Differences in Sleep Disturbances: The Multi-Ethnic Study of Atherosclerosis (MESA). Sleep 2015; 38: 877-888
    PubMedGoogle Scholar
  • 32 Ip MS, Lam B, Lauder IJ. et al. A community study of sleep-disordered breathing in middle-aged Chinese men in Hong Kong. Chest 2001; 119: 62-69
    CrossrefPubMedGoogle Scholar
  • 33 Ip MS, Lam B, Tang LC. et al. A community study of sleep-disordered breathing in middle-aged Chinese women in Hong Kong: prevalence and gender differences. Chest 2004; 125: 127-134
    CrossrefPubMedGoogle Scholar
  • 34 Kario K, Chen CH, Park S. et al. Consensus Document on Improving Hypertension Management in Asian Patients, Taking Into Account Asian Characteristics. Hypertension 2018; 71: 375-382
    CrossrefPubMedGoogle Scholar
  • 35 Cai A, Zhou Y, Zhang J. et al. Epidemiological characteristics and gender-specific differences of obstructive sleep apnea in a Chinese hypertensive population: A cross-sectional study. BMC Cardiovasc Disord 2017; 17: 8
    CrossrefPubMedGoogle Scholar
  • 36 Ancoli-Israel S, Klauber MR, Stepnowsky C. et al. Sleep-disordered breathing in African-American elderly. Am J Resp Crit Care Med 1995; 152: 1946-1949
    CrossrefPubMedGoogle Scholar
  • 37 Redline S, Tishler PV, Hans MG. et al. Racial differences in sleep-disordered breathing in African-Americans and Caucasians. Am J Resp Crit Care Med 1997; 155: 186-192
    CrossrefPubMedGoogle Scholar
  • 38 Tu W, Eckert GJ, Pratt JH. et al. Plasma levels of prorenin and renin in blacks and whites: their relative abundance and associations with plasma aldosterone concentration. Am J Hypertens 2012; 25: 1030-1034
    CrossrefPubMedGoogle Scholar
  • 39 Nishizaka MK, Pratt-Ubunama M, Zaman MA. et al. Validity of Plasma Aldosterone-to-Renin Activity Ratio in African American and White Subjects With Resistant Hypertension. Am J Hypertens 2005; 18: 805-812
    CrossrefPubMedGoogle Scholar
  • 40 Johnson DA, Thomas SJ, Abdalla M. et al. Association between sleep apnea and blood pressure control among blacks. Circulation 2019; 139: 1275-1284
    CrossrefPubMedGoogle Scholar
  • 41 Gonzaga C, Bertolami A, Bertolami M. et al. Obstructive sleep apnea, hypertension and cardiovascular diseases. J Hum Hypertens 2015; 29: 705-712
    CrossrefPubMedGoogle Scholar
  • 42 Soltysiak M, Miazgowski T, Jaroszyńska E. et al. Impaired aldosterone response to the saline infusion test in patients with resistant hypertension and obstructive sleep apnea. Nadcisn Tetn 2015; 19: 13-18
    PubMedGoogle Scholar
  • 43 Yang S-j, Jiang X-T, Zhang X-B. et al. Does continuous positive airway pressure reduce aldosterone levels in patients with obstructive sleep apnea?. Sleep Breath 2016; 20: 921-928
    CrossrefPubMedGoogle Scholar
  • 44 Moller DS, Lind P, Strunge B. et al. Abnormal vasoactive hormones and 24-hour blood pressure in obstructive sleep apnea. Am J Hypertens 2003; 16: 274-280
    CrossrefPubMedGoogle Scholar
  • 45 Zhang J, Tian L, Guo L. Changes of aldosterone levels in patients with type 2 diabetes complicated by moderate to severe obstructive sleep apnea-hypopnea syndrome before and after treatment with continuous positive airway pressure. J Int Med Res 2019; 47: 4723-4733
    CrossrefPubMedGoogle Scholar
  • 46 de Souza F, Muxfeldt ES, Margallo V. et al. Effects of continuous positive airway pressure treatment on aldosterone excretion in patients with obstructive sleep apnoea and resistant hypertension: a randomized controlled trial. J Hypertens 2017; 35: 837-844
    CrossrefPubMedGoogle Scholar
  • 47 Casitas R, Martínez-Cerón E, Galera R. et al. The effect of treatment for sleep apnoea on determinants of blood pressure control. Eur Resp J 2017; 50: 1701261
    CrossrefPubMedGoogle Scholar
  • 48 Thunström E, Manhem K, Yucel-Lindberg T. et al. Neuroendocrine and inflammatory responses to losartan and continuous positive airway pressure in patients with hypertension and obstructive sleep apnea. a randomized controlled trial. Ann Am Thor Soc 2016; 13: 2002-2011
    CrossrefPubMedGoogle Scholar
  • 49 Perger E, Jutant EM, Redolfi S. Targeting volume overload and overnight rostral fluid shift: A new perspective to treat sleep apnea. Sleep Med Rev 2018; 42: 160-170
    CrossrefPubMedGoogle Scholar
  • 50 Kasai T, Bradley TD, Friedman O. et al. Effect of intensified diuretic therapy on overnight rostral fluid shift and obstructive sleep apnoea in patients with uncontrolled hypertension. J Hypertens 2014; 32: 673-680
    CrossrefPubMedGoogle Scholar
  • 51 Dudenbostel T, Calhoun DA. Resistant hypertension, obstructive sleep apnoea and aldosterone. J Hum Hypertens 2012; 26: 281-287
    CrossrefPubMedGoogle Scholar
  • 52 Jin ZN, Wei YX. Meta-analysis of effects of obstructive sleep apnea on the renin-angiotensin-aldosterone system. J Geriat Cardiol 2016; 13: 333-343
    PubMedGoogle Scholar
  • 53 Muxfeldt ES, Margallo VS, Guimaraes GM. et al. Prevalence and associated factors of obstructive sleep apnea in patients with resistant hypertension. Am J Hypertens 2014; 27: 1069-1078
    CrossrefPubMedGoogle Scholar
  • 54 Pratt-Ubunama MN, Nishizaka MK, Boedefeld RL. et al. Plasma aldosterone is related to severity of obstructive sleep apnea in subjects with resistant hypertension. Chest 2007; 131: 453-459
    CrossrefPubMedGoogle Scholar
  • 55 Gonzaga CC, Gaddam KK, Ahmed MI. et al. Severity of obstructive sleep apnea is related to aldosterone status in subjects with resistant hypertension. J Clin Sleep Med 2010; 6: 363-368
    CrossrefPubMedGoogle Scholar
  • 56 Pimenta E, Stowasser M, Gordon RD. et al. Increased dietary sodium is related to severity of obstructive sleep apnea in patients with resistant hypertension and hyperaldosteronism. Chest 2013; 143: 978-983
    CrossrefPubMedGoogle Scholar
  • 57 Gaddam K, Pimenta E, Thomas SJ. et al. Spironolactone reduces severity of obstructive sleep apnoea in patients with resistant hypertension: A preliminary report. J Hum Hypertens 2010; 24: 532-537
    CrossrefPubMedGoogle Scholar
  • 58 Krasinska B, Miazga A, Cofta S. et al. Effect of eplerenone on the severity of obstructive sleep apnea and arterial stiffness in patients with resistant arterial hypertension. Pol Arch Med Wewnet 2016; 126: 330-339
    PubMedGoogle Scholar
  • 59 Yang L, Zhang H, Cai M. et al. Effect of spironolactone on patients with resistant hypertension and obstructive sleep apnea. Clin Exp Hypertens 2016; 38: 464-468
    CrossrefPubMedGoogle Scholar
  • 60 Zhang ZH, Yu Y, Kang YM. et al. Aldosterone acts centrally to increase brain renin-angiotensin system activity and oxidative stress in normal rats. American Journal of Physiology. Heart Circul Physiol 2008; 294: H1067-H1074
    CrossrefPubMedGoogle Scholar
  • 61 Monticone S, Viola A, Tizzani D. et al. Primary aldosteronism: Who should be screened?. Horm Metab Res 2012; 44: 163-169
    Article in Thieme ConnectPubMedGoogle Scholar
  • 62 Ip MS, Lam B, Ng MM. et al. Obstructive sleep apnea is independently associated with insulin resistance. Am J Resp. Crit Care Med 2002; 165: 670-676
    CrossrefPubMedGoogle Scholar
  • 63 Kim NH. Obstructive sleep apnea and abnormal glucose metabolism. Diabetes Metab J 2012; 36: 268-272
    CrossrefPubMedGoogle Scholar
  • 64 Reutrakul S, Mokhlesi B. Obstructive sleep apnea and diabetes: A state of the art review. Chest 2017; 152: 1070-1086
    CrossrefPubMedGoogle Scholar
  • 65 Barcelo A, Pierola J, Esquinas C. et al. Relationship between aldosterone and the metabolic syndrome in patients with obstructive sleep apnea hypopnea syndrome: Effect of continuous positive airway pressure treatment. PloS One 2014; 9: e84362
    CrossrefPubMedGoogle Scholar
  • 66 Lamounier-Zepter V, Bornstein SR, Ehrhart-Bornstein M. Mechanisms of obesity-related hypertension. Horm Metab Res 2004; 36: 376-380
    Article in Thieme ConnectPubMedGoogle Scholar
  • 67 Rocchini AP, Katch VL, Grekin R. et al. Role for aldosterone in blood pressure regulation of obese adolescents. Am J Cardiol 1986; 57: 613-618
    CrossrefPubMedGoogle Scholar
  • 68 Engeli S, Bohnke J, Gorzelniak K. et al. Weight loss and the renin-angiotensin-aldosterone system. Hypertension 2005; 45: 356-362
    CrossrefPubMedGoogle Scholar
  • 69 Dudenbostel T, Ghazi L, Liu M. et al. Body mass index predicts 24-hour urinary aldosterone levels in patients with resistant hypertension. Hypertension 2016; 68: 995-1003
    CrossrefPubMedGoogle Scholar
  • 70 Li L, Hou X, Geng X. et al. Body mass index predicts aldosterone production in hypertensive postmenopausal women. Clin Exp Hypertens 2019; 1-6
    PubMedGoogle Scholar
  • 71 Massiera F, Bloch-Faure M, Ceiler D. et al. Adipose angiotensinogen is involved in adipose tissue growth and blood pressure regulation. FASEB J 2001; 15: 2727-2729
    CrossrefPubMedGoogle Scholar
  • 72 Goodfriend TL. Obesity, sleep apnea, aldosterone, and hypertension. Curr Hypertens Rep 2008; 10: 222-226
    CrossrefPubMedGoogle Scholar
  • 73 Ehrhart-Bornstein M, Lamounier-Zepter V, Schraven A. et al. Human adipocytes secrete mineralocorticoid-releasing factors. Proc Natl Acad Sci USA 2003; 100: 14211-14216
    CrossrefPubMedGoogle Scholar
  • 74 Jeon JH, Kim K-y, Kim JH. et al. A novel adipokine CTRP1 stimulates aldosterone production. FASEB J 2008; 22: 1502-1511
    CrossrefPubMedGoogle Scholar
  • 75 Xie D, Bollag WB. Obesity, hypertension and aldosterone: Is leptin the link?. J Endocrinol 2016; 230: F7-F11
    CrossrefPubMedGoogle Scholar
  • 76 Huby AC, Antonova G, Groenendyk J. et al. Adipocyte-derived hormone leptin is a direct regulator of aldosterone secretion, which promotes endothelial dysfunction and cardiac fibrosis. Circulation 2015; 132: 2134-2145
    CrossrefPubMedGoogle Scholar
  • 77 Faulkner JL, Belin de Chantemele EJ. Sex differences in mechanisms of hypertension associated with obesity. Hypertension 2018; 71: 15-21
    CrossrefPubMedGoogle Scholar
  • 78 Haluzik M, Sindelka G, Widimsky J. et al. Serum leptin levels in patients with primary hyperaldosteronism before and after treatment: Relationships to insulin sensitivity. J Hum Hypertens 2002; 16: 41-45
    CrossrefPubMedGoogle Scholar
  • 79 Torpy DJ, Bornstein SR, Taylor W. et al. Leptin levels are suppressed in primary aldosteronism. Horm Metab Res 1999; 31: 533-536
    Article in Thieme ConnectPubMedGoogle Scholar
  • 80 Ohno Y, Sone M, Inagaki N. et al. Obesity as a key factor underlying idiopathic hyperaldosteronism. J Clin Endocrinol Metab 2018; 103: 4456-4464
    CrossrefPubMedGoogle Scholar
  • 81 Shibayama Y, Wada N. Relationship Between Visceral Fat and Plasma Aldosterone Concentration in Patients With Primary Aldosteronism. J Endocr Soc 2018; 2: 1236-1245
    CrossrefPubMedGoogle Scholar
  • 82 Kalil GZ, Haynes WG. Sympathetic nervous system in obesity-related hypertension: Mechanisms and clinical implications. Hypertens Res 2012; 35: 4-16
    CrossrefPubMedGoogle Scholar
  • 83 Fallo F, Veglio F, Bertello C. et al. Prevalence and characteristics of the metabolic syndrome in primary aldosteronism. J Clin Endocrinol Metab 2006; 91: 454-459
    CrossrefPubMedGoogle Scholar
  • 84 Bothou C, Beuschlein F, Spyroglou A. Links between aldosterone excess and metabolic complications: A comprehensive review. Diabetes Metab 2020; 46: 1-7
    CrossrefPubMedGoogle Scholar
  • 85 Beuschlein F, Reincke M, Arlt W. The impact of Connshingʼs syndrome - mild cortisol excess in primary aldosteronism drives diabetes risk. J Hypertens 2017; 35: 2548
    CrossrefPubMedGoogle Scholar
  • 86 Arlt W, Lang K, Sitch AJ. et al. Steroid metabolome analysis reveals prevalent glucocorticoid excess in primary aldosteronism. J Clin Invest Insight 2017; 2: e93136
    PubMedGoogle Scholar
  • 87 Gerards J, Heinrich DA, Adolf C. et al. Impaired glucose metabolism in primary aldosteronism is associated with cortisol cosecretion. J Clin Endocrinol Metab 2019; 104: 3192-3202
    CrossrefPubMedGoogle Scholar
  • 88 Nakajima Y, Yamada M, Taguchi R. et al Cardiovascular complications of patients with aldosteronism associated with autonomous cortisol secretion. J Clin Endocrinol Metab 2011; 96: 2512-2518
    CrossrefPubMedGoogle Scholar