Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Prospective appraisal of the prevalence of primary aldosteronism in hypertensive patients presenting with atrial flutter or fibrillation (PAPPHY Study): rationale and study design

Journal of Human Hypertension volume 27, pages 158–163 (2013)Cite this article

Subjects

Abstract

Primary aldosteronism (PA) is the most common endocrine form of hypertension and may carry an increased risk of atrial flutter or fibrillation (AFF). The primary goal of this multicentre cohort study is thus to prospectively establish the prevalence of PA in consecutive hypertensive patients referred for lone (non-valvular), paroxysmal or permanent AFF. Secondary objectives are to determine: (1) the predictors of AFF in patients with PA; (2) the rate of AFF recurrence at follow-up after specific treatment in the patients with PA; (3) the effect of AFF that can increase atrial natriuretic peptide via the atrial stretch and thereby blunt aldosterone secretion, on the aldosterone-to-renin ratio (ARR), and thus the case detection of PA; (4) the diagnostic accuracy of ARR based on plasma renin activity or on the measurement of active renin (DRA) for diagnosing PA in AFF patients. Case detection and subtyping of PA will be performed according to established criteria, including the ‘four corners criteria’ for diagnosing aldosterone-producing adenoma. Pharmacologic or direct current cardioversion will be undertaken whenever indicated following current guidelines. The hormonal values and ARR will be compared within patient between AFF and sinus rhythm. Organ damage, cardiovascular events and recurrence of AFF will also be assessed during follow-up in patients with PA.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Rossi GP, Bernini G, Caliumi C, Desideri G, Fabris B, Ferri C et al. A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients. J Am Coll Cardiol 2006; 48: 2293–2300.

    Article  CAS  PubMed  Google Scholar 

  2. Beevers DG, Brown JJ, Ferriss JB, Fraser R, Lever AF, Robertson JI et al. Renal abnormalities and vascular complications in primary hyperaldosteronism. Evidence on tertiary hyperaldosteronism. Q J Med 1976; 45: 401–410.

    CAS  PubMed  Google Scholar 

  3. Rossi G, Boscaro M, Ronconi V, Funder JW . Aldosterone as a cardiovascular risk factor. Trends Endocrinol Metab 2005; 16: 104–107.

    Article  CAS  PubMed  Google Scholar 

  4. 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: 1243–1248.

    Article  CAS  PubMed  Google Scholar 

  5. Porodko M, Auer J, Eber B . Conn's syndrome and atrial fibrillation. Lancet 2001; 357: 1293–1294.

    Article  CAS  PubMed  Google Scholar 

  6. Watson T, Karthikeyan VJ, Lip GY, Beevers DG . Atrial fibrillation in primary aldosteronism. J Renin Angiotensin Aldosterone Syst 2009; 10: 190–194.

    Article  CAS  PubMed  Google Scholar 

  7. Muiesan ML, Salvetti M, Monteduro C, Donato F, Rizzoni D, Agabiti-Rosei E . Various ways of calculating echocardiographic left ventricular mass and their relative prognostic values. J Hypertens 1998; 16: 1201–1206.

    Article  CAS  PubMed  Google Scholar 

  8. Vaziri SM, Larson MG, Lauer MS, Benjamin EJ, Levy D . Influence of blood pressure on left atrial size. The Framingham Heart Study. Hypertension 1995; 25: 1155–1160.

    Article  CAS  PubMed  Google Scholar 

  9. Rossi GP, Sacchetto A, Pavan E, Palatini P, Graniero GR, Canali C et al. Remodeling of the left ventricle in primary aldosteronism due to Conn's adenoma. Circulation 1997; 95: 1471–1478.

    Article  CAS  PubMed  Google Scholar 

  10. Sun Y, Weber KT . Cardiac remodelling by fibrous tissue: role of local factors and circulating hormones. Ann Med 1998; 30 (Suppl 1): 3–8.

    CAS  PubMed  Google Scholar 

  11. Ramires FJ, Sun Y, Weber KT . Myocardial fibrosis associated with aldosterone or angiotensin II administration: attenuation by calcium channel blockade. J Mol Cell Cardiol 1998; 30: 475–483.

    Article  CAS  PubMed  Google Scholar 

  12. Rossi GP, Di Bello V, Ganzaroli C, Sacchetto A, Cesari M, Bertini A et al. Excess aldosterone is associated with alterations of myocardial texture in primary aldosteronism. Hypertension 2002; 40: 23–27.

    Article  CAS  PubMed  Google Scholar 

  13. Franklin SS, Wachtell K, Papademetriou V, Olsen MH, Devereux RB, Fyhrquist F et al. Cardiovascular morbidity and mortality in hypertensive patients with lower versus higher risk: a LIFE substudy. Hypertension 2005; 46: 492–499.

    Article  CAS  PubMed  Google Scholar 

  14. Dahlof B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002; 359: 995–1003.

    Article  CAS  PubMed  Google Scholar 

  15. Schmieder RE, Kjeldsen SE, Julius S, McInnes GT, Zanchetti A, Hua TA et al. Reduced incidence of new-onset atrial fibrillation with angiotensin II receptor blockade: the VALUE trial. J Hypertens 2008; 26: 403–411.

    Article  CAS  PubMed  Google Scholar 

  16. Healey JS, Baranchuk A, Crystal E, Morillo CA, Garfinkle M, Yusuf S et al. Prevention of atrial fibrillation with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: a meta-analysis. J Am Coll Cardiol 2005; 45: 1832–1839.

    Article  CAS  PubMed  Google Scholar 

  17. Schneider MP, Hua TA, Bohm M, Wachtell K, Kjeldsen SE, Schmieder RE . Prevention of atrial fibrillation by Renin-Angiotensin system inhibition a meta-analysis. J Am Coll Cardiol 2010; 55: 2299–2307.

    Article  PubMed  Google Scholar 

  18. Rossi GP . Cardiac consequences of aldosterone excess in human hypertension. Am J Hypertens 2006; 19: 10–12.

    Article  CAS  PubMed  Google Scholar 

  19. Thrall G, Lane D, Carroll D, Lip GY . Quality of life in patients with atrial fibrillation: a systematic review. Am J Med. 2006; 119: 448.e1–448.e19.

    Article  Google Scholar 

  20. Sukor N, Kogovsek C, Gordon RD, Robson D, Stowasser M . Improved quality of life, blood pressure, and biochemical status following laparoscopic adrenalectomy for unilateral primary aldosteronism. J Clin Endocrinol Metab 2010; 95: 1360–1364.

    Article  CAS  PubMed  Google Scholar 

  21. European Heart Rhythm Association; European Association for Cardio-Thoracic Surgery, Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, Ernst S et al. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J 2010; 31: 2369–2429.

    Article  Google Scholar 

  22. Alhadramy O, Jeerakathil TJ, Majumdar SR, Najjar E, Choy J, Saqqur M . Prevalence and predictors of paroxysmal atrial fibrillation on Holter monitor in patients with stroke or transient ischemic attack. Stroke 2010; 41: 2596–2600.

    Article  PubMed  Google Scholar 

  23. Huxley RR, Lopez FL, Folsom AR, Agarwal SK, Loehr LR, Soliman EZ et al. Absolute and attributable risks of atrial fibrillation in relation to optimal and borderline risk factors: the Atherosclerosis Risk in Communities (ARIC) study. Circulation 2011; 123: 1501–1508.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Funder JW, Carey RM, Fardella C, Gomez-Sanchez CE, Mantero F, Stowasser M et al. Case detection, diagnosis, and treatment of patients with primary aldosteronism: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2008; 93: 3266–3281.

    Article  CAS  PubMed  Google Scholar 

  25. Rossi GP . Medscape. A comprehensive review of the clinical aspects of primary aldosteronism. Nat Rev Endocrinol 2011; 7: 485–495.

    Article  PubMed  Google Scholar 

  26. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 2005; 18: 1440–1463.

    Article  PubMed  Google Scholar 

  27. Leung DY, Chi C, Allman C, Boyd A, Ng AC, Kadappu KK et al. Prognostic implications of left atrial volume index in patients in sinus rhythm. Am J Cardiol 2010; 105: 1635–1639.

    Article  PubMed  Google Scholar 

  28. Oral H, Pappone C, Chugh A, Good E, Bogun F, Pelosi F et al. Circumferential pulmonary-vein ablation for chronic atrial fibrillation. N Engl J Med 2006; 354: 934–941.

    Article  CAS  PubMed  Google Scholar 

  29. Marchese P, Bursi F, Delle Donne G, Malavasi V, Casali E, Barbieri A et al. Indexed left atrial volume predicts the recurrence of non-valvular atrial fibrillation after successful cardioversion. Eur J Echocardiogr 2011; 12: 214–221.

    Article  PubMed  Google Scholar 

  30. Rossi GP, Pessina AC, Heagerty AM . Primary aldosteronism: an update on screening, diagnosis and treatment. J Hypertens 2008; 26: 613–621.

    Article  CAS  PubMed  Google Scholar 

  31. Rossi GP, Barisa M, Belfiore A, Desideri G, Ferri C, Letizia C et al. The aldosterone-renin ratio based on the plasma renin activity and the direct renin assay for diagnosing aldosterone-producing adenoma. J Hypertens 2010; 28: 1892–1899.

    Article  CAS  PubMed  Google Scholar 

  32. Campbell DJ, Nussberger J, Stowasser M, Danser AH, Morganti A, Frandsen E et al. Activity assays and immunoassays for plasma Renin and prorenin: information provided and precautions necessary for accurate measurement. Clin Chem 2009; 55: 867–877.

    Article  CAS  PubMed  Google Scholar 

  33. Rossi GP, Seccia TM, Palumbo G, Belfiore A, Bernini G, Caridi G et al. Within-patient reproducibility of the aldosterone: renin ratio in primary aldosteronism. Hypertension 2010; 55: 83–89.

    Article  CAS  PubMed  Google Scholar 

  34. Kageyama Y, Suzuki H, Saruta T . Effects of routine heparin therapy on plasma aldosterone concentration. Acta Endocrinol (Copenh) 1991; 124: 267–270.

    Article  CAS  Google Scholar 

  35. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D . A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999; 130: 461–470.

    Article  CAS  PubMed  Google Scholar 

  36. Rossi GP, Belfiore A, Bernini G, Desideri G, Fabris B, Ferri C et al. Prospective evaluation of the saline infusion test for excluding primary aldosteronism due to aldosterone-producing adenoma. J Hypertens 2007; 25: 1433–1442.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine-DIMED, Internal Medicine 4, University of Padua, Padua, Italy

    G P Rossi, T M Seccia, V Gallina, M Pengo, F Ragazzo, P Caielli & A C Pessina

  2. Department of Internal Medicine, University of Brescia, Brescia, Italy

    M L Muiesan & D Rizzoni

  3. Department of Cardiologic, Thoracic and Vascular Sciences, University of Padua, Padua, Italy

    L Leoni

  4. Department of Internal Medicine, University of Bari, Bari, Italy

    A Belfiore

  5. Department of Internal Medicine, University of Pisa, Pisa, Italy

    G Bernini

  6. Department of Internal Medicine, University of Chieti, Chieti, Italy

    F Cipollone

  7. Department of Internal Medicine, University of Palermo, Palermo, Italy

    S Cottone

  8. Department of Internal Medicine, University of L'Aquila, L'Aquila, Italy

    C Ferri

  9. Department of Endocrinology, University of Ancona, Ancona, Italy

    G Giacchetti

  10. Department of Internal Medicine, University of Milan Bicocca, Milan, Italy

    G Grassi & A Morganti

  11. Department of Internal Medicine, University La Sapienza Rome, Rome, Italy

    C Letizia

  12. Department of Endocrinology, University of Turin, Turin, Italy

    M Maccario

  13. Department of Internal Medicine, University of Verona, Verona, Italy

    O Olivieri

  14. Department of Internal Medicine, Legnano Hospital,

    G Palumbo

  15. Department of Internal Medicine, Reggio Emilia Hospital,

    E Rossi

  16. Department of Internal Medicine, University of Udine, Udine, Italy

    L Sechi

  17. Department of Cardiology, University La Sapienza Rome and IRCCS Neuromed, Pozzilli, Italy

    M Volpe

  18. Department of Medicine-DIMED, Endocrinology, University of Padua, Padua, Italy

    F Mantero

  19. Department of Medicine, San Giuseppe Hospital, University of Milan, Milan, Italy

    A Morganti

Authors
  1. G P Rossi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T M Seccia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V Gallina
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M L Muiesan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. L Leoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M Pengo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. F Ragazzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. P Caielli
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. A Belfiore
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. G Bernini
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. F Cipollone
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. S Cottone
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. C Ferri
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. G Giacchetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. G Grassi
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. C Letizia
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. M Maccario
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. O Olivieri
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. G Palumbo
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. D Rizzoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. E Rossi
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. L Sechi
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. M Volpe
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. F Mantero
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. A Morganti
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. A C Pessina
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G P Rossi.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rossi, G., Seccia, T., Gallina, V. et al. Prospective appraisal of the prevalence of primary aldosteronism in hypertensive patients presenting with atrial flutter or fibrillation (PAPPHY Study): rationale and study design. J Hum Hypertens 27, 158–163 (2013). https://doi.org/10.1038/jhh.2012.21

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jhh.2012.21

Keywords

This article is cited by

Search

Advanced search

Quick links