Skip to main content

Advertisement

SpringerLink
Log in

The predictability of renin–angiotensin–aldosterone system factors for clinical outcome in patients with acute decompensated heart failure

  • Original Article
  • Published:
Heart and Vessels Aims and scope Submit manuscript

Abstract

Although counter-regulation between B-type natriuretic peptide (BNP) levels and renin–angiotensin–aldosterone system (RAAS) activation in heart failure (HF) has been suggested, whether the regulation is preserved in acute decompensated heart failure (ADHF) patients remains unclear. This study aimed to determine: (1) the relationship between RAAS activation and clinical outcomes in ADHF patients, and (2) the relationships between plasma BNP levels and degrees of activation in RAAS factors. This study included ADHF patients (n = 103, NYHA3-4, plasma BNP > 200 pg/ml). We studied the predictability of RAAS factors for cardiovascular events and the relationships between plasma BNP levels and the degrees of activation in RAAS factors, which were evaluated by plasma renin activity (PRA) and aldosterone concentration (PAC). PRA was a strong predictor of cardiovascular (CV) events over 1 year, even after accounting for plasma BNP levels (hazard ratio (HR): 1.04, CI [1.02–1.06], p < 0.01) and medication such as RAAS blockers (HR: 1.03, CI [1.01–1.05], p < 0.01), whereas PAC was borderline-significant (univariate analysis, p = 0.06). Cut-off value of PRA (5.3 ng/ml/h) was determined by AUC curve. Of the enrolled patients, higher PRA was found in 40 % of them. Although no correlation between the plasma BNP levels and PRA was found (p = 0.36), after adjusting for hemodynamic parameters, eGFR and medication, a correlation was found between them (p = 0.01). Elevated RAAS factors were found in a substantial number of ADHF patients with high plasma BNP levels in the association with hemodynamic state, which predicts poor clinical outcomes. The measurements of RAAS factors help to stratify ADHF patients at risk for further CV events.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Wilson JR, Schwartz JS, Sutton MS, Ferraro N, Horowitz LN, Reichek N, Josephson ME (1983) Prognosis in severe heart failure: relation to hemodynamic measurements and ventricular ectopic activity. J Am Coll Cardiol 2:403–410

    Article  CAS  PubMed  Google Scholar 

  2. Ishii S, Inomata T, Ikeda Y, Nabeta T, Iwamoto M, Watanabe I, Naruke T, Shinagawa H, Koitabashi T, Nishii M, Takeuchi I, Izumi T (2014) Clinical significance of heart rate during acute decompensated heart failure to predict left ventricular reverse remodeling and prognosis in response to therapies in nonischemic dilated cardiomyopathy. Heart Vessels 29:88–96

    Article  PubMed  Google Scholar 

  3. Gheorghiade M, Pang PS (2009) Acute heart failure syndromes. J Am Coll Cardiol 53:557–573

    Article  PubMed  Google Scholar 

  4. Swedberg K, Eneroth P, Kjekshus J, Wilhelmsen L (1990) Hormones regulating cardiovascular function in patients with severe congestive heart failure and their relation to mortality. Consensus trial study group. Circulation 82:1730–1736

    CAS  Google Scholar 

  5. Schrier RW, Abraham WT (1999) Hormones and hemodynamics in heart failure. N Engl J Med 341:577–585

    Article  CAS  PubMed  Google Scholar 

  6. Cohn JN (2010) Role of the renin-angiotensin system in cardiovascular disease. Cardiovasc Drugs Ther 24:341–344

    Article  PubMed  Google Scholar 

  7. Beygui F, Collet JP, Benoliel JJ, Vignolles N, Dumaine R, Barthelemy O, Montalescot G (2006) High plasma aldosterone levels on admission are associated with death in patients presenting with acute st-elevation myocardial infarction. Circulation 114:2604–2610

    Article  CAS  PubMed  Google Scholar 

  8. Tomaschitz A, Pilz S, Ritz E, Morganti A, Grammer T, Amrein K, Boehm BO, Marz W (2011) Associations of plasma renin with 10-year cardiovascular mortality, sudden cardiac death, and death due to heart failure. Eur Heart J 32:2642–2649

    Article  CAS  PubMed  Google Scholar 

  9. Tomaschitz A, Pilz S, Ritz E, Grammer T, Drechsler C, Boehm BO, Marz W (2011) 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 57:403–414

    Article  CAS  PubMed  Google Scholar 

  10. Nishiyama K, Tsutamoto T, Kawahara C, Yamaji M, Sakai H, Yamamoto T, Fujii M, Horie M (2011) Relationship between biological variation in b-type natriuretic peptide and plasma renin concentration in stable outpatients with dilated cardiomyopathy. Circ J 75:1897–1904

    Article  CAS  PubMed  Google Scholar 

  11. Nishikimi T, Maeda N, Matsuoka H (2006) The role of natriuretic peptides in cardioprotection. Cardiovasc Res 69:318–328

    Article  CAS  PubMed  Google Scholar 

  12. Hobbs RE, Mills RM (2008) Endogenous b-type natriuretic peptide: a limb of the regulatory response to acutely decompensated heart failure. Clin Cardiol 31:407–412

    Article  PubMed  Google Scholar 

  13. Latini R, Masson S, Anand I, Salio M, Hester A, Judd D, Barlera S, Maggioni AP, Tognoni G, Cohn JN (2004) The comparative prognostic value of plasma neurohormones at baseline in patients with heart failure enrolled in val-heft. Eur Heart J 25:292–299

    Article  CAS  PubMed  Google Scholar 

  14. Anand IS, Fisher LD, Chiang YT, Latini R, Masson S, Maggioni AP, Glazer RD, Tognoni G, Cohn JN (2003) Changes in brain natriuretic peptide and norepinephrine over time and mortality and morbidity in the valsartan heart failure trial (val-heft). Circulation 107:1278–1283

    Article  CAS  PubMed  Google Scholar 

  15. Poletti R, Vergaro G, Zyw L, Prontera C, Passino C, Emdin M (2013) Prognostic value of plasma renin activity in heart failure patients with chronic kidney disease. Int J Cardiol 167:711–715

    Article  PubMed  Google Scholar 

  16. Tsutamoto T, Sakai H, Tanaka T, Fujii M, Yamamoto T, Wada A, Ohnishi M, Horie M (2007) Comparison of active renin concentration and plasma renin activity as a prognostic predictor in patients with heart failure. Circ J 71:915–921

    Article  CAS  PubMed  Google Scholar 

  17. de Boer RA, Schroten NF, Bakker SJ, Mahmud H, Szymanski MK, van der Harst P, Gansevoort RT, van Veldhuisen DJ, van Gilst WH, Hillege HL (2012) Plasma renin and outcome in the community: data from prevend. Eur Heart J 33:2351–2359

    Article  PubMed  Google Scholar 

  18. McCullough PA, Duc P, Omland T, McCord J, Nowak RM, Hollander JE, Herrmann HC, Steg PG, Westheim A, Knudsen CW, Storrow AB, Abraham WT, Lamba S, Wu AH, Perez A, Clopton P, Krishnaswamy P, Kazanegra R, Maisel AS (2003) B-type natriuretic peptide and renal function in the diagnosis of heart failure: an analysis from the breathing not properly multinational study. Am J Kidney Dis 41:571–579

    Article  CAS  PubMed  Google Scholar 

  19. Li J, Wang L (2006) B-type natriuretic peptide levels in patients with paroxysmal lone atrial fibrillation. Heart Vessels 21:137–140

    Article  PubMed  Google Scholar 

  20. Takahama H, Yokoyama H, Kada A, Sekiguchi K, Fujino M, Funada A, Amaki M, Hasegawa T, Asakura M, Kanzaki H, Anzai T, Kitakaze M (2013) Extent of heart rate reduction during hospitalization using beta-blockers, not the achieved heart rate itself at discharge, predicts the clinical outcome in patients with acute heart failure syndromes. J Cardiol 61:58–64

    Article  PubMed  Google Scholar 

  21. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, Solomon SD, Spencer KT, Sutton MS, Stewart WJ (2005) 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 18:1440–1463

    Article  PubMed  Google Scholar 

  22. Teichholz LE, Kreulen T, Herman MV, Gorlin R (1976) Problems in echocardiographic volume determinations: echocardiographic–angiographic correlations in the presence of absence of asynergy. Am J Cardiol 37:7–11

    Article  CAS  PubMed  Google Scholar 

  23. Nakabo A, Goda A, Masaki M, Otsuka M, Yoshida C, Eguchi A, Hirotani S, Lee-Kawabata M, Tsujino T, Masuyama T (2014) The impairment of the parasympathetic modulation is involved in the age-related change in mitral e/a ratio. Heart Vessels 29:343–353

    Article  PubMed  Google Scholar 

  24. Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, Yokoyama H, Hishida A (2009) Revised equations for estimated gfr from serum creatinine in Japan. Am J Kidney Dis 53:982–992

    Article  CAS  PubMed  Google Scholar 

  25. Ommen SR, Nishimura RA, Appleton CP, Miller FA, Oh JK, Redfield MM, Tajik AJ (2000) Clinical utility of doppler echocardiography and tissue doppler imaging in the estimation of left ventricular filling pressures: a comparative simultaneous doppler-catheterization study. Circulation 102:1788–1794

    Article  CAS  PubMed  Google Scholar 

  26. Masson S, Solomon S, Angelici L, Latini R, Anand IS, Prescott M, Maggioni AP, Tognoni G, Cohn JN (2010) Elevated plasma renin activity predicts adverse outcome in chronic heart failure, independently of pharmacologic therapy: data from the valsartan heart failure trial (val-heft). J Card Fail 16:964–970

    Article  CAS  PubMed  Google Scholar 

  27. Johnson W, Omland T, Hall C, Lucas C, Myking OL, Collins C, Pfeffer M, Rouleau JL, Stevenson LW (2002) Neurohormonal activation rapidly decreases after intravenous therapy with diuretics and vasodilators for class iv heart failure. J Am Coll Cardiol 39:1623–1629

    Article  CAS  PubMed  Google Scholar 

  28. Dzau V (2005) The cardiovascular continuum and renin–angiotensin–aldosterone system blockade. J Hypertens Suppl 23:S9–S17

    Article  CAS  PubMed  Google Scholar 

  29. Schroten NF, Gaillard CA, van Veldhuisen DJ, Szymanski MK, Hillege HL, de Boer RA (2012) New roles for renin and prorenin in heart failure and cardiorenal crosstalk. Heart Fail Rev 17:191–201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Rademaker MT, Yandle TG, Ellmers LJ, Charles CJ, Nicholls MG, Richards AM (2012) Hemodynamic, hormonal, and renal effects of (pro)renin receptor blockade in experimental heart failure. Circ Heart Fail. 5:645–652

    Article  CAS  PubMed  Google Scholar 

  31. Melnyk RA, Tam J, Boie Y, Kennedy BP, Percival MD (2009) Renin and prorenin activate pathways implicated in organ damage in human mesangial cells independent of angiotensin ii production. Am J Nephrol 30:232–243

    Article  CAS  PubMed  Google Scholar 

  32. Weir RA, Tsorlalis IK, Steedman T, Dargie HJ, Fraser R, McMurray JJ, Connell JM (2011) Aldosterone and cortisol predict medium-term left ventricular remodelling following myocardial infarction. Eur J Heart Fail 13:1305–1313

    Article  CAS  PubMed  Google Scholar 

  33. Tomaschitz A, Ritz E, Pieske B, Fahrleitner-Pammer A, Kienreich K, Horina JH, Drechsler C, Marz W, Ofner M, Pieber TR, Pilz S (2012) Aldosterone and parathyroid hormone: a precarious couple for cardiovascular disease. Cardiovasc Res 94:10–19

    Article  CAS  PubMed  Google Scholar 

  34. Ferrario CM, Strawn WB (2006) Role of the renin–angiotensin–aldosterone system and proinflammatory mediators in cardiovascular disease. Am J Cardiol 98:121–128

    Article  CAS  PubMed  Google Scholar 

  35. Vergaro G, Emdin M, Iervasi A, Zyw L, Gabutti A, Poletti R, Mammini C, Giannoni A, Fontana M, Passino C (2011) Prognostic value of plasma renin activity in heart failure. Am J Cardiol 108:246–251

    Article  CAS  PubMed  Google Scholar 

  36. Tomaschitz A, Pilz S, Ritz E, Meinitzer A, Boehm BO, Marz W (2010) Plasma aldosterone levels are associated with increased cardiovascular mortality: the ludwigshafen risk and cardiovascular health (luric) study. Eur Heart J 31:1237–1247

    Article  CAS  PubMed  Google Scholar 

  37. Tomaschitz A, Pilz S, Pieske B, Ritz E, Marz W, Meinitzer A, Dobnig H, Amrein K, Kienreich K, Verheyen N, Kraigher-Krainer E, Drechsler C, Colantonio C, Wagner D, Fahrleitner-Pammer A (2013) Circulating aldosterone and mortality in female nursing home residents. Exp Gerontol 48:313–318

    Article  CAS  PubMed  Google Scholar 

  38. Fonarow GC, Adams KF Jr, Abraham WT, Yancy CW, Boscardin WJ (2005) Risk stratification for in-hospital mortality in acutely decompensated heart failure: classification and regression tree analysis. JAMA 293:572–580

    Article  CAS  PubMed  Google Scholar 

  39. Miura M, Sakata Y, Nochioka K, Takahashi J, Takada T, Miyata S, Hiramoto T, Inoue K, Tamaki K, Shiba N, Shimokawa H (2013) Prognostic impact of blood urea nitrogen changes during hospitalization in patients with acute heart failure syndrome. Circ J 77:1221–1228

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

We thank Akiko Kada for her helpful advice regarding the statistical analyses. Funding Japan Cardiovascular Research Foundation (grant to H.T.)

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, 565-8565, Japan

    Yasuki Nakada, Hiroyuki Takahama, Hideaki Kanzaki, Yasuo Sugano, Takuya Hasegawa, Takahiro Ohara, Makoto Amaki, Akira Funada, Akemi Yoshida, Satoshi Yasuda, Hisao Ogawa & Toshihisa Anzai

  2. First Department of Internal Medicine, Nara Medical University, Kashihara, Nara, 634-0813, Japan

    Yasuki Nakada

Authors
  1. Yasuki Nakada
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hiroyuki Takahama
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hideaki Kanzaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yasuo Sugano
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takuya Hasegawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Takahiro Ohara
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Makoto Amaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Akira Funada
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Akemi Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Satoshi Yasuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Hisao Ogawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Toshihisa Anzai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hiroyuki Takahama.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nakada, Y., Takahama, H., Kanzaki, H. et al. The predictability of renin–angiotensin–aldosterone system factors for clinical outcome in patients with acute decompensated heart failure. Heart Vessels 31, 925–931 (2016). https://doi.org/10.1007/s00380-015-0688-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00380-015-0688-7

Keywords

Search

Navigation