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(Circulation. 2000;102:203.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Renal Function, Neurohormonal Activation, and Survival in Patients With Chronic Heart Failure
From the Department of Clinical Pharmacology, State University Groningen, The Netherlands (H.L.H, D.d.Z.); the Department of Intensive Care, University Hospital of Free University, Amsterdam, The Netherlands (A.R.J.G.); the Department of Cardiology/Thoraxcenter, University Hospital Groningen, The Netherlands (P.J.d.K, D.J.v.V.); COEUR/Department of Internal Medicine, University Hospital Dijkzigt, Rotterdam, The Netherlands (F.B.); Nottingham Clinical Trial Data Centre, Nottingham, United Kingdom (A.C.); and Department of Cardiovascular Medicine, Queen’s Medical Centre, Nottingham, United Kingdom (J.R.H.).
Correspondence to Dr D.J. van Veldhuisen, Department of Cardiology/Thoraxcenter, University Hospital Groningen, Hanzeplein 1, PO Box 30.001, 9700 RB Groningen, The Netherlands. E-mail d.j.van.veldhuisen{at}thorax.azg.nl
Background—Because renal function is affected by chronic heart failure (CHF) and it relates to both cardiovascular and hemodynamic properties, it should have additional prognostic value. We studied whether renal function is a predictor for mortality in advanced CHF, and we assessed its relative contribution compared with other established risk factors. In addition, we studied the relation between renal function and neurohormonal activation.
Methods and Results—The study population consisted of 1906 patients with CHF who were enrolled in a recent survival trial (Second Prospective Randomized study of Ibopamine on Mortality and Efficacy). In a subgroup of 372 patients, plasma neurohormones were determined. The baseline glomerular filtration rate (GFRc) was calculated using the Cockroft Gault equation. GFRc was the most powerful predictor of mortality; it was followed by New York Heart Association functional class and the use of angiotensin-converting enzyme inhibitors. Patients in the lowest quartile of GFRc values (<44 mL/min) had almost 3 times the risk of mortality (relative risk, 2.85; P<0.001) of patients in the highest quartile (>76 mL/min). Impaired left ventricular ejection fraction (LVEF) was only modestly predictive (P=0.053). GFRc was inversely related with N-terminal atrial natriuretic peptide (ANP; r=-0.53) and, to a lesser extent, with ANP itself (r=-0.35; both P<0.001).
Conclusions—Impaired renal function (GFRc) is a stronger predictor of mortality than impaired cardiac function (LVEF and New York Heart Association class) in advanced CHF, and it is associated with increased levels of N-terminal ANP. Moreover, impaired renal function was not related to LVEF, which suggests that factors other than reduced cardiac output are causally involved.
Key Words: heart failure • prognosis • kidney • hormones
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 J. T. Heywood, W. Elatre, R. G. Pai, S. Fabbri, and B. Huiskes Simple Clinical Criteria to Determine the Prognosis of Heart Failure Journal of Cardiovascular Pharmacology and Therapeutics, July 1, 2005; 10(3): 173 - 180. [Abstract] [PDF]
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A. Luchner, C. Hengstenberg, H. Lowel, G. A.J. Riegger, H. Schunkert, and S. Holmer Effect of Compensated Renal Dysfunction on Approved Heart Failure Markers: Direct Comparison of Brain Natriuretic Peptide (BNP) and N-Terminal Pro-BNP Hypertension, July 1, 2005; 46(1): 118 - 123. [Abstract] [Full Text] [PDF]
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R. Vanholder, Z. Massy, A. Argiles, G. Spasovski, F. Verbeke, N. Lameire, and for the European Uremic Toxin Work Group (EUTox) Chronic kidney disease as cause of cardiovascular morbidity and mortality Nephrol. Dial. Transplant., June 1, 2005; 20(6): 1048 - 1056. [Abstract] [Full Text] [PDF]
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M. E. Ochiai, A. C.P. Barretto, M. T. Oliveira Jr., R. T. Munhoz, P. C. Morgado, and J. A.F. Ramires Uric acid renal excretion and renal insufficiency in decompensated severe heart failure Eur J Heart Fail, June 1, 2005; 7(4): 468 - 474. [Abstract] [Full Text] [PDF]
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M. Petersson, P. Friberg, G. Eisenhofer, G. Lambert, and B. Rundqvist Long-term outcome in relation to renal sympathetic activity in patients with chronic heart failure Eur. Heart J., May 1, 2005; 26(9): 906 - 913. [Abstract] [Full Text] [PDF]
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J. D. Sackner-Bernstein, H. A. Skopicki, and K. D. Aaronson Risk of Worsening Renal Function With Nesiritide in Patients With Acutely Decompensated Heart Failure Circulation, March 29, 2005; 111(12): 1487 - 1491. [Abstract] [Full Text] [PDF]
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G. L. Smith, M. G. Shlipak, E. P. Havranek, F. A. Masoudi, W. M. McClellan, J. M. Foody, S. S. Rathore, and H. M. Krumholz Race and Renal Impairment in Heart Failure: Mortality in Blacks Versus Whites Circulation, March 15, 2005; 111(10): 1270 - 1277. [Abstract] [Full Text] [PDF]
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E. M. Stuveling, S. J. L. Bakker, H. L. Hillege, P. E. de Jong, R. O. B. Gans, and D. de Zeeuw Biochemical risk markers: a novel area for better prediction of renal risk? Nephrol. Dial. Transplant., March 1, 2005; 20(3): 497 - 508. [Full Text] [PDF]
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Endorsed by the European Society of Intensive Care, Authors/Task Force Members, M. S. Nieminen, M. Bohm, M. R. Cowie, H. Drexler, G. S. Filippatos, G. Jondeau, Y. Hasin, J. Lopez-Sendon, et al. Executive summary of the guidelines on the diagnosis and treatment of acute heart failure: The Task Force on Acute Heart Failure of the European Society of Cardiology Eur. Heart J., February 2, 2005; 26(4): 384 - 416. [Full Text] [PDF]
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 R. M.A. van de Wal, B. L. van Brussel, A. A. Voors, T. D.J. Smilde, J. C. Kelder, H. A. van Swieten, W. H. van Gilst, D. J. van Veldhuisen, and H.W. T. Plokker Mild preoperative renal dysfunction as a predictor of long-term clinical outcome after coronary bypass surgery J. Thorac. Cardiovasc. Surg., February 1, 2005; 129(2): 330 - 335. [Abstract] [Full Text] [PDF]
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B. G. Loef, A. H. Epema, T. D. Smilde, R. H. Henning, T. Ebels, G. Navis, and C. A. Stegeman Immediate Postoperative Renal Function Deterioration in Cardiac Surgical Patients Predicts In-Hospital Mortality and Long-Term Survival J. Am. Soc. Nephrol., January 1, 2005; 16(1): 195 - 200. [Abstract] [Full Text] [PDF]
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M. Rivera, R. Talens-Visconti, R. Sirera, V. Bertomeu, A. Salvador, R. Cortes, F. G. de Burgos, V. Climent, R. Paya, L. Martinez-Dolz, et al. Soluble TNF-{alpha} and interleukin-6 receptors in the urine of heart failure patients. Their clinical value and relationship with plasma levels Eur J Heart Fail, December 1, 2004; 6(7): 877 - 882. [Abstract] [Full Text] [PDF]
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R. P.E. van Dokkum, W. B.A. Eijkelkamp, A. C.A. Kluppel, R. H. Henning, H. van Goor, M. Citgez, W. A.K.M. Windt, D. J. van Veldhuisen, P. A. de Graeff, and D. de Zeeuw Myocardial Infarction Enhances Progressive Renal Damage in an Experimental Model for Cardio-Renal Interaction J. Am. Soc. Nephrol., December 1, 2004; 15(12): 3103 - 3110. [Abstract] [Full Text] [PDF]
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J. Ezekowitz, F. A. McAlister, K. H. Humphries, C. M. Norris, M. Tonelli, W. A. Ghali, M. L. Knudtson, and APPROACH Investigators The association among renal insufficiency, pharmacotherapy, and outcomes in 6,427 patients with heart failure and coronary artery disease J. Am. Coll. Cardiol., October 19, 2004; 44(8): 1587 - 1592. [Abstract] [Full Text] [PDF]
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K. Bibbins-Domingo, F. Lin, E. Vittinghoff, E. Barrett-Connor, D. Grady, and M. G. Shlipak Renal insufficiency as an independent predictor of mortality among women with heart failure J. Am. Coll. Cardiol., October 19, 2004; 44(8): 1593 - 1600. [Abstract] [Full Text] [PDF]
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M. G. Shlipak and B. M. Massie The Clinical Challenge of Cardiorenal Syndrome Circulation, September 21, 2004; 110(12): 1514 - 1517. [Full Text] [PDF]
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G.M. Felker, K. F. Adams Jr, W. A. Gattis, and C. M. O'Connor Anemia as a risk factor and therapeutic target in heart failure J. Am. Coll. Cardiol., September 1, 2004; 44(5): 959 - 966. [Abstract] [Full Text] [PDF]
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M. G. Shlipak, G. L. Smith, S. S. Rathore, B. M. Massie, and H. M. Krumholz Renal Function, Digoxin Therapy, and Heart Failure Outcomes: Evidence from the Digoxin Intervention Group Trial J. Am. Soc. Nephrol., August 1, 2004; 15(8): 2195 - 2203. [Abstract] [Full Text] [PDF]
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P. van der Meer, A. A. Voors, E. Lipsic, T. D. J. Smilde, W. H. van Gilst, and D. J. van Veldhuisen Prognostic value of plasma erythropoietin on mortality in patients with chronic heart failure J. Am. Coll. Cardiol., July 7, 2004; 44(1): 63 - 67. [Abstract] [Full Text] [PDF]
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A. Cataliotti, G. Boerrigter, L. C. Costello-Boerrigter, J. A. Schirger, T. Tsuruda, D. M. Heublein, H. H. Chen, L. S. Malatino, and J. C. Burnett Jr Brain Natriuretic Peptide Enhances Renal Actions of Furosemide and Suppresses Furosemide-Induced Aldosterone Activation in Experimental Heart Failure Circulation, April 6, 2004; 109(13): 1680 - 1685. [Abstract] [Full Text] [PDF]
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F. A. McAlister, J. Ezekowitz, M. Tonelli, and P. W. Armstrong Renal Insufficiency and Heart Failure: Prognostic and Therapeutic Implications From a Prospective Cohort Study Circulation, March 2, 2004; 109(8): 1004 - 1009. [Abstract] [Full Text] [PDF]
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E. Ritz and W. M. McClellan Overview: Increased Cardiovascular Risk in Patients with Minor Renal Dysfunction: An Emerging Issue with Far-Reaching Consequences J. Am. Soc. Nephrol., March 1, 2004; 15(3): 513 - 516. [Abstract] [Full Text] [PDF]
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T. Pinkau, K. F. Hilgers, R. Veelken, and J. F. E. Mann How Does Minor Renal Dysfunction Influence Cardiovascular Risk and the Management of Cardiovascular Disease? J. Am. Soc. Nephrol., March 1, 2004; 15(3): 517 - 523. [Abstract] [Full Text] [PDF]
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 M. Kyuma, T. Nakata, A. Hashimoto, K. Nagao, H. Sasao, T. Takahashi, K. Tsuchihashi, and K. Shimamoto Incremental Prognostic Implications of Brain Natriuretic Peptide, Cardiac Sympathetic Nerve Innervation, and Noncardiac Disorders in Patients with Heart Failure J. Nucl. Med., February 1, 2004; 45(2): 155 - 163. [Abstract] [Full Text] [PDF]
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