CLINICAL STUDIES
The prognostic implications of renal insufficiency in asymptomatic and symptomatic patients with left ventricular systolic dysfunction
Daniel L. Dries, MD, MPH*,
Derek V. Exner, MD, MPH ,
Michael J. Domanski, MD,
Barry Greenberg, MD and
Lynne W. Stevenson, MD, FACC*
* Division of Cardiology, Brigham and Women’s Hospital, Boston, Massachusetts, USA
Clinical Trials Research Group, Division of Epidemiology and Clinical Applications, National Heart, Lung and Blood Institute, Bethesda, Maryland, USA
Division of Cardiology, University of California at San Diego, San Diego, California, USA
Manuscript received January 28, 1999;
revised manuscript received November 10, 1999,
accepted November 15, 1999.
Reprint requests and correspondence: Dr. Daniel L. Dries, Cardiomyopathy Transplant Fellow, Division of Cardiology, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02115
OBJECTIVES
The present analysis examines the prognostic implications of moderate renal insufficiency in patients with asymptomatic and symptomatic left ventricular systolic dysfunction.
BACKGROUND
Chronic elevations in intracardiac filling pressures may lead to progressive ventricular dilation and heart failure progression. The ability to maintain fluid balance and prevent increased intracardiac filling pressures is critically dependent on the adequacy of renal function.
METHODS
This is a retrospective analysis of the Studies of Left Ventricular Dysfunction (SOLVD) Trials, in which moderate renal insufficiency is defined as a baseline creatinine clearance <60 ml/min, as estimated from the Cockroft-Gault equation.
RESULTS
In the SOLVD Prevention Trial, multivariate analyses demonstrated moderate renal insufficiency to be associated with an increased risk for all-cause mortality (Relative Risk [RR] 1.41; p = 0.001), largely explained by an increased risk for pump-failure death (RR 1.68;p = 0.007) and the combined end point death or hospitalization for heart failure (RR 1.33; p = 0.001). Likewise, in the Treatment Trial, multivariate analyses demonstrated moderate renal insufficiency to be associated with an increased risk for all-cause mortality (RR 1.41;p = 0.001), also largely explained by an increased risk for pump-failure death (RR 1.49; p = 0.007) and the combined end point death or hospitalization for heart failure (RR 1.45; p = 0.001).
CONCLUSIONS
Even moderate degrees of renal insufficiency are independently associated with an increased risk for all-cause mortality in patients with heart failure, largely explained by an increased risk of heart failure progression. These data suggest that, rather than simply being a marker of the severity of underlying disease, the adequacy of renal function may be a primary determinant of compensation in patients with heart failure, and therapy capable of improving renal function may delay disease progression.
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Abbreviations and Acronyms
| | BUN | = blood urea nitrogen | | CI | = confidence interval | | CrCl | = creatinine clearance | | LVEF | = left ventricular ejection fraction | | NYHA | = New York Heart Association | | RR | = relative risk | | SOLVD | = Studies of Left Ventricular Dysfunction |
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|
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29(8):
1029 - 1036.
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|
|
|
|
|
|
|
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51(13):
1268 - 1274.
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|
|
|
|
|
|
|
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Prevalence of chronic kidney disease stages 3-5 among acute medical admissions: another opportunity for screening
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101(2):
91 - 97.
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|
|
|
|
|
|
|
D. Pereg, A. Tirosh, T. Shochat, D. Hasdai, and for the Metabolic, Lifestyle and Nutrition Assessm
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29(2):
198 - 203.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. T. van Domburg, S. E. Hoeks, G. M.J.M. Welten, M. Chonchol, A. Elhendy, and D. Poldermans
Renal Insufficiency and Mortality in Patients with Known or Suspected Coronary Artery Disease
J. Am. Soc. Nephrol.,
January 1, 2008;
19(1):
158 - 163.
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[Full Text]
[PDF]
|
|
|
|
|
|
|
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J. Am. Soc. Nephrol.,
January 1, 2008;
19(1):
141 - 150.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. S. Gardner, K. S. Chong, E. O'Meara, A. Jardine, I. Ford, and T. A. McDonagh
Renal dysfunction, as measured by the modification of diet in renal disease equations, and outcome in patients with advanced heart failure
Eur. Heart J.,
December 2, 2007;
28(24):
3027 - 3033.
[Abstract]
[Full Text]
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|
|
|
|
|
|
|
R. M. Witteles, D. Kao, D. Christopherson, K. Matsuda, R. H. Vagelos, D. Schreiber, and M. B. Fowler
Impact of Nesiritide on Renal Function in Patients With Acute Decompensated Heart Failure and Pre-Existing Renal Dysfunction: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
J. Am. Coll. Cardiol.,
November 6, 2007;
50(19):
1835 - 1840.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Arora, K. Clarke, V. Srinivasan, and A. Gradman
Effect of nesiritide on renal function in patients admitted for decompensated heart failure
QJM,
November 1, 2007;
100(11):
699 - 706.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. O. Phillips, A. Kashani, D. K. Ko, G. Francis, and H. M. Krumholz
Adverse Effects of Combination Angiotensin II Receptor Blockers Plus Angiotensin-Converting Enzyme Inhibitors for Left Ventricular Dysfunction: A Quantitative Review of Data From Randomized Clinical Trials
Arch Intern Med,
October 8, 2007;
167(18):
1930 - 1936.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Verma, N. S. Anavekar, A. Meris, J. J. Thune, J. M. O. Arnold, J. K. Ghali, E. J. Velazquez, J. J.V. McMurray, M. A. Pfeffer, and S. D. Solomon
The Relationship Between Renal Function and Cardiac Structure, Function, and Prognosis After Myocardial Infarction: The VALIANT Echo Study
J. Am. Coll. Cardiol.,
September 25, 2007;
50(13):
1238 - 1245.
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[Full Text]
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|
|
|
|
|
|
|
C. Daly
Is early chronic kidney disease an important risk factor for cardiovascular disease?: A Background Paper prepared for the UK Consensus Conference on Early Chronic Kidney Disease
Nephrol. Dial. Transplant.,
September 1, 2007;
22(suppl_9):
ix19 - ix25.
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. C. Costello-Boerrigter, G. Boerrigter, G. J. Harty, A. Cataliotti, M. M. Redfield, and J. C. Burnett Jr
Mineralocorticoid Escape by the Kidney But Not the Heart in Experimental Asymptomatic Left Ventricular Dysfunction
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September 1, 2007;
50(3):
481 - 488.
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[Full Text]
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|
|
|
|
|
|
|
G. Boerrigter, L. C. Costello-Boerrigter, A. Cataliotti, H. Lapp, J.-P. Stasch, and J. C. Burnett Jr
Targeting Heme-Oxidized Soluble Guanylate Cyclase in Experimental Heart Failure
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May 1, 2007;
49(5):
1128 - 1133.
[Abstract]
[Full Text]
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|
|
|
|
|
|
|
A. Kottgen, S. D. Russell, L. R. Loehr, C. M. Crainiceanu, W. D. Rosamond, P. P. Chang, L. E. Chambless, and J. Coresh
Reduced Kidney Function as a Risk Factor for Incident Heart Failure: The Atherosclerosis Risk in Communities (ARIC) Study
J. Am. Soc. Nephrol.,
April 1, 2007;
18(4):
1307 - 1315.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Redon, F. Morales-Olivas, A. Galgo, M. A. Brito, J. Mediavilla, R. Marin, P. Rodriguez, S. Tranche, J. V. Lozano, C. Filozof, et al.
Urinary Albumin Excretion and Glomerular Filtration Rate across the Spectrum of Glucose Abnormalities in Essential Hypertension
J. Am. Soc. Nephrol.,
December 1, 2006;
17(12_suppl_3):
S236 - S245.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. E. Jie, M. C. Verhaar, M.-J. M. Cramer, K. van der Putten, C. A. J. M. Gaillard, P. A. Doevendans, H. A. Koomans, J. A. Joles, and B. Braam
Erythropoietin and the cardiorenal syndrome: cellular mechanisms on the cardiorenal connectors
Am J Physiol Renal Physiol,
November 1, 2006;
291(5):
F932 - F944.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. R.J. van Kimmenade, J. L. Januzzi Jr, A. L. Baggish, J. G. Lainchbury, A. Bayes-Genis, A. M. Richards, and Y. M. Pinto
Amino-Terminal Pro-Brain Natriuretic Peptide, Renal Function, and Outcomes in Acute Heart Failure: Redefining the Cardiorenal Interaction?
J. Am. Coll. Cardiol.,
October 17, 2006;
48(8):
1621 - 1627.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. D.J. Smilde, D. J. van Veldhuisen, G. Navis, A. A. Voors, and H. L. Hillege
Drawbacks and Prognostic Value of Formulas Estimating Renal Function in Patients With Chronic Heart Failure and Systolic Dysfunction
Circulation,
October 10, 2006;
114(15):
1572 - 1580.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Jose, H. Skali, N. Anavekar, C. Tomson, H. M. Krumholz, J. L. Rouleau, L. Moye, M. A. Pfeffer, S. D. Solomon, and for the SAVE Investigators
Increase in Creatinine and Cardiovascular Risk in Patients with Systolic Dysfunction after Myocardial Infarction
J. Am. Soc. Nephrol.,
October 1, 2006;
17(10):
2886 - 2891.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. S. Hillis, K. J. Zehr, A. W. Williams, H. V. Schaff, T. A. Orzulak, R. C. Daly, C. J. Mullany, R. J. Rodeheffer, and J. K. Oh
Outcome of Patients With Low Ejection Fraction Undergoing Coronary Artery Bypass Grafting: Renal Function and Mortality After 3.8 Years
Circulation,
July 4, 2006;
114(1_suppl):
I-414 - I-419.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Tonelli, N. Wiebe, B. Culleton, A. House, C. Rabbat, M. Fok, F. McAlister, and A. X. Garg
Chronic Kidney Disease and Mortality Risk: A Systematic Review
J. Am. Soc. Nephrol.,
July 1, 2006;
17(7):
2034 - 2047.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. S. Go, J. Yang, L. M. Ackerson, K. Lepper, S. Robbins, B. M. Massie, and M. G. Shlipak
Hemoglobin Level, Chronic Kidney Disease, and the Risks of Death and Hospitalization in Adults With Chronic Heart Failure: The Anemia in Chronic Heart Failure: Outcomes and Resource Utilization (ANCHOR) Study
Circulation,
June 13, 2006;
113(23):
2713 - 2723.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L Grigorian Shamagian, A Varela Roman, J M Garcia-Acuna, P Mazon Ramos, A Virgos Lamela, and J R Gonzalez-Juanatey
Anaemia is associated with higher mortality among patients with heart failure with preserved systolic function
Heart,
June 1, 2006;
92(6):
780 - 784.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Ponikowski
Rationale and design of CIBIS III
Eur. Heart J. Suppl.,
June 1, 2006;
8(suppl_C):
C35 - C42.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-D. Tang and S. D. Katz
Anemia in Chronic Heart Failure: Prevalence, Etiology, Clinical Correlates, and Treatment Options
Circulation,
May 23, 2006;
113(20):
2454 - 2461.
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. L. Smith, M. G. Shlipak, E. P. Havranek, J. M. Foody, F. A. Masoudi, S. S. Rathore, and H. M. Krumholz
Serum urea nitrogen, creatinine, and estimators of renal function: mortality in older patients with cardiovascular disease.
Arch Intern Med,
May 22, 2006;
166(10):
1134 - 1142.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. L. Smith, J. H. Lichtman, M. B. Bracken, M. G. Shlipak, C. O. Phillips, P. DiCapua, and H. M. Krumholz
Renal Impairment and Outcomes in Heart Failure: Systematic Review and Meta-Analysis
J. Am. Coll. Cardiol.,
May 16, 2006;
47(10):
1987 - 1996.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. R. Hemmelgarn, D. A. Southern, K. H. Humphries, B. F. Culleton, M. L. Knudtson, W. A. Ghali, and for the Alberta Provincial Project for Outcomes As
Refined characterization of the association between kidney function and mortality in patients undergoing cardiac catheterization
Eur. Heart J.,
May 2, 2006;
27(10):
1191 - 1197.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Meisinger, A. Doring, H. Lowel, and for the KORA Study Group
Chronic kidney disease and risk of incident myocardial infarction and all-cause and cardiovascular disease mortality in middle-aged men and women from the general population
Eur. Heart J.,
May 2, 2006;
27(10):
1245 - 1250.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. R. Cowie, M. Komajda, T. Murray-Thomas, J. Underwood, B. Ticho, and on behalf of the POSH Investigators
Prevalence and impact of worsening renal function in patients hospitalized with decompensated heart failure: results of the prospective outcomes study in heart failure (POSH)
Eur. Heart J.,
May 2, 2006;
27(10):
1216 - 1222.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Butler, C. Geisberg, R. Howser, P. M. Portner, J. G. Rogers, M. C. Deng, and R. N. Pierson III
Relationship between renal function and left ventricular assist device use.
Ann. Thorac. Surg.,
May 1, 2006;
81(5):
1745 - 1751.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. de Silva, N. P. Nikitin, K. K.A. Witte, A. S. Rigby, K. Goode, S. Bhandari, A. L. Clark, and J. G.F. Cleland
Incidence of renal dysfunction over 6 months in patients with chronic heart failure due to left ventricular systolic dysfunction: contributing factors and relationship to prognosis
Eur. Heart J.,
March 1, 2006;
27(5):
569 - 581.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. E. Gilbert, K. Connelly, D. J. Kelly, C. A. Pollock, and H. Krum
Heart Failure and Nephropathy: Catastrophic and Interrelated Complications of Diabetes
Clin. J. Am. Soc. Nephrol.,
March 1, 2006;
1(2):
193 - 208.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. L. Hillege, D. Nitsch, M. A. Pfeffer, K. Swedberg, J. J.V. McMurray, S. Yusuf, C. B. Granger, E. L. Michelson, J. Ostergren, J. H. Cornel, et al.
Renal Function as a Predictor of Outcome in a Broad Spectrum of Patients With Heart Failure
Circulation,
February 7, 2006;
113(5):
671 - 678.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Maaravi, M. Bursztyn, R. Hammerman-Rozenberg, A. Cohen, and J. Stessman
Moderate renal insufficiency at 70 years predicts mortality
QJM,
February 1, 2006;
99(2):
97 - 102.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. C. Costello-Boerrigter, W. B. Smith, G. Boerrigter, J. Ouyang, C. A. Zimmer, C. Orlandi, and J. C. Burnett Jr.
Vasopressin-2-receptor antagonism augments water excretion without changes in renal hemodynamics or sodium and potassium excretion in human heart failure
Am J Physiol Renal Physiol,
February 1, 2006;
290(2):
F273 - F278.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Lisy and J. C. Burnett Jr
New Cardioprotective Agent K201 Is Natriuretic and Glomerular Filtration Rate Enhancing
Circulation,
January 17, 2006;
113(2):
246 - 251.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. W. Schrier
Role of Diminished Renal Function in Cardiovascular Mortality: Marker or Pathogenetic Factor?
J. Am. Coll. Cardiol.,
January 3, 2006;
47(1):
1 - 8.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
S. Anwaruddin, D. M. Lloyd-Jones, A. Baggish, A. Chen, D. Krauser, R. Tung, C. Chae, and J. L. Januzzi Jr
Renal Function, Congestive Heart Failure, and Amino-Terminal Pro-Brain Natriuretic Peptide Measurement: Results From the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) Study
J. Am. Coll. Cardiol.,
January 3, 2006;
47(1):
91 - 97.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. A. Khan, I. Ma, C. R. Thompson, K. Humphries, D. N. Salem, M. J. Sarnak, and A. Levin
Kidney Function and Mortality among Patients with Left Ventricular Systolic Dysfunction
J. Am. Soc. Nephrol.,
January 1, 2006;
17(1):
244 - 253.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Anwaruddin, D. M. Lloyd-Jones, A. Baggish, A. Chen, D. Krauser, R. Tung, C. Chae, and J. L. Januzzi Jr
Renal Function, Congestive Heart Failure, and Amino-Terminal Pro-Brain Natriuretic Peptide Measurement: Results From the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) Study
J. Am. Coll. Cardiol.,
December 13, 2005;
(2005)
j.jacc.2005.08.051v1.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. C. Burnett Jr
Urocortin: Advancing the Neurohumoral Hypothesis of Heart Failure
Circulation,
December 6, 2005;
112(23):
3544 - 3546.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. de Silva, N. P. Nikitin, S. Bhandari, A. Nicholson, A. L. Clark, and J. G.F. Cleland
Atherosclerotic renovascular disease in chronic heart failure: should we intervene?
Eur. Heart J.,
August 2, 2005;
26(16):
1596 - 1605.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. A. Masoudi, C. P. Gross, Y. Wang, S. S. Rathore, E. P. Havranek, J. M. Foody, and H. M. Krumholz
Adoption of Spironolactone Therapy for Older Patients With Heart Failure and Left Ventricular Systolic Dysfunction in the United States, 1998-2001
Circulation,
July 5, 2005;
112(1):
39 - 47.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. W. Stevenson, A. Nohria, and L. Mielniczuk
Torrent or Torment From the Tubules?: Challenge of the Cardiorenal Connections
J. Am. Coll. Cardiol.,
June 21, 2005;
45(12):
2004 - 2007.
[Full Text]
[PDF]
|
|
|
|
|
|
|
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