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J Am Coll Cardiol, 2001; 38:955-962
© 2001 by the American College of Cardiology Foundation
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CLINICAL STUDY

Reduced kidney function and anemia as risk factors for mortality in patients with left ventricular dysfunction

Amin Al-Ahmad, MD*, William M. Rand, PhD{dagger}, Guruprasad Manjunath, MD{ddagger}, Marvin A. Konstam, MD*, Deeb N. Salem, MD*, Andrew S. Levey, MD{ddagger} and Mark J. Sarnak, MD{ddagger}

* Division of Cardiology, Department of Medicine, New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA
{dagger} Department of Community Health, Tufts University School of Medicine, Boston, Massachusetts, USA
{ddagger} Division of Nephrology, Department of Medicine, New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA

Manuscript received February 23, 2001; revised manuscript received May 21, 2001, accepted June 11, 2001.

Reprint requests and correspondence: Dr. Mark J. Sarnak, New England Medical Center, Box 391, 750 Washington Street, Boston, Massachusetts 02111
msarnak{at}lifespan.org

OBJECTIVES

We sought to evaluate the relationship between the level of kidney function, level of hematocrit and their interaction on all-cause mortality in patients with left ventricular (LV) dysfunction.

BACKGROUND

Anemia and reduced kidney function occur frequently in patients with heart failure. The level of hematocrit and its relationship with renal function have not been evaluated as risk factors for mortality in patients with LV dysfunction.

METHODS

We retrospectively examined the Studies Of LV Dysfunction (SOLVD) database. Glomerular filtration rate (GFR) was predicted using a recently validated formula. Kaplan-Meier survival analyses were used to compare survival times between groups stratified by level of kidney function (predicted GFR) and hematocrit. Cox proportional-hazards regression was used to explore the relationship of survival time to level of kidney function, hematocrit and their interaction.

RESULTS

Lower GFR and hematocrit were associated with a higher prevalence of traditional cardiovascular risk factors. In univariate analysis, reduced kidney function and lower hematocrit, in men and in women, were risk factors for all-cause mortality (p < 0.001 for both). After adjustment for other factors significant in univariate analysis, a 10 ml/min/1.73 m2 lower GFR and a 1% lower hematocrit were associated with a 1.064 (95% CI: 1.033, 1.096) and 1.027 (95% CI: 1.015, 1.038) higher risk for mortality, respectively. At lower GFR and lower hematocrit, the risk was higher (p = 0.022 for the interaction) than that predicted by both factors independently.

CONCLUSIONS

Decreased kidney function and anemia are risk factors for all-cause mortality in patients with LV dysfunction, especially when both are present. These relationships need to be confirmed in additional studies.

Abbreviations and Acronyms
  ACE = angiotensin-converting enzyme
  ESRD = end-stage renal disease
  GFR = glomerular filtration rate
  HF = heart failure
  LV = left ventricle or left ventricular
  MDRD = Modification of Diet in Renal Disease
  NYHA = New York Heart Association
  SOLVD = Studies Of Left Ventricular Dysfunction




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Developed in Collaboration With the American Colle, Endorsed by the Heart Rhythm Society, S. A. Hunt, W. T. Abraham, M. H. Chin, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. Jessup, M. A. Konstam, et al.
ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult--Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure)
J. Am. Coll. Cardiol., September 20, 2005; 46(6): 1116 - 1143.
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 CirculationHome page
S. A. Hunt, W. T. Abraham, M. H. Chin, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. Jessup, M. A. Konstam, D. M. Mancini, K. Michl, et al.
ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult--Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): Developed in Collaboration With the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: Endorsed by the Heart Rhythm Society
Circulation, September 20, 2005; 112(12): 1825 - 1852.
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 ChestHome page
A. Chambellan, E. Chailleux, and T. Similowski
Prognostic Value of the Hematocrit in Patients With Severe COPD Receiving Long-term Oxygen Therapy
Chest, September 1, 2005; 128(3): 1201 - 1208.
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 Nephrol Dial TransplantHome page
P. Gil, S. Justo, and C. Caramelo
Cardio-renal failure: an emerging clinical entity
Nephrol. Dial. Transplant., September 1, 2005; 20(9): 1780 - 1783.
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 J Am Coll CardiolHome page
K. F. Adams Jr, J. H. Patterson, W. A. Gattis, C. M. O'Connor, C. R. Lee, T. A. Schwartz, and M. Gheorghiade
Relationship of Serum Digoxin Concentration to Mortality and Morbidity in Women in the Digitalis Investigation Group Trial: A Retrospective Analysis
J. Am. Coll. Cardiol., August 2, 2005; 46(3): 497 - 504.
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 Arch Intern MedHome page
J. George, S. Patal, D. Wexler, A. Abashidze, H. Shmilovich, T. Barak, D. Sheps, and G. Keren
Circulating Erythropoietin Levels and Prognosis in Patients With Congestive Heart Failure: Comparison With Neurohormonal and Inflammatory Markers
Arch Intern Med, June 13, 2005; 165(11): 1304 - 1309.
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 Nephrol Dial TransplantHome page
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.
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 J. Am. Soc. Nephrol.Home page
D. E. Weiner, H. Tighiouart, P. T. Vlagopoulos, J. L. Griffith, D. N. Salem, A. S. Levey, and M. J. Sarnak
Effects of Anemia and Left Ventricular Hypertrophy on Cardiovascular Disease in Patients with Chronic Kidney Disease
J. Am. Soc. Nephrol., June 1, 2005; 16(6): 1803 - 1810.
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 J Am Coll CardiolHome page
S. Namiuchi, Y. Kagaya, J. Ohta, N. Shiba, M. Sugi, M. Oikawa, H. Kunii, H. Yamao, N. Komatsu, M. Yui, et al.
High Serum Erythropoietin Level Is Associated With Smaller Infarct Size in Patients With Acute Myocardial Infarction Who Undergo Successful Primary Percutaneous Coronary Intervention
J. Am. Coll. Cardiol., May 3, 2005; 45(9): 1406 - 1412.
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 Nephrol Dial TransplantHome page
S. Philipp, H. Ollmann, T. Schink, R. Dietz, F. C. Luft, and R. Willenbrock
The impact of anaemia and kidney function in congestive heart failure and preserved systolic function
Nephrol. Dial. Transplant., May 1, 2005; 20(5): 915 - 919.
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 CirculationHome page
M. S. Sabatine, D. A. Morrow, R. P. Giugliano, P. B.J. Burton, S. A. Murphy, C. H. McCabe, C. M. Gibson, and E. Braunwald
Association of Hemoglobin Levels With Clinical Outcomes in Acute Coronary Syndromes
Circulation, April 26, 2005; 111(16): 2042 - 2049.
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 CirculationHome page
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.
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 J Am Coll CardiolHome page
A. Ishani, E. Weinhandl, Z. Zhao, D. T. Gilbertson, A. J. Collins, S. Yusuf, and C. A. Herzog
Angiotensin-converting enzyme inhibitor as a risk factor for the development of anemia, and the impact of incident anemia on mortality in patients with left ventricular dysfunction
J. Am. Coll. Cardiol., February 1, 2005; 45(3): 391 - 399.
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 J. Am. Soc. Nephrol.Home page
P. Muntner, J. He, B. C. Astor, A. R. Folsom, and J. Coresh
Traditional and Nontraditional Risk Factors Predict Coronary Heart Disease in Chronic Kidney Disease: Results from the Atherosclerosis Risk in Communities Study
J. Am. Soc. Nephrol., February 1, 2005; 16(2): 529 - 538.
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 J Am Coll CardiolHome page
M. G. Shlipak, M. J. Sarnak, R. Katz, L. Fried, S. Seliger, A. Newman, D. Siscovick, and C. Stehman-Breen
Cystatin-C and mortality in elderly persons with heart failure
J. Am. Coll. Cardiol., January 18, 2005; 45(2): 268 - 271.
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 The Annals of PharmacotherapyHome page
K. Caiola and J. W. Cheng
Use of Erythropoietin in Heart Failure Management
Ann. Pharmacother., December 1, 2004; 38(12): 2145 - 2149.
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 J Am Coll CardiolHome page
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.
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 NEJMHome page
N. S. Anavekar, J. J.V. McMurray, E. J. Velazquez, S. D. Solomon, L. Kober, J.-L. Rouleau, H. D. White, R. Nordlander, A. Maggioni, K. Dickstein, et al.
Relation between Renal Dysfunction and Cardiovascular Outcomes after Myocardial Infarction
N. Engl. J. Med., September 23, 2004; 351(13): 1285 - 1295.
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 J Am Coll CardiolHome page
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.
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 HeartHome page
A J S Coats
Anaemia and heart failure
Heart, September 1, 2004; 90(9): 977 - 979.
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 J. Am. Soc. Nephrol.Home page
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.
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 CirculationHome page
I. Anand, J. J.V. McMurray, J. Whitmore, M. Warren, A. Pham, M. A. McCamish, and P. B.J. Burton
Anemia and Its Relationship to Clinical Outcome in Heart Failure
Circulation, July 13, 2004; 110(2): 149 - 154.
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 Biol Res NursHome page
T. R. Wessel, C. B. Arant, and C. J. Pepine
Commentary on "New and Emerging Theories of Cardiovascular Disease"
Biol Res Nurs, July 1, 2004; 6(1): 17 - 20.
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 Eur Heart JHome page
R. Sharma, D. P Francis, B. Pitt, P. A Poole-Wilson, A. J.S Coats, and S. D Anker
Haemoglobin predicts survival in patients with chronic heart failure: a substudy of the ELITE II trial
Eur. Heart J., June 2, 2004; 25(12): 1021 - 1028.
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 J Am Coll CardiolHome page
M. G. Amin, H. Tighiouart, D. E. Weiner, P. C. Stark, J. L. Griffith, B. MacLeod, D. N. Salem, and M. J. Sarnak
Hematocrit and left ventricular mass: the Framingham Heart study
J. Am. Coll. Cardiol., April 7, 2004; 43(7): 1276 - 1282.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
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.
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 JNMHome page
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.
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 Eur Heart JHome page
H. Reinecke, T. Trey, J. Wellmann, J. Heidrich, M. Fobker, T. Wichter, M. Walter, G. Breithardt, and R. M. Schaefer
Haemoglobin-related mortality in patients undergoing percutaneous coronary interventions
Eur. Heart J., December 1, 2003; 24(23): 2142 - 2150.
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 J. Am. Soc. Nephrol.Home page
C. T. Jurkovitz, J. L. Abramson, L. V. Vaccarino, W. S. Weintraub, and W. M. McClellan
Association of High Serum Creatinine and Anemia Increases the Risk of Coronary Events: Results from the Prospective Community-Based Atherosclerosis Risk in Communities (ARIC) Study
J. Am. Soc. Nephrol., November 1, 2003; 14(11): 2919 - 2925.
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 Nephrol Dial TransplantHome page
A. Levin
The advantage of a uniform terminology and staging system for chronic kidney disease (CKD)
Nephrol. Dial. Transplant., August 1, 2003; 18(8): 1446 - 1451.
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 Nephrol Dial TransplantHome page
A. Levin
The advantage of a uniform terminology and staging system for chronic kidney disease (CKD)
Nephrol. Dial. Transplant., August 1, 2003; 18(88): 1446 - 1451.
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 J Am Coll CardiolHome page
J. S. Zebrack, J. L. Anderson, S. Beddhu, B. D. Horne, T. L. Bair, A. Cheung, J. B. Muhlestein, and Intermountain Heart Collaborative Study Group
Do associations with C-Reactive protein and extent of coronary artery disease account for the increased cardiovascular risk of renal insufficiency?
J. Am. Coll. Cardiol., July 2, 2003; 42(1): 57 - 63.
[Abstract] [Full Text] [PDF]


 
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