Renal Function as a Predictor of Outcome in a Broad Spectrum of Patients With Heart Failure
Abstract
Background— Decreased renal function has been found to be an independent risk factor for cardiovascular outcomes in patients with chronic heart failure (CHF) with markedly reduced left ventricular ejection fraction (LVEF). The aim of this analysis was to evaluate the prognostic importance of renal function in a broader spectrum of patients with CHF. Methods and Results— The Candesartan in Heart Failure:Assessment of Reduction in Mortality and Morbidity (CHARM) program consisted of three component trials that enrolled patients with symptomatic CHF, based on use of ACE inhibitors and reduced (≤40%) or preserved LVEF (>40%). Entry baseline creatinine was required to be below 3.0 mg/dL (265 μmol/L). Routine baseline serum creatinine assessments were done in 2680 North American patients. An analysis of the estimated glomerular filtration rate (eGFR), using the Modification of Diet in Renal Disease equation and LVEF on risk of cardiovascular death or hospitalization for heart failure, as well as on all-cause mortality, was conducted on these 2680 patients. The proportion of patients with eGFR <60 mL/min per 1.73 m 2 was 36.0%; 42.6% for CHARM-Alternative, 33.0% for CHARM-Added, and 34.7% for CHARM-Preserved. During the median follow-up of 34.4 months (total 6493 person-years), the primary outcome of cardiovascular death or hospital admission for worsening CHF occurred in 950 of 2680 subjects. Both reduced eGFR and lower LVEF were found to be significant independent predictors of worse outcome after adjustment for major confounding baseline clinical characteristics. The risk for cardiovascular death or hospitalization for worsening CHF as well as the risk for all-cause mortality increased significantly below an eGFR of 60 mL/min per 1.73 m 2 (adjusted hazard ratio, 1.54 for 45 to 60 mL/min per 1.73 m 2 and 1.86 for <45 mL/min per 1.73 m 2 for the primary outcome, both P <0.001, and hazard ratio of 1.50, P =0.006, and 1.91, P =0.001, respectively, for all-cause mortality). The prognostic value of eGFR was not significantly different among the three component trials. There was no significant interaction between renal function, the effect of candesartan, and clinical outcome. Conclusions— Impaired renal function is independently associated with heightened risk for death, cardiovascular death, and hospitalization for heart failure in patients with CHF with both preserved as well as reduced LVEF. There was no evidence that the beneficial effect of candesartan was modified by baseline eGFR.
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Levey, A. S., Bosch, J. P., Lewis, J. B., Greene, T., Rogers, N., Roth, D., & for the Modification of Diet in Renal Disease Study Group* (1999) · Annals of Internal Medicine · doi:10.7326/0003-4819-130-6-199903160-00002 · Cited by 15,079 · see citing works
Brenner, B. M., Cooper, M. E., de Zeeuw, D., Keane, W. F., Mitch, W. E., Parving, H.-H., Remuzzi, G., Snapinn, S. M., Zhang, Z., & Shahinfar, S. (2001) · New England Journal of Medicine · doi:10.1056/nejmoa011161 · Cited by 7,493 · see citing works
Lewis, E. J., Hunsicker, L. G., Clarke, W. R., Berl, T., Pohl, M. A., Lewis, J. B., Ritz, E., Atkins, R. C., Rohde, R., & Raz, I. (2001) · New England Journal of Medicine · doi:10.1056/nejmoa011303 · Cited by 5,987 · see citing works
The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy
Lewis, E. J., Hunsicker, L. G., Bain, R. P., & Rohde, R. D. (1993) · New England Journal of Medicine · doi:10.1056/nejm199311113292004 · Cited by 5,394 · see citing works
Sarnak, M. J., Levey, A. S., Schoolwerth, A. C., Coresh, J., Culleton, B., Hamm, L. L., McCullough, P. A., Kasiske, B. L., Kelepouris, E., Klag, M. J., et al. (2003) · Circulation · doi:10.1161/01.cir.0000095676.90936.80 · Cited by 3,768 · see citing works
Self-citationYusuf, S., Pfeffer, M. A., Swedberg, K., Granger, C. B., Held, P., McMurray, J. J., Michelson, E. L., Olofsson, B., & Östergren, J. (2003) · The Lancet · doi:10.1016/s0140-6736(03)14285-7 · Cited by 2,994 · see citing works
Self-citationMcMurray, J. J., Östergren, J., Swedberg, K., Granger, C. B., Held, P., Michelson, E. L., Olofsson, B., Yusuf, S., & Pfeffer, M. A. (2003) · The Lancet · doi:10.1016/s0140-6736(03)14283-3 · Cited by 2,604 · see citing works
Self-citationRelation between Renal Dysfunction and Cardiovascular Outcomes after Myocardial Infarction
Anavekar, N. S., McMurray, J. J. V., Velazquez, E. J., Solomon, S. D., Køber, L., Rouleau, J. L., White, H. D., Nordlander, R., Maggioni, A. P., Dickstein, K., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa041365 · Cited by 1,913 · see citing works
Self-citationPfeffer, M. A., Swedberg, K. B., Granger, C. B., Held, P., McMurray, J. J. V., Michelson, E. L., Olofsson, B., Östergren, J., & Yusuf, S. (2003) · The Lancet · doi:10.1016/s0140-6736(03)14282-1 · Cited by 1,885 · see citing works
Self-citationMaschio, G., Alberti, D., Janin, G., Locatelli, F., Mann, J. F. E., Motolese, M., Ponticelli, C. E., Ritz, E., & Zucchelli, P. C. (1996) · New England Journal of Medicine · doi:10.1056/nejm199604113341502 · Cited by 1,743 · see citing works
Granger, C. B., McMurray, J. J., Yusuf, S., Held, P., Michelson, E. L., Olofsson, B., Östergren, J., Pfeffer, M. A., & Swedberg, K. (2003) · The Lancet · doi:10.1016/s0140-6736(03)14284-5 · Cited by 1,686 · see citing works
Self-citationGoodpasture syndrome during the course of a Schönlein-Henoch purpura
Carreras, L., Poveda, R., Bas, J., Mestre, M., Rama, I., & Carrera, M. (2002) · American Journal of Kidney Diseases · doi:10.1053/ajkd.2002.32799 · Cited by 1,474 · see citing works
Doqi, K. (2002) · American Journal of Kidney Diseases · Cited by 1,285 · see citing works
Jafar, T. H., Stark, P. C., Schmid, C. H., Landa, M., Maschio, G., de Jong, P. E., de Zeeuw, D., Shahinfar, S., Toto, R. D., Levey, A. S., et al. (2003) · Annals of Internal Medicine · doi:10.7326/0003-4819-139-4-200308190-00006 · Cited by 1,143 · see citing works
McMurray, J. J. V., Östergren, J., Swedberg, K. B., Granger, C. B., Held, P., Michelson, E. L., Olofsson, B., Yusuf, S., & Pfeffer (2003) · The Lancet · Cited by 1,043 · see citing works
Self-citationRenal Function, Neurohormonal Activation, and Survival in Patients With Chronic Heart Failure
Hillege, H. L., Girbes, A. R. J., de Kam, P. J., Boomsma, F., de Zeeuw, D., Charlesworth, A., Hampton, J., & van Veldhuisen, D. J. (2000) · Circulation · doi:10.1161/01.cir.102.2.203 · Cited by 1,041 · see citing works
Self-citationDries, D. L., Exner, D. V., DOMANSKI, M. J., Greenberg, B., & Stevenson, L. W. (2000) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(99)00608-7 · Cited by 874 · see citing works
Wolf, G., Chen, S., Han, D. C., & Ziyadeh, F. N. (2002) · American Journal of Kidney Diseases · doi:10.1053/ajkd.2002.29865 · Cited by 870 · see citing works
Cardiovascular disease and mortality in a community-based cohort with mild renal insufficiency
Culleton, B. F., Larson, M. G., Wilson, P. W. F., Evans, J. C., Parfrey, P. S., & Levy, D. A. (1999) · Kidney International · doi:10.1046/j.1523-1755.1999.00773.x · Cited by 834 · see citing works
Renal Insufficiency and Heart Failure
McAlister, F. A., Ezekowitz, J. A., Tonelli, M. A., & Armstrong, P. W. (2004) · Circulation · doi:10.1161/01.cir.0000116764.53225.a9 · Cited by 702 · see citing works
Al‐Ahmad, A., Rand, W. M., Manjunath, G., Konstam, M. A., Salem, D. N., Levey, A. S., & Sarnak, M. J. (2001) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(01)01470-x · Cited by 691 · see citing works
The endotoxin-lipoprotein hypothesis
Rauchhaus, M., Coats, A. J. S., & Anker, S. D. (2000) · The Lancet · doi:10.1016/s0140-6736(00)02690-8 · Cited by 544 · see citing works
Moderate renal insufficiency and the risk of cardiovascular mortality: Results from the NHANES I
Garg, A. X., Clark, W. F., Haynes, R. B., & House, A. A. (2002) · Kidney International · doi:10.1046/j.1523-1755.2002.00270.x · Cited by 309 · see citing works
Role of the Kidney in Congestive Heart Failure
Ljungman, S., Laragh, J., & Cody, R. J. (1990) · Drugs · doi:10.2165/00003495-199000394-00004 · Cited by 299 · see citing works
Prediction equations to estimate glomerular filtration rate: an update
Manjunath, G., Sarnak, M. J., & Levey, A. S. (2001) · Current Opinion in Nephrology & Hypertension · doi:10.1097/00041552-200111000-00009 · Cited by 276 · see citing works
Prevalence of Low Glomerular Filtration Rate in Nondiabetic Americans
Clase, C. M., Garg, A. X., & KIBERD, B. A. (2002) · Journal of the American Society of Nephrology · doi:10.1097/01.asn.0000013291.78621.26 · Cited by 222 · see citing works
Vasan, R. S., Beiser, A., D’Agostino, R. B., Levy, D. A., Selhub, J., Jacques, P. F., Rosenberg, I. H., & Wilson, P. W. F. (2003) · JAMA · doi:10.1001/jama.289.10.1251 · Cited by 213 · see citing works
Ljungman, S., Kjekshus, J., & Swedberg, K. (1992) · The American Journal of Cardiology · doi:10.1016/0002-9149(92)91194-9 · Cited by 193 · see citing works
Self-citationRenal function: the Cinderella of cardiovascular risk profile
Ruilope, L. M., van Veldhuisen, D. J., Ritz, E., & Lüscher, T. F. (2001) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(01)01627-8 · Cited by 193 · see citing works
Mahon, N., Blackstone, E. H., Francis, G. S., Starling, R. C., Young, J. B., & Lauer, M. S. (2002) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(02)02125-3 · Cited by 176 · see citing works
Leithe, M. E., Margorien, R. D., Hermiller, J. B., et al. (1984) · Circulation · doi:10.1161/01.cir.69.1.57 · Cited by 173 · see citing works
Knight, E. L., Glynn, R. J., McIntyre, K. M., Mogun, H., & Avorn, J. (1999) · American Heart Journal · doi:10.1016/s0002-8703(99)70009-8 · Cited by 164 · see citing works
Hillege, H. L. (2003) · European Heart Journal · doi:10.1016/s0195-668x(02)00526-2 · Cited by 164 · see citing works
Self-citationJones, R. C., Francis, G. S., & Lauer, M. S. (2004) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2004.05.077 · Cited by 128 · see citing works
Smilde, T. D. J., Hillege, H. L., Voors, A. A., Dunselman, P. H. J. M., & van Veldhuisen, D. J. (2004) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2004.03.075 · Cited by 43 · see citing works
Self-citationKambara, A., Holycross, B. J., Wung, P. K., et al. (2003) · Journal of Cardiovascular Pharmacology · doi:10.1097/00005344-200306000-00002 · Cited by 38 · see citing works
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Tang, W. H. W., Li, D. Y., & Hazen, S. L. (2019) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0108-7 · Cited by 789 · see citing works
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Kielstein, J. T., Salpeter, S. R., Bode-Boeger, S. M., Cooke, J. P., & Fliser, D. (2006) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfl292 · Cited by 363 · see citing works
Gerstein, H. C. (2008) · Archives of Internal Medicine · doi:10.1001/archinte.168.15.1699 · Cited by 217 · see citing works
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Damman, K., Tang, W. H. W., Felker, G. M., Lassus, J., Zannad, F., Krum, H., & McMurray, J. J. V. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.11.031 · Cited by 122 · see citing works
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Self-citation
- Authors
- Hillege, H. L., Nitsch, D., Pfeffer, M. A., Swedberg, K., McMurray, J. J. V., Yusuf, S., Granger, C. B., Michelson, E. L., Östergren, J., Cornel, J. H., de Zeeuw, D., Pocock, S., & van Veldhuisen, D. J.
- Affiliations
- Brigham and Women's Hospital (US)
- From the University Medical Center Groningen, University of Groningen, the Netherlands (H.L.H., D.J.V.V.); Medical Statistics Unit, London School of Hygiene and Tropical Medicine, London, UK (D.N., S.P.); The Cardiovascular Division, Brigham and Women’s Hospital, Boston, Mass (M.A.P.); Sahlgrenska University Hospital/Östra Göteborg, Sweden (K.S.); University of Glasgow, Glasgow, UK (J.J.V.M.); Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada (S.Y.); Duke University...
- Corresponding author
- Hillege, Hans L.
- ORCID
- Venue
- Circulation
- Published
- 2006-02-07
- Volume
- 113
- Issue
- 5
- Pages
- 671-678
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2144350847
- Cited by
- 945
- References
- 36
- Citations by year
- 2026: 21 · 2025: 32 · 2024: 35 · 2023: 44 · 2022: 35 · 2021: 35 · 2020: 44 · 2019: 37 · 2018: 31 · 2017: 45 · 2016: 44 · 2015: 68 · 2014: 51 · 2013: 51 · 2012: 68
- FWCI
- 39.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- AstraZeneca
- London School of Hygiene and Tropical Medicine
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- chronic heart failure, renal function, estimated glomerular filtration rate, left ventricular ejection fraction, cardiovascular mortality, heart failure hospitalization, all-cause mortality, prognosis, CHARM trial, ACE inhibitors, preserved ejection fraction, reduced ejection fraction, serum creatinine, MDRD equation, risk stratification, candesartan, renin-angiotensin system
- MeSH terms
- Aged, Benzimidazoles, Biphenyl Compounds, Female, Heart Failure, Hospitalization, Humans, Kidney Diseases, Kidney Function Tests, Male, Middle Aged, Prognosis, Risk Factors, Stroke Volume, Tetrazoles, Survival Analysis, Angiotensin II Type 1 Receptor Blockers
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