CLINICAL STUDY: CARDIAC ISSUES IN WOMEN AND THE ELDERLY
Renal insufficiency as a predictor of cardiovascular outcomes and mortality in elderly individuals
Linda F. Fried, MD, MPH* ,*,
Michael G. Shlipak, MD, MPH  ,
Casey Crump, MD, PhD||,
Anthony J. Bleyer, MD¶,
John S. Gottdiener, MD, FACC#,
Richard A. Kronmal, PhD||,
Lewis H. Kuller, MD, DrPH, FACC** and
Anne B. Newman, MD, MPH**
* Renal Section, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA
Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
Medicine Service, Veterans Affairs Medical Center, San Francisco, California, USA
Departments of Medicine, Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA
|| Department of Biostatistics, University of Washington, Seattle, Washington, USA
¶ Section of Nephrology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
# Division of Cardiology, St. Francis Hospital, Roslyn, New York, USA
** Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania, USA
Division of Geriatric Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
Manuscript received May 20, 2002;
revised manuscript received December 4, 2002,
accepted December 30, 2002.
* Reprint requests and correspondence: Dr. Linda F. Fried, VA Pittsburgh Healthcare System, 111F-U, University Drive C, Pittsburgh, Pennsylvania 15240, USA.
lff9+{at}pitt.edu
OBJECTIVES: This study was designed to evaluate the relationship between elevated creatinine levels and cardiovascular events.
BACKGROUND: End-stage renal disease is associated with high cardiovascular morbidity and mortality. The association of mild to moderate renal insufficiency with cardiovascular outcomes remains unclear.
METHODS: We analyzed data from the Cardiovascular Health Study, a prospective population-based study of subjects, aged >65 years, who had a serum creatinine measured at baseline (n = 5,808) and were followed for a median of 7.3 years. Proportional hazards models were used to examine the association of creatinine to all-cause mortality and incident cardiovascular mortality and morbidity. Renal insufficiency was defined as a creatinine level  1.5 mg/dl in men or 1.3 mg/dl in women.
RESULTS: An elevated creatinine level was present in 648 (11.2%) participants. Subjects with elevated creatinine had higher overall (76.7 vs. 29.5/1,000 years, p < 0.001) and cardiovascular (35.8 vs. 13.0/1,000 years, p < 0.001) mortality than those with normal creatinine levels. They were more likely to develop cardiovascular disease (54.0 vs. 31.8/1,000 years, p < 0.001), stroke (21.1 vs. 11.9/1,000 years, p < 0.001), congestive heart failure (38.7 vs. 17/1,000 years, p < 0.001), and symptomatic peripheral vascular disease (10.6 vs. 3.5/1,000 years, p < 0.001). After adjusting for cardiovascular risk factors and subclinical disease measures, elevated creatinine remained a significant predictor of all-cause and cardiovascular mortality, total cardiovascular disease (CVD), claudication, and congestive heart failure (CHF). A linear increase in risk was observed with increasing creatinine.
CONCLUSIONS: Elevated creatinine levels are common in older adults and are associated with increased risk of mortality, CVD, and CHF. The increased risk is apparent early in renal disease.
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Abbreviations and Acronyms
| | AAI | | ankle-arm index | | CHF | | congestive heart failure | | CHS | | Cardiovascular Health Study | | CI | | confidence interval | | CRP | | C-reactive protein | | CVD | | cardiovascular disease | | HDL | | high-density lipoprotein | | HR | | hazards ratio | | IMT | | intima-media thickness | | LDL | | low-density lipoprotein | | MI | | myocardial infarction |
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M. J. Sarnak, R. Katz, C. O. Stehman-Breen, L. F. Fried, N. S. Jenny, B. M. Psaty, A. B. Newman, D. Siscovick, M. G. Shlipak, and and the Cardiovascular Health Study*
Cystatin C Concentration as a Risk Factor for Heart Failure in Older Adults
Ann Intern Med,
April 5, 2005;
142(7):
497 - 505.
[Abstract]
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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]
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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]
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R. N. Foley, A. M. Murray, S. Li, C. A. Herzog, A. M. McBean, P. W. Eggers, and A. J. Collins
Chronic Kidney Disease and the Risk for Cardiovascular Disease, Renal Replacement, and Death in the United States Medicare Population, 1998 to 1999
J. Am. Soc. Nephrol.,
February 1, 2005;
16(2):
489 - 495.
[Abstract]
[Full Text]
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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.
[Abstract]
[Full Text]
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W. Koenig, D. Twardella, H. Brenner, and D. Rothenbacher
Plasma Concentrations of Cystatin C in Patients with Coronary Heart Disease and Risk for Secondary Cardiovascular Events: More than Simply a Marker of Glomerular Filtration Rate
Clin. Chem.,
February 1, 2005;
51(2):
321 - 327.
[Abstract]
[Full Text]
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M. S. Edwards, T. E. Craven, G. L. Burke, R. H. Dean, and K. J. Hansen
Renovascular Disease and the Risk of Adverse Coronary Events in the Elderly: A Prospective, Population-Based Study
Arch Intern Med,
January 24, 2005;
165(2):
207 - 213.
[Abstract]
[Full Text]
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L. G. Bongartz, M. J. Cramer, P. A. Doevendans, J. A. Joles, and B. Braam
The severe cardiorenal syndrome: 'Guyton revisited'
Eur. Heart J.,
January 1, 2005;
26(1):
11 - 17.
[Abstract]
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M. R. Jaff
Expert Commentary
Perspectives in Vascular Surgery and Endovascular Therapy,
December 1, 2004;
16(4):
258 - 260.
[PDF]
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L. Fried, C. Solomon, M. Shlipak, S. Seliger, C. Stehman-Breen, A. J. Bleyer, P. Chaves, C. Furberg, L. Kuller, and A. Newman
Inflammatory and Prothrombotic Markers and the Progression of Renal Disease in Elderly Individuals
J. Am. Soc. Nephrol.,
December 1, 2004;
15(12):
3184 - 3191.
[Abstract]
[Full Text]
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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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A. M. O'Hare, E. Vittinghoff, J. Hsia, and M. G. Shlipak
Renal Insufficiency and the Risk of Lower Extremity Peripheral Arterial Disease: Results from the Heart and Estrogen/Progestin Replacement Study (HERS)
J. Am. Soc. Nephrol.,
April 1, 2004;
15(4):
1046 - 1051.
[Abstract]
[Full Text]
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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]
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G. A. Kaysen and J. P. Eiserich
The Role of Oxidative Stress-Altered Lipoprotein Structure and Function and Microinflammation on Cardiovascular Risk in Patients with Minor Renal Dysfunction
J. Am. Soc. Nephrol.,
March 1, 2004;
15(3):
538 - 548.
[Abstract]
[Full Text]
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A. M. O'Hare, D. V. Glidden, C. S. Fox, and C.-y. Hsu
High Prevalence of Peripheral Arterial Disease in Persons With Renal Insufficiency: Results From the National Health and Nutrition Examination Survey 1999-2000
Circulation,
January 27, 2004;
109(3):
320 - 323.
[Abstract]
[Full Text]
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A. Clerico and M. Emdin
Diagnostic Accuracy and Prognostic Relevance of the Measurement of Cardiac Natriuretic Peptides: A Review
Clin. Chem.,
January 1, 2004;
50(1):
33 - 50.
[Abstract]
[Full Text]
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J. H. Ix, M. G. Shlipak, H. H. Liu, N. B. Schiller, and M. A. Whooley
Association between Renal Insufficiency and Inducible Ischemia in Patients with Coronary Artery Disease: The Heart and Soul Study
J. Am. Soc. Nephrol.,
December 1, 2003;
14(12):
3233 - 3238.
[Abstract]
[Full Text]
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C. A. Herzog
How to Manage the Renal Patient with Coronary Heart Disease: The Agony and the Ecstasy of Opinion-Based Medicine
J. Am. Soc. Nephrol.,
October 1, 2003;
14(10):
2556 - 2572.
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J J Santopinto, K A A Fox, R J Goldberg, A Budaj, G Pinero, A Avezum, D Gulba, J Esteban, J M Gore, J Johnson, et al.
Creatinine clearance and adverse hospital outcomes in patients with acute coronary syndromes: findings from the global registry of acute coronary events (GRACE)
Heart,
September 1, 2003;
89(9):
1003 - 1008.
[Abstract]
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