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Published ahead of print on November 2, 2005
J Am Soc Nephrol 17: 254-261, 2006
© 2006 American Society of Nephrology
doi: 10.1681/ASN.2005050545

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Epidemiology and Outcomes

Cystatin C and Mortality Risk in the Elderly: The Health, Aging, and Body Composition Study

Michael G. Shlipak*,{dagger}, Christina L. Wassel Fyr{dagger}, Glenn M. Chertow{dagger}, Tamara B. Harris{ddagger}, Stephen B. Kritchevsky§, Frances A. Tylavsky||, Suzanne Satterfield||, Steven R. Cummings{dagger}, Anne B. Newman# and Linda F. Fried**

* General Internal Medicine Section, Veterans Affairs Medical Center, San Francisco, California; {dagger} Departments of Medicine, Epidemiology, and Biostatistics, University of California, San Francisco, California; {ddagger} Laboratory of Epidemiology, Demography and Biometry, Intramural Research Program, National Institute on Aging, Bethesda, Maryland; § J. Paul Sticht Center on Aging and Rehabilitation, Wake Forest Bowman Gray School of Medicine, Winston-Salem, North Carolina; || Department of Preventive Medicine, University of Tennessee, Memphis, Tennessee; California Pacific Medical Center Research Institute, San Francisco, California; # Department of Epidemiology, University of Pittsburgh Graduate School of Public Health and the Division of Geriatric Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and ** The Renal-Electrolyte Division, University of Pittsburgh School of Medicine, and the Renal Section, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania

Address correspondence to: Dr. Michael G. Shlipak, University of San Francisco, General Internal Medicine Section, VA Medical Center (111A1), 4150 Clement Street, San Francisco, CA 94121. Phone: 415-750-2093; Fax: 415-379-5573; shlip{at}itsa.ucsf.edu

Received for publication May 24, 2005. Accepted for publication September 27, 2005.

Kidney dysfunction is known to decrease life expectancy in the elderly. Cystatin C is a novel biomarker of kidney function that may have prognostic utility in older adults. The association of cystatin C with mortality was evaluated in a biracial cohort of black and white ambulatory elderly and compared with that of serum creatinine concentrations. The Health, Aging and Body Composition study is a cohort of well-functioning elderly that was designed to evaluate longitudinal changes in weight, body composition, and function. A total of 3075 participants who were aged 70 to 79 yr and had no disability were recruited at sites in Memphis, TN, and Pittsburgh, PA, between April 1997 and June 1998 with a follow-up of 6 yr. At entry, the mean cystatin C was 1.05 mg/L and the mean creatinine was 1.06 mg/dl. After 6 yr of follow-up, 557 participants had died. The mortality rates in each ascending cystatin C quintile were 1.7, 2.7, 2.9, 3.1, and 5.4%/yr. After adjustment for demographic risk factors, comorbid health conditions, and inflammatory biomarkers (C-reactive protein, IL-6. and TNF-{alpha}), each quintile of cystatin C was significantly associated with increased mortality risk compared with the lowest: Hazard ratios (HR; 95% confidence intervals) quintile 1, –1.0 (referent); quintile 2, –1.74 (1.21 to 2.50); quintile 3, –1.51 (1.05 to 2.18); quintile 4, –1.49 (1.04 to 2.13); and quintile 5, –2.18 (1.53 to 3.10). These associations did not differ by gender or race. Results were consistent for cardiovascular and other-cause mortality, but not cancer mortality. Creatinine quintiles were not associated with mortality after multivariate adjustment (HR: 1.0 [referent], 1.00 [0.72 to 1.39], 0.95 [0.68 to 1.32], 1.11 [0.79 to 1.57], 1.16 [0.86 to 1.58]). Cystatin C is a strong, independent risk factor for mortality in the elderly. Future studies should investigate whether cystatin C has a role in clinical medicine.


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