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Original Article
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Volume 352:2049-2060 May 19, 2005 Number 20
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Cystatin C and the Risk of Death and Cardiovascular Events among Elderly Persons
Michael G. Shlipak, M.D., M.P.H., Mark J. Sarnak, M.D., Ronit Katz, Ph.D., Linda F. Fried, M.D., M.P.H., Stephen L. Seliger, M.D., Anne B. Newman, M.D., M.P.H., David S. Siscovick, M.D., M.P.H., and Catherine Stehman-Breen, M.D.

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ABSTRACT

Background Cystatin C is a serum measure of renal function that appears to be independent of age, sex, and lean muscle mass. We compared creatinine and cystatin C levels as predictors of mortality from cardiovascular causes and from all causes in the Cardiovascular Health Study, a cohort study of elderly persons living in the community.

Methods Creatinine and cystatin C were measured in serum samples collected from 4637 participants at the study visit in 1992 or 1993; follow-up continued until June 30, 2001. For each measure, the study population was divided into quintiles, with the fifth quintile subdivided into thirds (designated 5a, 5b, and 5c).

Results Higher cystatin C levels were directly associated, in a dose–response manner, with a higher risk of death from all causes. As compared with the first quintile, the hazard ratios (and 95 percent confidence intervals) for death were as follows: second quintile, 1.08 (0.86 to 1.35); third quintile, 1.23 (1.00 to 1.53); fourth quintile, 1.34 (1.09 to 1.66); quintile 5a, 1.77 (1.34 to 2.26); 5b, 2.18 (1.72 to 2.78); and 5c, 2.58 (2.03 to 3.27). In contrast, the association of creatinine categories with mortality from all causes appeared to be J-shaped. As compared with the two lowest quintiles combined (cystatin C level, ≤0.99 mg per liter), the highest quintile of cystatin C (≥1.29 mg per liter) was associated with a significantly elevated risk of death from cardiovascular causes (hazard ratio, 2.27 [1.73 to 2.97]), myocardial infarction (hazard ratio, 1.48 [1.08 to 2.02]), and stroke (hazard ratio, 1.47 [ 1.09 to 1.96]) after multivariate adjustment. The fifth quintile of creatinine, as compared with the first quintile, was not independently associated with any of these three outcomes.

Conclusions Cystatin C, a serum measure of renal function, is a stronger predictor of the risk of death and cardiovascular events in elderly persons than is creatinine.


Source Information

From the General Internal Medicine Section, Veterans Affairs Medical Center, and the Departments of Medicine and Epidemiology and Biostatistics, University of California, San Francisco — both in San Francisco (M.G.S.); the Division of Nephrology, Department of Medicine, Tufts–New England Medical Center, Boston (M.J.S.); the Collaborative Health Studies Coordinating Center, Seattle (R.K.); the Renal Section, Medical Service, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh (L.F.F.); the Division of Nephrology, University of Maryland School of Medicine, Baltimore (S.L.S.); the Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, and the Division of Geriatric Medicine, University of Pittsburgh School of Medicine, Pittsburgh (A.B.N.); the Departments of Medicine and Epidemiology, University of Washington, Seattle (D.S.S.); and Amgen, Thousand Oaks, Calif. (C.S.-B.).

Address reprint requests to Dr. Shlipak at the General Internal Medicine Section, Veterans Affairs Medical Center (111A1), 4150 Clement St., San Francisco, CA 94121 or at shlip{at}itsa.ucsf.edu.

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Related Letters:

Cystatin C and the Risk of Death
Berghout A., Wulkan R. W., den Hollander J. G., Risch L., Drexel H., Huber A. R., Perkins B. A., Nelson R. G., Krolewski A. S., Shlipak M. G., Sarnak M. J., Fried L. F.
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N Engl J Med 2005; 353:842-844, Aug 25, 2005. Correspondence

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