Cystatin C and the Risk of Death and Cardiovascular Events among Elderly Persons

doi:10.1056/NEJMoa043161

Volume 352:2049-2060		May 19, 2005		Number 20

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 thatappears to be independent of age, sex, and lean muscle mass.We compared creatinine and cystatin C levels as predictors ofmortality from cardiovascular causes and from all causes inthe Cardiovascular Health Study, a cohort study of elderly personsliving in the community.

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

Results Higher cystatin C levels were directly associated, ina dose–response manner, with a higher risk of death fromall causes. As compared with the first quintile, the hazardratios (and 95 percent confidence intervals) for death wereas 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); quintile5a, 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 categorieswith mortality from all causes appeared to be J-shaped. As comparedwith the two lowest quintiles combined (cystatin C level, $≤$ 0.99mg per liter), the highest quintile of cystatin C ( $≥$ 1.29 mg perliter) was associated with a significantly elevated risk ofdeath from cardiovascular causes (hazard ratio, 2.27 [1.73 to2.97]), myocardial infarction (hazard ratio, 1.48 [1.08 to 2.02]),and stroke (hazard ratio, 1.47 [ 1.09 to 1.96]) after multivariateadjustment. The fifth quintile of creatinine, as compared withthe first quintile, was not independently associated with anyof these three outcomes.

Conclusions Cystatin C, a serum measure of renal function, isa stronger predictor of the risk of death and cardiovascularevents 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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N Engl J Med 2005; 353:842-844, Aug 25, 2005. Correspondence

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