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Mark J. Sarnak, MD, MS; Ronit Katz, DPhil; Linda F. Fried, MD, MPH; David Siscovick, MD, MPH; Brian Kestenbaum, MD, MS; Stephen Seliger, MD, MS; Dena Rifkin, MD; Russell Tracy, PhD; Anne B. Newman, MD; Michael G. Shlipak, MD, MPH; for the Cardiovascular Health Study

Arch Intern Med. 2008;168(2):147-153.

Background  To our knowledge, the effect of kidney function on successful aging has not been examined.

Methods  We evaluated the relationship between cystatin C and aging success during a 6-year follow-up in the Cardiovascular Health Study, a community-based cohort of older adults (aged 65 years). Successful aging was defined as remaining free of cardiovascular disease, cancer, and chronic obstructive pulmonary disease and having intact physical and cognitive functioning. In adjusted analysis, an accelerated failure time model was used to evaluate the percentage reduction in successful years by level of cystatin C. A separate Cox proportional hazards model evaluated whether cystatin C was related to incident physical and cognitive disability.

Results  A total of 2140 participants had cystatin C measured and were free of the previously mentioned conditions at baseline. Their mean age was 74 years. The mean cystatin C level, creatinine level, and estimated glomerular filtration rate were 1.06 mg/L, 0.93 mg/dL, and 78 mL/min/1.73 m², respectively (to convert cystatin C to nanomoles per liter, multiply by 75; and to convert creatinine to micromoles per liter, multiply by 88.4). A total of 873 participants reached a first event in follow-up, 138 because of cognitive disability, 238 because of physical disability, 34 because of chronic obstructive pulmonary disease, 146 because of cancer, and 317 because of cardiovascular disease. The adjusted percentage reduction in successful life years in the highest vs the lowest quartile of cystatin C was 27% (95% confidence interval, 11%-39%). The highest vs lowest quartile of cystatin C also was independently associated with incident cognitive or physical disability (hazard ratio, 1.39; 95% confidence interval, 1.00-1.98).

Conclusion  A higher cystatin C level, even within a range of relatively normal kidney function, was associated with unsuccessful aging.

Author Affiliations: Department of Medicine, Tufts–New England Medical Center, Boston, Massachusetts (Drs Sarnak and Rifkin); Collaborative Health Studies Coordinating Center, Seattle, Washington (Drs Katz and Siscovick); Departments of Biostatistics (Dr Katz), Medicine (Drs Siscovick and Kestenbaum), and Epidemiology (Dr Siscovick), University of Washington, Seattle; Departments of Medicine (Drs Fried and Newman) and Epidemiology (Dr Newman), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Department of Medicine, University of Maryland, Baltimore (Dr Seliger); Department of Pathology, University of Vermont College of Medicine, Burlington (Dr Tracy); and Department of Medicine, San Francisco Veterans Administration and University of California, San Francisco (Dr Shlipak).
Group Information: A list of participating Cardiovascular Health Study investigators and institutions can be found at http://www.chs-nhlbi.org.

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