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Rapid Decline of Kidney Function Increases Cardiovascular Risk in the Elderly

Michael G. Shlipak^*, Ronit Katz, Bryan Kestenbaum, David Siscovick, Linda Fried^||, Anne Newman^¶, Dena Rifkin^** and Mark J. Sarnak^**

^* General Internal Medicine Section, San Francisco VA Medical Center and Departments of Medicine, Epidemiology, and Biostatistics, University of California, San Francisco, San Francisco, California;
Collaborative Health Studies Coordinating Center,
Nephrology Division, School of Medicine, and
Departments of Medicine and Epidemiology, University of Washington, Seattle, Washington;
^|| Renal Section, Medical Service, VA Pittsburgh Healthcare System, Pittsburgh Pennsylvania;
^¶ 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
^** Division of Nephrology, Department of Medicine, Tufts-New England Medical Center, Boston, Massachusetts

Correspondence: Dr. Michael Shlipak, 4150 Clement Street, 111A1, San Francisco, CA 94121. Phone: 415-221-4810, ext. 3381; Fax: 415-379-5573; E-mail: michael.shlipak{at}ucsf.edu

Received for publication May 26, 2009. Accepted for publication August 5, 2009.

Chronic kidney disease (CKD), defined at a specific time point, is an important risk factor for cardiovascular disease. Whether the rate of kidney function decline contributes additional cardiovascular risk is unknown. In the Cardiovascular Health Study, we compared the associations of changes in kidney function during the first 7 yr with the incidence of heart failure (HF), myocardial infarction (MI), stroke, and peripheral arterial disease (PAD) during the subsequent 8 yr. We defined a rapid decline in cystatin C–based estimated GFR as >3 ml/min per 1.73 m²/yr, on the basis of determination at baseline, year 3, and year 7. Among eligible participants, 1083 (24%) had rapid kidney decline. The incidence of each type of cardiovascular event was significantly higher among patients with rapid decline (all P < 0.001). After multivariate adjustment for demographics, cardiovascular disease risk factors, and baseline kidney function, rapid kidney function decline was significantly associated with HF (adjusted hazard ratio [HR] 1.32; 95% confidence interval [CI] 1.13 to 1.53), MI (HR 1.48; 95% CI 1.21 to 1.83), and PAD (HR 1.67; 95% CI 1.02 to 2.75) but not with stroke (HR 1.19; 95% CI 0.97 to 1.45). The association of rapid decline with each outcome did not differ by the presence or absence of CKD. In conclusion, declining kidney function associates with higher risk for HF, MI, and PAD among patients with or without CKD.

Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673