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Results From the Cardiovascular Health Study

Ann M. O’Hare, MD, MA; Anne B. Newman, MD, MPH; Ronit Katz, PhD; Linda F. Fried, MD; Catherine O. Stehman-Breen, MD; Stephen L. Seliger, MD; David S. Siscovick, MD; Michael G. Shlipak, MD, MPH

Arch Intern Med. 2005;165:2666-2670.

Background  The association of cystatin C, a novel marker of renal function, with risk for developing complications related to peripheral arterial disease (PAD) has not been examined.

Methods  We evaluated the hypothesis that a high cystatin C concentration is independently associated with future PAD events among 4025 participants in the Cardiovascular Health Study who underwent serum cystatin C measurement at the 1992-1993 visit and who did not have PAD at baseline. The association of cystatin C quintiles with time to first lower-extremity PAD procedure (bypass surgery, angioplasty, or amputation) was evaluated using multivariable proportional hazards models. Secondary analyses were conducted using quintiles of serum creatinine level and estimated glomerular filtration rate (eGFR).

Results  The annualized risk of undergoing a procedure for PAD was 0.43% per year among participants in the highest cystatin C quintile (>1.27 mg/L) compared with 0.21% per year or less in all other quintiles. After multivariable adjustment for known risk factors for PAD, elevated cystatin C levels remained associated with the outcome (hazard ratio, 2.5 for highest vs lowest quintile of cystatin C, 95% confidence interval, 1.2-5.1). The highest quintiles of serum creatinine level and eGFR were not associated with future PAD events in either unadjusted or adjusted analyses.

Conclusion  Elevated concentrations of cystatin C were independently predictive of incident PAD events among community-dwelling elderly patients.

Author Affiliations: Nephrology Division, Department of Medicine (Dr O’Hare), and General Internal Medicine Section (Dr Shlipak), Veterans Affairs Medical Center, San Francisco, and Nephrology Division, Department of Medicine (Dr O’Hare), and Departments of Medicine and Epidemiology and Biostatistics (Dr Shlipak), University of California, San Francisco; Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, and the Division of Geriatric Medicine (Dr Newman), and the Renal-Electrolyte Division (Dr Fried), University of Pittsburgh School of Medicine, and the Renal Section, Veterans Affairs Pittsburgh Healthcare System (Dr Fried), Pittsburgh, Pa; Collaborative Health Studies Coordinating Center (Dr Katz) and Departments of Medicine (Dr Seliger) and Medicine, Epidemiology, and Health Services (Dr Siscovick), University of Washington, Seattle; and Amgen Inc, Thousand Oaks, Calif (Dr Stehman-Breen).

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