European Heart Journal Advance Access originally published online on May 31, 2009
European Heart Journal 2009 30(15):1918-1925; doi:10.1093/eurheartj/ehp195
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Kidney function estimated from serum creatinine and cystatin C and peripheral arterial disease in NHANES 1999–2002
1 Department of Epidemiology and the Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, 2024 E. Monument Street, Suite 2-600, Baltimore, MD 21287, USA
2 Division of General Internal Medicine, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA
* Corresponding author. Tel: +1 410 614 3752, Fax: +1 410 955 0476, Email: lselvin{at}jhsph.edu
Aims: Serum cystatin C, a novel marker of kidney function, is reported to be superior to serum creatinine as a risk factor for atherosclerotic disease, but associations may vary across vascular beds.
Methods and results: A cross-sectional study of chronic kidney disease (CKD) and peripheral arterial disease (PAD) in 3089 adult participants aged 40+ from the 1999–2002 National Health and Nutrition Examination Survey (NHANES). Kidney function, assessed by estimated glomerular filtration rate (eGFR), was determined from serum creatinine and cystatin C using established equations. Peripheral arterial disease defined by an ankle brachial index <0.90. Glomerular filtration rate estimated using cystatin C was more strongly associated with PAD compared with eGFR using serum creatinine before and after multivariable adjustment. Further, after adjustment for cystatin C, kidney function based on serum creatinine was no longer significantly associated with PAD. However, cystatin C remained significantly associated with PAD even after adjustment for GFR estimated by serum creatinine. Compared with optimal kidney function (eGFRserum creatinine 
60, eGFRcystatin C >90), the odds ratio for PAD was 3.11 (95% confidence interval 1.26–7.64) for preclinical CKD (eGFRserum creatinine 60, eGFRcystatin C <76.7) and 5.07 (3.01–8.52) for ‘confirmed’ CKD (eGFRserum creatinine <60, eGFRcystatin C <60).
Conclusion: Chronic kidney disease was strongly and independently associated with PAD. Cystatin C was a more potent marker of lower extremity PAD when compared with the serum creatinine equation currently used in clinical practice. Our results suggest that cystatin C may have clinical utility when combined with serum creatinine in evaluation of individuals who may have PAD.
Key Words: Peripheral arterial disease • Chronic kidney disease • glomerular filtration rate • Cystatin C • Epidemiology • NHANES