Limited Value of Cystatin-C over Estimated Glomerular Filtration Rate for Heart Failure Risk Stratification Elisabet Zamora 1,2 , Josep Lupo ´n 1,2 , Marta de Antonio 1,2 , Joan Vila 3,4 , Amparo Gala ´n 5 , Paloma Gastelurrutia 1 , Agustı´n Urrutia 1,2 , Antoni Bayes-Genis 1,2 * 1 Heart Failure Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Spain, 2 Department of Medicine, Autonomous University of Barcelona, Barcelona, Spain, 3 Inflammatory and Cardiovascular Disease Programme, IMIM-Hospital del Mar Research Institute, Barcelona, Spain, 4 CIBER Epidemiology and Public Health, Barcelona, Spain, 5 Biochemistry Service, Hospital Universitari Germans Trias i Pujol, Badalona, Spain Abstract Background: To compare the prognostic value of estimated glomerular filtration rate, cystatin-C, an alternative renal biomarker, and their combination, in an outpatient population with heart failure.Estimated glomerular filtration rate is routinely used to assess renal function in heart failure patients. We recently demonstrated that the Cockroft-Gault formula is the best among the most commonly used estimated glomerular filtration rate formulas for predicting heart failure prognosis. Methodology/Principal Findings: A total of 879 consecutive patients (72% men, age 70.4 years [P 25–75 60.5–77.2]) were studied. The etiology of heart failure was mainly ischemic heart disease (52.7%). The left ventricular ejection fraction was 34% (P 25–75 26–43%). Most patients were New York Heart Association class II (65.8%) or III (25.9%). During a median follow- up of 3.46 years (P 25–75 1.85–5.05), 312 deaths were recorded. In an adjusted model, estimated glomerular filtration rate and cystatin-C showed similar prognostic value according to the area under the curve (0.763 and 0.765, respectively). In Cox regression, the multivariable analysis hazard ratios were 0.99 (95% CI: 0.98–1, P = 0.006) and 1.14 (95% CI: 1.02–1.28, P = 0.02) for estimated glomerular filtration rate and cystatin-C, respectively. Reclassification, assessed by the integration discrimination improvement and the net reclassification improvement indices, was poorer with cystatin-C (20.5 [21.0;20.1], P = 0.024 and 24.9 [28.8;21.0], P = 0.013, respectively). The value of cystatin-C over estimated glomerular filtration rate for risk-stratification only emerged in patients with moderate renal dysfunction (eGFR 30–60 ml/min/1.73 m 2 , chi-square 12.9, P,0.001). Conclusions/Significance: Taken together, the results indicate that estimated glomerular filtration rate and cystatin-C have similar long-term predictive values in a real-life ambulatory heart failure population. Cystatin-C seems to offer improved prognostication in heart failure patients with moderate renal dysfunction. Citation: Zamora E, Lupo ´ n J, de Antonio M, Vila J, Gala ´ n A, et al. (2012) Limited Value of Cystatin-C over Estimated Glomerular Filtration Rate for Heart Failure Risk Stratification. PLoS ONE 7(12): e51234. doi:10.1371/journal.pone.0051234 Editor: Michael Lipinski, University of Virginia Health System, United States of America Received September 27, 2012; Accepted October 30, 2012; Published December 11, 2012 Copyright: ß 2012 Zamora et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: Cystatin-C assays were provided by Radim Ibe ´rica (Barcelona, Spain) which had no role in the design of the study or the collection, management, analysis, interpretation or writing of the data. Dr. M. de Antonio received a competitive research grant from the Catalan Society of Cardiology (Barcelona, Spain). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: abayesgenis@gmail.com Introduction Chronic heart failure (HF) is a growing public epidemic with increasing incidence and prevalence [1]. Despite important progress in recent decades, mortality remains high among patients with HF. Renal insufficiency is prevalent among patients with HF, and the coexistence of both conditions results in a worse prognosis [2–6]. The most precise methods for calculating kidney function, including the isotopic glomerular filtration rate and creatinine clearance in a 24-hour urine specimen, are not utilized in daily clinical practice [7]. Instead, several formulas based on creatinine clearance have been developed to determine the estimated glomerular filtration rate (eGFR), with the Cockroft-Gault formula [8], the simplified Modification of Diet in Renal Disease (MDRD- 4) equation [9], and the Chronic Kidney Disease Epidemiology Collaboration equation [10] being the most commonly used in clinical practice. We recently demonstrated that the Cockroft- Gault formula is the best among these three eGFR formulas for predicting long-term prognosis in HF patients [11]. In the last few years, cystatin-C has emerged as a novel renal biomarker with prognostic implications in patients with HF [12– 13]. However, to the best of our knowledge, no data have assessed the benefits of cystatin-C over eGFR in terms of prognosis in patients with chronic HF. The objective of the present study was to compare the long-term prognostic value of cystatin-C and eGFR using the Cockroft-Gault formula in an outpatient population with HF and to assess whether the simultaneous use of both markers is helpful in improving patient risk stratification. PLOS ONE | www.plosone.org 1 December 2012 | Volume 7 | Issue 12 | e51234