Cystatin C and Long-Term Mortality Among Subjects With Normal Creatinine-Based Estimated Glomerular Filtration Rates

Objectives The objective was to test the association of cystatin C (Cys-C) with long-term mortality risk in the subjects with normal creatinine-based estimated glomerular filtration rates (eGFR). Background Cys-C has been proposed as a sensitive indicator of renal dysfunction that is associated with cardiovascular events. The predictive value of Cys-C for mortality risk (both cardiovascular and noncardiovascular) and its utility among persons with normal kidney function remains unclear. Methods The analysis included 2,990 subjects over 40 years of age with normal eGFR who participated in NHANES III (Third National Health and Nutrition Examination Survey). Normal eGFR was defined by Modification of Diet in Renal Disease (MDRD) equation >= 60 ml/min/1.73 m(2). Serum Cys-C was categorized as high, medium, or low. In 1 analysis, the high and low groups were the top and bottom 10%, and in the second analysis, they were the upper and lower thirds. All-cause and cause-specific mortality were obtained from the NHANES III-linked follow-up file through December 31, 2006. Multivariate Cox regression models were applied to assess the association of interest. Results Within an average of 13.7 years follow-up, 488 cardiovascular and 719 noncardiovascular deaths occurred. When the first and last deciles were compared, the relative risks were all increased statistically as follows: allcause, 4.36 (95% confidence interval [CI]: 2.52 to 7.82); cardiovascular, 7.44 (95% CI: 3.06 to 18.1); cancer, 2.45 (95% CI: 0.85 to 7.04); and noncardiovascular 3.15 (95% CI: 1.53 to 6.49) mortalities. Relative risks all moderated to lower values when the comparisons were expanded to include the upper and lower thirds. Similar associations were still present when Cys-C was modeled on a continuous scale, suggesting a linear relationship between Cys-C and mortality outcomes. Conclusions Serum Cys-C is prognostic of long-term mortality in the subjects with relatively normal renal function, independent of MDRD eGFR and albuminuria. (J Am Coll Cardiol 2010;56:1930-6) (C) 2010 by the American College of Cardiology Foundation