Abstract
Background: Cystatin C (Cys-C) is a sensitive biomarker of renal function and an independent predictor of all-cause mortality (ACM) in patients with chronic kidney and cardiovascular disease (CVD). Although higher levels of Cys-C are associated with increased body mass index (BMI), the interplay between serum Cys-C, BMI and ACM in adults with normal renal function is unknown. Methods: Utilizing data from the National Health and Nutrition Examination Survey (1999-2002), analysis was conducted on participants (≥18 years) with normal renal function [glomerular filtration rate (GFR) ≥90 ml/min)]. BMI (kg/m2) was categorized as Normal (BMI:18.5-24.9); Overweight (BMI:25-29.9); Obese (BMI >30), while Cys-C (mg/L) was categorized into weight based quartiles [Q1:<0.72(ref); Q2: ≥0.72-0.80; Q3: ≥0.80-0.89; Q4: ≥0.89]. Mortality information was obtained from the National Death Index using probabilistic matching. Cox proportional hazards models (and associated 95% CI’s) estimated the likelihood of ACM by Cys-C quartiles in each BMI category. Results: The mean(±) age and GFR of 2649 participants (51% females) was 50±20 years and 123±28 mL/min, while the median (IQR) of CRP and Cys-C was 0.19(0.07-0.44) mg/dL and 0.80(0.72-0.89) mg/L, respectively. Approximately, 33% of the cohort was normal, 34% overweight, and 33% were obese. After a mean(SD) follow up of 5.9(1.3) years, 213 deaths (all-cause) were observed. Cys-C levels increased with increasing BMI (p trend <0.05), however, significant difference was only seen in obese when compared with normal weight adults (p<0.05). Within each BMI category, increasing Cys-C was associated with increased risk of ACM (p trend <0.05), however, the hazard ratio were statistically significant only at elevated Cys-C levels (Q4 vs.Q1) in normal and overweight adults (both p values <0.05). Conclusions: Independent of traditional CVD risk factors, elevated Cys-C levels predicts risk of ACM in normal and overweight but not in obese adults who have normal renal function based on GFR.
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