Clinical Significance And Influential Factors Of Serum Cystatin C In Healthy Population

Background and Objectives Cystatin C (CysC) is a novel endogenous biomarker to estimate glomerular filtration rate (GFR) recently. Past research has shown that GFR estimates using CysC are superior to serum creatinine in adult patients, and it is not influenced by race, gender, age, drugs, etc. But in recent years, researchers have confirmed that the effects of race, age and gender on serum CysC levels and GFR are not associated with carotid atherosclerosis in healthy population.In addition to age-induced GFR reduction, are there any other influence factors which increase serum CysC levels with aging? Can serum CysC level predict the risk of carotid atherosclerosis in healthy population? It is not clear.The goal of this study is to investigate the changing rule of serum CysC levels with aging and the factors influencing serum CysC, examine the ability of serum CysC as a predictor of carotid atherosclerosis, and the role of GFR.Methods Based on cluster sampling, we performed physical examinations, health questionnaire surveys, blood routine tests, urinalysis, and biochemical detections, and then selected 396 healthy people, aged 30 to 98, in Beijing. In which 252 patients completed 5-year follow-up. Serum CysC, high sensitivity C-reactive protein and fibrinogen were measured by immune nephelometry, high-sensitivity interleukin-6, thrombomodulin and D-dimer were measured by enzyme linked immunosorbent assay, tow-sample method measurement of GFR and the ultrasound measurement of cIMT and carotid plaque were performed.Results (1) Cross-sectional analysis showed:①When age increased, serum CysC levels, prevalence of plaque and carotid intima-media thickness increased, and GFR declined.②In subjects under 50 years old, serum CysC levels were higher in men than in women. There were no gender differences in prevalence of plaque, intima-media thickness and GFR.③Univariate analysis results:Serum CysC was positively correlated with age, waist-hip ratio, systolic blood pressure, creatinine, uric acid, urea and body mass index, and negatively correlated with GFR. Plaque was positively correlated with intima-media thickness, age, systolic blood pressure, pulse pressure, waist hip ratio, CysC, urea, creatinine, total cholesterol, triglycerides, low density lipoprotein cholesterol, high sensitive C-reactive protein, fibrinogen, thrombomodulin and IL-6, and negatively correlated with albumin and GFR. Intima-media thickness was positively correlated with plaque, systolic blood pressure, pulse pressure, BMI, waist to hip ratio, CysC, urea, creatinine, total cholesterol, triglycerides, low density lipoprotein cholesterol, high sensitive C-reactive protein, fibrinogen, thrombomodulin and IL-6, and negatively correlated with GFR and albumin.④Multiple linear regression analysis:age, GFR, uric acid and waist-to-hipratio were independent risk factors for serum CysC.⑤Logistic regression analysis:age was an independent risk factor for maxIMT, while age and waist-to-hipratio were independent risk factors for carotid plaque. (2) Five-year longitudinal follow-up showed:①Serum CysC increased with aging, and the increase was 0.012±0.022mg/L per year.②Compared to subjects without-plaques after examanition twice, the levels of CysC in subjects with-plaques after follow-up twice were higher. After adjusting for age, gender and weight, the differences between two groups disappeared. There was no difference among serum CysC divided by the change of intima-media thickness. (3) The area under the ROC curve and multiple linear regression analysis showed that:Using GFR 90ml/min·1.73m2 for the cut-off point to construct ROC curves, the AUC values for serum cystatin C level was higher than for serum creatinine level, P<0.01. The R2 (adjusted for age) improved from 0.375 to 0.587 for serum cystatin C level, and from 0.146 to 0.588 for serum creatinine level.Conclusions(1) Serum CysC levels increase with age. The increase in serum CysC with age is not merely affected by the decline of kidney function, age is an independent risk factor for serum CysC.(2) When age increases, carotid artery plaque and intima-media thickness increase, accompanied with elevated serum CysC levels and decreased GFR. However, it is age rather than GFR and serum CysC that is an independent risk factor for carotid atherosclerosis in healthy people. Thus, the serum CysC level can not predict the occurrence and extent of carotid atherosclerosis in healthy people.(3) When we evaluate renal function with serum CysC, we may include age to improve our forecast of renal function.