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 Table of Contents  
ORIGINAL ARTICLE
Year : 2012  |  Volume : 1  |  Issue : 1  |  Page : 16-19

Role of Cystatin-C in assessing the cardiovascular risk among overweight and obese individuals


1 Department of Biochemistry, JSS Medical College, JSS University, Mysore, Karnataka, India
2 Department of Community Medicine, JSS Medical College, JSS University, Mysore, Karnataka, India

Date of Web Publication21-May-2012

Correspondence Address:
Deepa Krishna
Department of ­Biochemistry, JSS Medical College, Sri Shivarathreeshwara Nagar, Mysore, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2278-344X.96414

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  Abstract 

Background: Cystatin C is a naturally occurring protease inhibitor that protects the host tissue from Cysteine protease Cathepsins, which is a pro-atherogenic factor. Cystatin C is a reliable marker of renal functions and its plasma concentration is dependent completely on Glomerular Filtration Rate, and has emerged as a biomarker of cardiovascular risk . The main objective of present study is to estimate the serum levels of Cystatin C in individuals with normal BMI, overweight and obese, aged between 20 and 39 years and to correlate the levels of serum Cystatin C with cardiovascular risk factors. Materials and Methods: The study population was taken from healthy volunteers of Mysore city, aged between 20 and 39 years of either sex. The study population was divided into three groups based on BMI. The sample size in each group was 20. Fasting serum sample was analyzed for glucose, HDL cholesterol, creatinine by enzymatic method and serum Cystatin C by immunoturbidimetric method using autoanalyser. Results: The serum Cystatin C levels was significantly increased in overweight and obese groups, P value <0.001. The mean serum Cystatin C levels in normal BMI group was 0.7 ± 0.03, in overweight group 0.91 ± 0.009 and in obese group was 1.15 ± 0.09. In the study, serum Cystatin C showed a positive correlation with serum total cholesterol ( r = 0.71), LDL cholesterol ( r = 0.69), total CHOL: HDL ( r = 0.77), HDL: LDL ( r = 0.75), serum glucose ( r = 0.61) and negative correlation with serum HDL ( r = -0.52). Conclusion: Serum Cystatin C can serve as a good predictive marker of preclinical cardiovascular disease and chronic kidney disease in overweight and obese individuals.

Keywords: Cystatin C, cardiovascular disease, obesity


How to cite this article:
Krishna D, Rahul M H, Suma M N, Vishwanath P, Devaki R N, Sudhir. Role of Cystatin-C in assessing the cardiovascular risk among overweight and obese individuals. Int J Health Allied Sci 2012;1:16-9

How to cite this URL:
Krishna D, Rahul M H, Suma M N, Vishwanath P, Devaki R N, Sudhir. Role of Cystatin-C in assessing the cardiovascular risk among overweight and obese individuals. Int J Health Allied Sci [serial online] 2012 [cited 2020 Jul 14];1:16-9. Available from: http://www.ijhas.in/text.asp?2012/1/1/16/96414


  Introduction Top


Obesity is an epidemic of the 21 st century and is a major causative factor for many other metabolic disorders and premature deaths in developing countries. This has been attributed to shifts in diet and lifestyle changes. The risk of cardiovascular disease, hypertension, hyperlipidemia, diabetes mellitus and certain cancers increase many folds in association with obesity. The WHO further projects that by 2015, approximately 2-3 billion adults will be overweight and more than 700 million will be obese. [1]

Human obesity is strongly associated with cardiovascular disease. An emerging theory suggests the contribution of factors secreted by adipose tissue to obesity-linked vascular alterations. [2] Cysteine protease Cathepsins is a proatherogenic factor which is produced by adipose tissue and is increased in obese subjects. [3] Cysteine proteases comprises a group of lysosomal proteolytic enzymes, which includes Cathepsins B, H, L, S and C that are involved in pathological processes such as inflammation, tumor invasion, breakdown of collagen and bone resorption. [4]

The activities of Cysteine proteases are controlled by naturally occurring inhibitory proteins such as Cystatins and α2 macroglobulin. These inhibitors function to protect host tissues from destructive proteolysis. Cystatin C is a non-glycated low-molecular weight basic protein that is a member of Cystatin super family of Cysteine protease inhibitors. The production of Cystatin C is regulated by housekeeping genes expressed in all nucleated cells. [5] Cystatin C has been proposed as a reliable marker of renal functions and its plasma concentration is dependent completely on Glomerular Filtration Rate.

In the recent years, Cystatin C has emerged as a potential marker for cardiovascular risk, and high concentration of Cystatin C is independently associated with cardiovascular risk factors such as age, sex, BMI, low HDL and smoking. [6]

With the increasing prevalence of obesity worldwide, there is an urgent need for better understanding of molecular mechanism linking obesity to metabolic and cardiovascular disease. Studies have shown that serum Cystatin C is consistently increased in obese individuals irrespective of their renal status; strongly suggest a role for adipose tissue as a contributor to circulating concentration of Cystatin C. Higher Cystatin C concentration is associated with increased cardiovascular risk and chronic kidney disease. Most of the previous studies are done on metabolic syndrome and diabetes mellitus, but in this study we are studying individuals who are at risk for future metabolic syndrome.

Hence in the present study, our goal was to determine whether the elevated Cystatin C concentration in overweight and obese individuals of age between 20 and 39 years could define a state of preclinical cardiovascular disease and chronic kidney disease.

Thereby we estimate the serum levels of Cystatin C in individuals with normal body mass index (BMI), overweight and obese, aged between 20 and 39 years and correlated the levels of serum Cystatin C with cardiovascular risk factors.


  Materials And Methods Top


Type of study - cross-sectional study.

Study design

The study population was taken from healthy volunteers of Mysore city, who are aged between 20 and 39 years of either sex. The study population was divided into three groups based on BMI as per the Health Ministry of India guidelines. [7] Individuals with BMI of less than 23 kg/m 2 were grouped into normal, those with BMI more than 23 kg/m 2 but less than 25 kg/m 2 were grouped in overweight and those with BMI more than 25 kg/m 2 as obese.

Each group contained sample size of 20. The sample size was estimated to be enough to detect a difference of 10% in serum cystatin C between three groups at 5% level of significance and 80% of power. Ethical clearance was taken from the Institutional Ethical Review Committee. A written informed consent was taken from the subjects.

Inclusion criteria

Healthy volunteers, aged between 20 and 39 years of either sex.

Exclusion criteria

Those with history of infections, diabetes, hypertension, chronic kidney disease and cancers were excluded from the studies.

Data regarding age, sex, occupation, diet, physical activity, BMI, blood pressure and others was collected in the form of questionnaires.

Four milliliters of fasting venous sample was collected from all the individuals in a plain vacutainer under aseptic precautions. Serum glucose was estimated by GOD-POD method, [8] Total cholesterol by CHOD-PAP method, [9] direct HDL cholesterol by immunoinhibition method, [10] LDL and VLDL was calculated by Friedwald's formula, [11] triglyceride by GPO-PAP methodology [12] and cystatin C by immunoturbidimetric method. [13] Cystatin C in the test sample binds to the specific polyclonal rabbit anti-Cystatin C antibody, which has been adsorbed to latex particles and agglutinates. The agglutination was detected as absorbance change at 546 nm. Serum ­creatinine was ­estimated by modified Jaffe's method. [14]

Statistical analysis

The results were expressed as mean ± standard deviation; P< 0.05 was considered statistically significant. Statistical analysis was performed using Epi info software and the tests used were Analysis of Variance [ANOVA] and Students' 't' test. To correlate the serum Cystatin C with cardiovascular risk factors, Pearson's correlation co-efficient was worked out.


  Results Top


The result of the present study is shown in [Table 1]. Group 1 represents individuals with BMI < 23 (Normal), Group 2 represent individuals with BMI 23-25 (Overweight), Group 3 with BMI >25 (Obese).
Table 1: Comparison of serum valves between the three study groups

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Data was expressed as mean ± standard deviation. Serum Cystatin C, total cholesterol, LDL cholesterol concentration and glucose levels was significantly increased in obese individuals when compared with non-obese control group. Cardiac risk markers like total cholesterol/HDL and HDL/LDL ratio was significantly increased in obese group. Serum creatinine did not show any significant changes among the three groups. Correlation between the serum Cystatin C and cardiovascular risk factors is shown in [Table 2]. [Figure 1], [Figure 2] and [Figure 3] shows a positive correlation of serum Cystatin C with the total cholesterol/ HDL ­ratio, HDL/LDL ratio and with serum glucose respectively.
Table 2: Correlation between the serum cystatin c and cardiovascular risk factors

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Figure 1: Correlation of serum cystatin C with total cholesterol/HDL ratio

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Figure 2: Correlation of serum cystatin C with HDL/LDL ratio

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Figure 3: Correlation of serum cystatin C with serum glucose

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  Discussion Top


Cystatin C, an endogenous inhibitor of Cathepsin proteases has emerged as a biomarker of cardiovascular risk and reduced renal function. Epidemiological studies indicate that serum cystatin C is increased in obesity. In the present study, serum Cystatin C is significantly increased in overweight and obese group when compared to normal weight individuals. These observations suggest that higher BMI is the main determinant of obesity - linked increase in serum cystatin C, and hence this study confirms the association between obesity and elevated cystatin C in humans. Serum cystatin C is consistently increased in obese individuals, irrespective of their renal status, which strongly suggests a role for adipose tissue as a contributor to circulating concentrations of this protein in obesity. In support of this hypothesis, the study conducted by Nadia Naour et al.[3] showed that cystatin C is highly expressed in human adipose tissue, equivalently in subcutaneous and omental fat depots, and that adipose tissue expression of cystatin C is increased in obesity. This increase could arise from enlarged adipocytes and macrophages, which express cystatin C mRNA and infiltrate the adipose tissue in obesity. [15] Based on its function as inhibitor of Cysteine proteases, cystatin C has the potential to influence pathological process relying, at least in part, on deregulation of Cathepsins. This includes atherosclerosis and other inflammatory-related disease. [16] Increased serum cystatin C might be part of regulatory mechanisms engaged to control the proatherogenic capacity of specific Cathepsins such as cathepsin S. [17]

In the present study, serum cystatin C showed a positive association with cardiovascular risk markers like LDL cholesterol, total cholesterol, HDL/LDL ratio and total cholesterol/HDL ratio. The study also showed a negative association with serum HDL levels. These results are in accordance with the study done by Parikh et al.[6] Interestingly, in the present study, serum glucose level increased as the cystatin C increased. Some researchers like Rishard et al. have also found such relation. The relation may need to be established further linking the molecular pathways and provides future directions for study. [18] Hence, this increased cystatin C could explain the risk of progression to pre-diabetes in these individuals.

In the recent years, several papers have confirmed the usefulness of cystatin C and its determination as a marker of early deterioration of GFR, being more sensitive than serum Creatinine. [19] Hence based on the results derived from the present study, it could be inferred that an increase in serum cystatin C could explain a state of pre-clinical kidney disease in the study population.


  Conclusion Top


With the increasing prevalence of obesity worldwide, there is an urgent need for better understanding of molecular mechanism linking obesity to metabolic and cardiovascular disease. In the present study, serum Cystatin C showed an increase with the increase in BMI of healthy individuals, which strongly suggests a role for adipose tissue as a contributor to circulating concentration of Cystatin C. Higher Cystatin C concentration could possibly be associated with increased cardiovascular risk and chronic kidney disease.

Hence serum Cystatin C could serve as a good predictive marker of preclinical cardiovascular disease and early chronic kidney disease in overweight and obese individuals of aged 20-39 years, who are prone for future development of metabolic syndrome and its complications.

 
  References Top

1.World Health Organization, Preventing chronic disease: A vital investment WHO global report, World Health Organization, Geneva, Switzerland, 2005. Available from: http://whqlibdoc.who.int/publications/2005/9241563001_eng.pdf [Last accessed on 2012 Mar 05].  Back to cited text no. 1
    
2.Dandona P, Aljada A, Chaudhuri A, Mohanty P, Garg R. Metabolic syndrome: A comprehensive perspective based on interactions between obesity, diabetes, and inflammation. Circulation 2005;111:1448-54.  Back to cited text no. 2
    
3.Naour N, Fellahi S, Renucci JF, Poitou C, Rouault C, Basdevant A, et al. Potential contribution of adipose tissue to elevated serum cystatin C in human obesity. Obesity 2009;17:2121-6.  Back to cited text no. 3
    
4.Bobek LA, Levine MJ. Cystatins-inhibitors of cysteine proteinases. Crit Rev Oral Biol Med 1992;3:307-32.  Back to cited text no. 4
    
5.Taglieri N, Koenig W, Kaski JC. Cystatin C and cardiovascular risk. Clin Chem 2009;55:1932-43.  Back to cited text no. 5
    
6.Parikh NI, Hwang SJ, Yang Q, Larson MG, Guo CY, Robins SJ, et al. Clinical correlates and heritability of cystatin C (from the Framingham Offspring Study). Am J Cardiol 2008;102:1194-8.  Back to cited text no. 6
    
7.India reworks obesity guidelines, BMI lowered. Available from: http://www.igoverntment.in/site/India-reworks-obesity-guidelines-BMI-lowered/ 11/26/2008. [Last accessed on 2011 Mar 10].  Back to cited text no. 7
    
8.Trinder P. Quantitative determination of glucose using GOD-PAP method. Ann Clin Biochem 1969;6:24-7.  Back to cited text no. 8
    
9.Allain CC, Poon LS, Chan CS, Richmond W, Fu PC. Enzymatic determination of total serum cholesterol. Clin Chem 1974;20:470-5.  Back to cited text no. 9
    
10.Sugiuchi H, Uji Y, Okabe H, Irie T, Uekama K, Kayahara N, et al. Direct measurement of high-density lipoprotein cholesterol in serum with polyethylene glycol-modified enzymes and sulfated alpha-cyclodextrin. Clin Chem 1995;41:717-23.  Back to cited text no. 10
    
11.Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499-502.  Back to cited text no. 11
    
12.Schettler G, Nussel E, Jacob NJ. Estimation of triglycerides by GPO-PAP method. Arch Biochem Biophys 1960;88:250-5.  Back to cited text no. 12
    
13.Kyhse-Andersen J, Schmidt C, Nordin G, Andersson B, Nilsson-Ehle P, Lindström V, et al. Serum cystatin C, determined by a rapid, automated particle-enhanced turbidimetric method, is a better marker than serum creatinine for glomerular filtration rate. Clin Chem 1994;40:1921-6.  Back to cited text no. 13
    
14.Bowers LD. Kinetic serum creatinine assays I. The role of various factors in determining specificity. Clin Chem 1980;26:551-4.  Back to cited text no. 14
    
15.Cancello R, Henegar C, Viguerie N, Taleb S, Poitou C, Rouault C, et al. Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes 2005;54:2277-86.  Back to cited text no. 15
    
16.Chapman HA, Riese RJ, Shi GP. Emerging roles for cysteine proteases in human biology. Annu Rev Physiol 1997;59:63-88.  Back to cited text no. 16
    
17.Sukhova GK, Shi GP, Simon DI, Chapman HA, Libby P. Expression of the elastolytic cathepsins S and K in human atheroma and regulation of their production in smooth muscle cells. J Clin Invest 1998;102:576-83.  Back to cited text no. 17
    
18.Donahue RP, Stranges S, Rejman K, Rafalson LB, Dmochowski J, Trevisan M. Elevated cystatin C concentration and progression to pre-diabetes: The Western New York study. Diabetes Care 2007;30:1724-9.  Back to cited text no. 18
    
19.Jung K, Jung M. Cystatin C: A promising marker of glomerular filtration rate to replace creatinine. Nephron 1995;70:370-1.  Back to cited text no. 19
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2]



 

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