Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Cystatin C, Renal Function and Atherosclerosis in Rheumatoid Arthritis.

Lertnawapan2,  Ratchaya, Bian2,  Aihua, Rho2,  Yong Hee, Kawai2,  Vivian, Raggi1,  Paolo, Oeser2,  Annette, Solus2,  Joseph

Emory University, Atlanta, GA
Vanderbilt University, Nashville, Nashville, TN

Purpose:

Cystatin C, a novel marker of renal function, is a more accurate measure of glomerular filtration rate (GFR) than serum creatinine. Cystatin C is a cysteine protease inhibitor and its serum concentrations are associated with inflammation, insulin resistance, and cardiovascular risk. Patients with rheumatoid arthritis (RA) frequently have inflammation, insulin resistance, subclinical renal dysfunction and premature atherosclerosis. We examined the hypothesis that cystatin C is increased in RA, and associated with inflammation, insulin resistance and coronary artery atherosclerosis.

Methods:

We measured serum cystatin C, creatinine, C-reactive protein (CRP), tumor necrosis factor-a (TNF-a), and interleukin-6 (IL-6) concentrations in serum samples from 167 patients with RA and 91 control subjects without inflammatory rheumatic disease. Coronary calcium score, homeostasis model assessment (HOMA) index, Modified Diet in Renal Disease formula-estimated GFR (MDRD-eGFR) and clinical parameters including RA disease activity (DAS28) were also measured. We compared cystatin C concentrations in patients with RA and controls using a multivariable regression analysis that adjusted for demographic variables and renal function (MDRD-eGFR). In patients with RA we assessed the relationship between cystatin C and measures of inflammation, Framingham risk score (FRS) and coronary-artery calcium score (CACS) using Spearman correlation and multivariable regression.

Results:

Concentrations of cystatin C were significantly higher in patients with RA (median (IQR): 1.16 (0.99–1.35) mg/L) than controls (1.01 (0.90–1.19) mg/L), (adjusted P<0.001). Serum creatinine concentrations (P=0.62) and MDRD-eGFR (P=0.53) did not differ significantly among RA and control groups. In patients with RA, cystatin C concentrations were significantly positively correlated with creatinine (rho=0.43, P<0.001) and significantly inversely correlated with MDRD-eGFR (rho=-0.43, P<0.001). In RA cystatin C was positively correlated with ESR (rho=0.26, P<0.001), CRP (rho=0.20, P=0.01), DAS28 (rho=0.19, P=0.006), FRS (rho=0.44, P<0.001) and TNF-a (rho=0.20, P=0.01), but not with IL-6, or HOMA (both P>0.05) (Table). After adjustment for age, race and sex, only associations with ESR, CRP, DAS28 and FRS retained statistical significance. Cystatin C also correlated with CACS (P<0.001) in RA but this was not significant after adjustment for age, race, sex and FRS (P=0.67).

Conclusions:

Cystatin C concentrations are higher in patients with RA than compared to subjects without RA; this may reflect undetected subclinical renal dysfunction and inflammation. Cystatin C provides information regarding the risk of atherosclerosis in RA, but this is not independent of the information provided by conventional cardiovascular risk factors.

Table. Relationship between Cystatin C and Cardiovascular Risk Factors, Inflammation and Coronary Calcium Score in RA

  Cystatin C 
FactorRho** (r)Unadjusted p-valueAdjusted p-value*
Age0.44<0.001
Homocysteine0.49<0.001<0.001
HOMA index0.090.2610.15
Framingham score0.44<0.0010.05
DAS280.190.0130.006
ESR0.260.001<0.001
CRP0.200.010.009
TNF-a0.200.0110.11
IL-60.100.1850.322
Coronary calcium score0.32<0.0010.674
*Adjusted p-values are all adjusted for age, race and sex, except for coronary calcium score that is additionally adjusted for Framingham risk score. Multivariable linear regression was used in Adjusted p-value.**Univariate Spearman correlation coefficient (n=167)HOMA Index=Homeostasis Model Assessment Index; DAS28=Disease Activity Score 28-joint assessment; ESR=Erythrocyte Sediment Rate; CRP=C-Reactive Protein; TNF-a=Tumor Necrosis Factor-a; IL-6=Interleukin-6

To cite this abstract, please use the following information:
Lertnawapan, Ratchaya, Bian, Aihua, Rho, Yong Hee, Kawai, Vivian, Raggi, Paolo, Oeser, Annette, et al; Cystatin C, Renal Function and Atherosclerosis in Rheumatoid Arthritis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1023
DOI: 10.1002/art.28790

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