Background/Purpose: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased cardiovascular risks. Cathepsin S, a cysteine protease implicated in intracellular and extracellular proteolysis, and its endogenous inhibitor cystatin C has been both associated with increased cardiovascular mortality in general population. 

Objective. To assess if serum cathepsin S and cystatin C, two novel markers of cardiovascular disease risk are associated with subclinical carotid atherosclerosis in RA patients. 

Methods: Serum cystatin C and cathepsin S levels, ultrasound carotid intima-media thickness (cIMT) and carotid plaques were assessed in a cross-sectional study involving 178 RA patients.Multivariate regression analysis was assessed to study the relationship between cathepsin S and cystatin C serum levels and cardiovascular risk factors and disease related data.

Results: Mean cIMT was 0.670 ± 0.143 mm, and 66 patients (37%) had carotid plaques in the carotid ultrasound assessment. Both cystatin C and cathepsin S were significantly associated with hypertension, diabetes and dyslipidemia. Cathepsin S was inversely related with male gender whereas cystatin was strongly associated with age. Regarding RA related data; cathepsin S was associated with disease duration and cystatin C was positively related with higher levels of ESR. Neither positive rheumatoid factor nor prednisone use were associated with cystatin C or cathepsin S. A trend for lower levels of cystatin C was observed in patients undergoing anti-TNF-alpha therapy (log beta coef. -0.20 (-0.44-0.04), p=0.09). An association between disease activity scores with higher levels of cystatin C, but not with cathepsin S, was found. Cystatin C levels were associated with cIMT in the subgroup of patients included in the higher quartile of cIMT (OR 1.31, 95%CI [1.00-1.72], p=0.04) after adjusting for traditional cardiovascular risk factors, age and sex. An association between serum cystatin C levels and carotid plaques was also found in the univariate analysis (OR 1.37, 95%CI [1.06-1.76], p=0.02). However, this significant association was lost after adjusting for traditional cardiovascular risk factors and age. Cathepsin S was not associated with cIMT or carotid plaques.

Conclusion: High cystatin C serum levels identify a subgroup of RA patients with a high risk of subclinical atherosclerotic disease.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-cathepsin-s-and-cystatin-c-relation-with-carotid-subclinical-atheromatosis-in-rheumatoid-arthritis-patients/