Background/Purpose: We determined whether osteoprotegerin (OPG) concentrations are associated with established cardiovascular disease (CVD) amongst patients with rheumatoid arthritis (RA). 

Methods: OPG concentrations were measured by an enzyme-linked immunosorbant assay in 151 (54 with CVD) RA patients and 62 age and sex matched control subjects without CVD.  Concentrations of the endothelial activation marker angiopoietin 2 were also evaluated in a subgroup of 85 RA participants.  

Results: In RA patients, age, body mass index (BMI), rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody positivity, and joint erosion status were associated with OPG concentrations (partial R (p)=0.175 (0.03), -0.277 (0.0009), 0.323 (<0.0001), 0.217 (0.008) and 0.159 (0.05)), respectively.  Median (interquartile range) OPG concentrations increased from 6.38 (3.46-9.31) to 7.07 (5.04-10.65) and 8.64 (6.00-11.52) pmol/l in controls and RA patients without and with CVD, respectively (p=0.0002).  Upon adjustment for age, sex, traditional risk factors and BMI in mixed regression models, OPG concentrations remained lower in controls compared to RA patients without CVD (p=0.05) and in the latter compared to those with CVD (p=0.03); the association of OPG concentrations with CVD amongst RA patients also persisted after additional adjustment for RF and anti-CCP antibody positivity, and erosion status (p=0.04).  OPG concentrations related independently to those of angiopoietin 2 in RA patients with but not without CVD (partial R (p)=0.545 (0.003) and 0.076 (0.6)). 

Conclusion: OPG concentrations are associated with disease severity and CVD prevalence in RA patients.  Whether consideration of OPG concentrations can improve CVD risk stratification in RA merits future longitudinal investigation.

This study was supported by European Union FEDER funds and “Fondo de Investigación Sanitaria” (grants PI06/0024, PS09/00748 and PI12/00060) (Spain). This work was also partially supported by RETICS Program, RD08/0075 and RD12/0009/0013 (RIER) from “Instituto de Salud Carlos III” (ISCIII) (Spain). RLM is a recipient of a Sara Borrell postdoctoral fellowship from the “Instituto de Salud Carlos III” at the Spanish Ministry of Health (Spain) (CD12/00425). FG and BU are supported by funds from the RETICS Program (RIER) (RD12/0009/0013). Research performed by Patrick Dessein was supported by the South African Medical Research Council (grant number MRC2008_DES) and the National Research Foundation.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/osteprotegerin-concentrations-are-independently-related-to-established-cardiovascular-disease-in-rheumatoid-arthritis/