Background Osteoprotegerin (OPG) may participate in the pathophysiology of rheumatoid arthritis (RA) (1). Recently reported evidence further supports a potential involvement of OPG in endothelial activation and subclinical atherosclerosis in RA (2).
Objectives We determined whether osteoprotegerin (OPG) concentrations are independently related to established cardiovascular disease (CVD) amongst patients with rheumatoid arthritis.
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. Relationships were assessed in mixed regression models.
Results In RA patients, age, rheumatoid factor and anti-cyclic citrullinated peptide antibody positivity, joint erosion status and body mass index were associated with OPG concentrations (partial R (P)=0.175 (0.03), 0.323 (<0.0001), 0.217 (0.008), 0.159 (0.05) and -0.277 (0.0009)), 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) in controls and RA patients without and with CVD, respectively (P=0.0002). In potential confounding or/and mediating characteristic adjusted analysis, OPG concentrations remained lower in controls compared to RA patients without CVD (P=0.04) and in the latter compared to those with CVD (P=0.03). OPG concentrations related independently to those of angiopoietin 2 in RA patients with but not without CVD (partial R (P)=0.537 (0.001) and 0.060 (0.7)).
Conclusions OPG concentrations are associated with disease severity and CVD prevalence in RA patients. OPG may contribute to the link between RA severity and enhanced cardiovascular risk.
Ziolkowska M et al. High levels of osteoprotegerin and soluble receptor activator of nuclear factor κB ligand and their normalization alter anti-tumor necrosis factor α treatment. Arthritis Rheum 2001;46:1744-53.
Dessein PH et al. Independent relationship of osteoprotegerin concentrations with endothelial activation and carotid atherosclerosis in patients with severe rheumatoid arthritis. J Rheumatol 2014 (in press).
Acknowledgements This study was supported by grants from “Fondo de Investigaciones Sanitarias” 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). Research performed by Patrick Dessein was supported by the South African Medical Research Council (grant number MRC2008_DES) and the National Research Foundation.
Disclosure of Interest None declared