Independent relationship of osteoprotegerin concentrations with endothelial activation and carotid atherosclerosis in patients with severe rheumatoid arthritis.
OBJECTIVE
Osteoprotegerin (OPG) may contribute to the link between systemic inflammation and increased cardiovascular risk. We investigated the relationship of OPG concentrations with endothelial activation and carotid atherosclerosis in rheumatoid arthritis (RA).


METHODS
OPG concentrations and those of endothelial activation molecules were measured by using ELISA in 34 patients who were treated with infliximab (IFX), both immediately before and after an IFX infusion. Carotid intima-media thickness (CIMT) and plaque were determined by ultrasound in 27 of the study participants.


RESULTS
Median (interquartile range) OPG concentrations decreased from 4.8 pmol/l (2.8-6.5) to 4.4 pmol/l (2.9-6.1; p = 0.04) upon IFX infusion. Baseline OPG concentrations were inversely associated with those of total and low-density lipoprotein (LDL) cholesterol (partial R = -0.50, p = 0.004, and R = -0.48, p = 0.007, respectively). Prior to IFX administration, OPG concentrations were associated with those of intercellular adhesion molecule (ICAM)-1 (partial R = 0.34, p = 0.05), CIMT (partial R = 0.51 to 0.52, p < 0.009), and plaque (OR = 1.52, 95% CI 1.01-2.29 to OR = 1.61, 95% CI 1.03-2.51; p < 0.04), independent of conventional risk factors and C-reactive protein concentrations or disease activity. Except for the OPG concentrations-plaque association (p = 0.09), these relationships remained significant subsequent to IFX administration (p < 0.05). Reductions in OPG levels related to those in vascular cell adhesion molecule (VCAM)-1 concentrations (partial R = 0.35, p = 0.04) and had borderline significance (p = 0.09) with those in ICAM-1 (partial R = 0.29) concentrations.


CONCLUSIONS
OPG concentrations are independently associated with endothelial activation and carotid atherosclerosis in RA. Reductions in OPG concentrations upon IFX administration are associated with decreased endothelial activation. OPG may be involved in increased cardiovascular disease risk and may improve its stratification in patients with RA.
From the Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, IFIMAV, Santander; Cardiology Division, Hospital Xeral-Calde, Lugo; Rheumatology Division, Hospital Xeral-Calde, Lugo; Department of Epidemiology and Computational Biology, School of Medicine, University of Cantabria, IFIMAV, and CIBER Epidemiología y Salud Pública (CIBERESP), Santander, Spain.
Patrick H
PH
Dessein
Raquel
R
López-Mejias
Carlos
C
González-Juanatey
Fernanda
F
Genre
José A
JA
Miranda-Filloy
Javier
J
Llorca
Miguel A
MA
González-Gay
D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D050197:Atherosclerosis / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D002340:Carotid Artery Diseases / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood*
D053244:Osteoprotegerin
ENDOTHELIAL ACTIVATION ATHEROSCLEROSIS; OSTEOPROTEGERIN; RHEUMATOID ARTHRITIS; TNF-α BLOCKADE