Osteoprotegerin Concentrations Relate Independently to Established Cardiovascular Disease in Rheumatoid Arthritis

Objective. We determined whether osteoprotegerin (OPG) concentrations are associated with established cardiovascular disease (CVD) among patients with rheumatoid arthritis (RA). Methods. OPG concentrations were measured by ELISA in 151 patients with RA (54 with CVD) and 62 age-matched control subjects without CVD. Established CVD was composed of documented ischemic heart disease, cerebrovascular disease, and peripheral artery disease. Results. In patients with RA, age, body mass index (BMI), rheumatoid factor (RF) positivity, anticyclic 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) ng/ml in controls and patients with RA who had CVD and those who did not, 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 patients with RA without CVD (p = 0.05) and in the latter compared to those with CVD (p = 0.03); the association of OPG concentrations with CVD among patients with RA also persisted after additional adjustment for RF and anti-CCP antibody positivity, and erosion status (p = 0.04). Conclusion. OPG concentrations are associated with disease severity and CVD prevalence in patients with RA. Whether consideration of OPG concentrations can improve CVD risk stratification in RA merits future longitudinal investigation.