Serum osteoprotegerin is increased and independently associated with coronary-artery atherosclerosis in patients with rheumatoid arthritis

Abstract

Osteoprotegerin (OPG), a soluble decoy receptor for receptor activator of nuclear factor kappaB ligand, is implicated in the pathogenesis of atherosclerosis. Patients with rheumatoid arthritis (RA) have inflammation and increased atherosclerosis. We examined the hypothesis that OPG concentrations are increased in patients with RA and are associated with coronary-artery atherosclerosis. Serum OPG concentrations were measured by ELISA and coronary-artery calcification by electron-beam computer tomography in 157 patients with RA and 87 control subjects. OPG concentrations were higher in patients with long-standing RA (n=67) [median (interquartile range)]: [1895 (1337-2847) pg/mL, and early RA (n=90): [1340 (1021-1652) pg/mL, than controls 1068 (692-1434) pg/mL; (p<0.001)]. In patients with RA, OPG concentrations were associated with erythrocyte sedimentation rate (p<0.001), homocysteine (p=0.001), disease duration (p=0.02), coronary calcium score (p=0.03), and cumulative dose of corticosteroids (p=0.04) after adjustment for age and sex. In patients with long-standing RA, OPG was associated with coronary-artery calcification independently of cardiovascular risk factors and disease activity [OR for every increase in 500 pg/mL of OPG=2.22 (1.43-3.34), p<0.001]. In conclusion, OPG concentrations are increased in patients with RA and are associated with inflammation. In patients with long-standing disease, OPG is independently associated with coronary-artery calcification.

Figure 1

Association between serum OPG and coronary artery calcification in patients with RA OPG concentrations (means and 95% C.I.) among patients and controls with no, low or severe calcification. P-value for trend=0.05 among patients with early RA, p=0.003 among patients with long-standing RA, and P=0.16 among control subjects.

FIGURE 2

Association between serum OPG and coronary calcification in patients with RA^{† †} Applying proportional odds model to calculate the odds ratio and 95%CI for every 500 pg/ml increase of osteoprotegerin. * Adjusted for age and sex. ** Adjusted for age, race, sex, homocysteine, cholesterol profile (HDL cholesterol, LDL cholesterol, triglycerides, lipoprotein a), hypertension, diabetes, and pack-years of smoking.