Aim: Osteopontin (OPN) is a pleiotropic cytokine involved in the regulation of mineralization, expressed in bone and kidney, whose levels are elevated during and inflammation. We evaluated the possible relationship between OPN and arterial stiffness in patients with rheumatoid arthritis (RA).

Methods: In 40 RA patients (56±5 years, 32 females) and 40 age and sex-matched healthy volunteers, applanation tonometry (Sphygmocor®) was applied for measuring augmentation index (AIx) and carotid to femoral pulse wave velocity (PWV). Endothelium-dependent (flow-mediated dilation, FMD) and independent (sublingual glycerol trinitrate, GTN, 25 μg) vasodilation were assessed by ultrasound and computerized analysis of brachial artery diameter changes. Plasma levels of OPN and C-reactive protein were also evaluated

Results: OPN levels resulted higher in RA patients than in healthy controls (13.3±9.8 vs 5.4±3.1 ng/ml; p<0.05). PWV (8.7±2.5 vs 7.6± m/s; p<0.05), AIx (30.8±8.3 vs 26.1±7.9 units; p<0.05) and FMD (6.1±.3.2 vs 7.2±3.2%; p<0.05) were significantly different in RA patients than controls In RA patients, log-transformed OPN was related to PWV(r=0.41; p<0.01), but not to AIx, FMD or response to GTN. Log-OPN levels correlated significantly also with age (r=0.37; P<0.01), and log CRP (r=0.31; p<0.05). In multiple regression analysis (r²=0.35) including age, mean blood pressure and logCRP, logOPN remained a significant predictor of aortic PWV (p<0.05).

Conclusions: RA patients are characterized by elevated OPN levels, increased arterial stiffness and endothelial dysfunction. The selective, independent relationship between OPN levels and aortic PWV suggests that OPN might represent an important marker/mechanisms for increased arterial stiffness in RA patients.