Osteopontin is associated with increased arterial stiffness in rheumatoid arthritis

Rheumatoid arthritis (RA) patients are characterized by increased arterial stiffness, an independent predictor of cardiovascular risk. It has been suggested that osteopontin (OPN), a cytokine involved in RA pathogenesis, might have vascular effects. To study a possible relationship between OPN and arterial stiffness, aortic pulse wave velocity (PWV) was measured by tonometry in 69 patients (41 with RA, 28 with systemic sclerosis [SSc]) and 18 healthy controls. Plasma OPN levels, oxidative stress markers, and endothelin 1 (ET-1) were assessed. OPN levels were significantly ( P < 0.05) higher in RA (median 9.93, range 4.36-47.80 ng/mL) than in SSc (4.3, 2.1-19.7 ng/mL) or controls (5.2, 4.1-9.4 ng/mL). In RA patients, log-OPN was related to log-C-reactive protein (log-CRP) ( r = 0.30, P < 0.05), age ( r = 0.38, P < 0.01), Health Assessment Questionnaire (HAQ) ( r = 0.58, P < 0.0001), and inversely related to total cholesterol ( r= -0.33, P< 0.05) and apolipoprotein A (apoA) ( r= -0.58, P< 0.001), but not to oxidative stress markers and ET-1. PWV was similar in RA (median 8.1, range 4.7-16.4 m/s) and SSc (median 8.7, range 7.1-13.1 m/s), but significantly greater ( P < 0.01) than controls (median 7.5, range 4.1-10.4 m/s). Aortic PWV was related to log-OPN ( r = 0.40, P< 0.01) only in RA patients. It also was related to age ( r = 0.34, P< 0.05), mean blood pressure ( r = 0.44, P< 0.001), and HAQ ( r = 0.48, P< 0.001). In multiple regression analysis ( r2 = 0.36), including confounders, log-OPN remained a significant predictor ( P < 0.05) of PWV in RA. Elevated plasma OPN levels are associated with increased arterial stiffness in RA patients, suggesting that this protein might represent a bridge protein between inflammation and the consequent joint damage and cardiovascular risk in RA patients.