Abstract
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 (r(2) = 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.
Highlights
Rheumatoid arthritis (RA) is a chronic progressive inflammatory disease, characterized by synovial inflammation and hyperplasia, leading to progressive cartilage and bone destruction [1]
OPN is rapidly emerging as a major player in both physiological and pathological processes throughout the body, as is evident from data that has emerged from studies conducted over the past
Literature showed that OPN is involved in the evolution and progression of multiple systemic diseases [36]; it has been linked to the aethiopathogenesis of breast cancer [37], osteoporosis, multiple sclerosis [21,38], inflammatory bowel diseases [22], psoriasis [20,25], and lupus erythematosus systemicus [24,39]
Summary
Rheumatoid arthritis (RA) is a chronic progressive inflammatory disease, characterized by synovial inflammation and hyperplasia, leading to progressive cartilage and bone destruction [1]. PWV is a vascular parameter of important clinical significance since it has been demonstrated to be an independent predictor of cardiovascular events both in high-risk patients and in the general population [12]. Increased arterial stiffness was demonstrated in RA patients at the abdominal aorta [13] and carotid site [14], and as elevated aortic PWV [15]. The latter alteration was related to C-reactive protein (CRP) levels, and was reversible after anti-TNF therapy [15,16]; but it was associated with risk factors such as age, blood pressure, and abdominal obesity [17]. Aortic PWV was related to paraarticular trabecular bone loss at the ultradistal radius [18]
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