Background Osteoprotegerin (OPG) is implicated in the pathogenesis of atherosclerosis. Recent studies have shown that arterial stiffness, carotid intima-media thickness (CIMT) and OPG are independent risk factors of cardiovascular (CV) disease. Serum OPG levels are elevated in patients with rheumatoid arthritis (RA) and decrease after anti-TNF therapy. RA patients have chronic inflammation and increased atherosclerosis. The relationship between OPG concentrations and accelerated atherosclerosis in patients with RA has not been established. Chronic inflammation may impair vascular function and lead to and increase of CIMT, arterial stiffness, serum OPG levels, an important determinants of CV risk.
Objectives In present study we aimed to establish whether serum OPG levels, CIMT, aortic stiffness are increased in RA patients and to investigate the relationship between these parameters and clinical features.
Methods We identified RA patients and healthy controls (HC) aged between 18 and 60 years. We excluded patients and HC with CV risk factors, such as hypertension, diabetes, hypercholesterolaemia or obesity. Sixty(14 male and 46 female) RA patients with mean age of 40.8±8.3 years and sex and age matched 30 (7 male and 23 female) HC with mean age of 40.8±7.9 years were enrolled. Median disease duration was 6 years (1-20). Serum levels of OPG were measured by commercially available ELISA kits (RayBiotech Human OPG). Aortic stiffness was measured wiyh high resolution echocardiography. High resolution doppler ultrasonography was used to measure mean and maximal common carotid artery intima-media wall thickness (CIMT).
Results Serum OPG levels in RA patients were statistically higher than those in HC (60.1 vs 30 pg/ml, respectively, p<0.001). Mean and maximal CIMT were significantly higher in RA patients compared with HC (0.59 vs 0.53 mm, p=0.007, respectively and 0.68 vs 0.58 mm, p<0.001, respectively). Although aortic stiffness in RA patients was higher than that in HC (5.6 vs 4.6, respectively, p=0.114), the difference did not reach statistically significance. In RA patients CIMT was significantly correlated with aortic stiffness (r=0.283, p=0.024). In RA patients and HC serum OPG levels were not correlated with CIMT and aortic stiffness (p>0.05). Moreover, age in RA patients was positively associated with serum OPG levels (r=0.305, p=0.018), CIMT (r=0.614, p<0.001) and aortic stiffness (r=0.266, p=0.04). Aortic stiffness in male RA patients was significantly higher compared with female patients (7.1 vs 5.1, respevtively, p=0.013).
Conclusions In this study RA patients had higher OPG levels and CIMT compared with HC. Furthermore age and sex in RA patients was significantly associated with CV risk factors (including OPG, CIMT and aortic stiffness). Further prospective trials with large sample size are needed to establish relationship between aortic stiffness and cardiovascular risk in RA patients.
Asanuma Y, et al. Atherosclerosis 2007; 195: 135-141.
Sliem H, et al. J Cardiolvasc Dis Res 2010; 1: 110-5.
Kumeda Y, et al. Arthritis Rheum 2002; 46: 1489-1497.
Disclosure of Interest None Declared