LAUSR

Background monocytes are largely recognized as drivers of the atherosclerosis development, the leading determinant of cardiovascular (CV) morbidity in rheumatoid arthritis (RA). Far from being a unique population, functionally and phenotypically subpopulations can be distinguished, although their relevance to CV disease is uncertain. Recently, the expression of angiotensin-converting enzyme (ACE) expression has been described, with some heterogeneity being observed across monocyte subsets. However, although previously linked to blood pressure control, the significance of ACE expression on monocytes remains obscure. Objectives to evaluate whether monocyte subsets and ACE expression were associated with surrogates of CV subclinical disease in very early RA patients. Methods patients were recruited upon early referral to the rheumatology department. All patients were untreated at the time of sampling. The frequency of classical (CD14+CD16-), intermediate (CD14+CD16+) and non-classical (CD14lowCD16+) monocyte subpopulations and ACE expression were assessed by flow cytometry in peripheral blood. Plaque occurrence, cIMT and stiffness parameters were analyzed by Doppler ultrasound in internal carotid, middle cerebral and basilar arteries. Results 53 patients were recruited, 47 fulfilling 2010 ACR/EULAR classification criteria for RA (36 women, 26 FR+ and 26 ACPA+) and 6 fulfilling criteria for Clinically Suspect Arthralgia (CSA) (6 women, 3 RF+ and 2 ACPA+). Non-classical and intermediate monocytes were positively associated with cIMT (r=0.413, p=0.005 and r=0.353, p=0.018, respectively), as well as with pulsatility (r=0.332, p=0.026 and r=0.323, p=0.030) and resistivity indices (r=0.286, p=0.050 and r=0.277, p=0.045) at the left internal carotid artery. Expansion of CD16+ monocytes was not associated with disease activity, measured as DAS28 or SDAI (all p>0.050), but frequency of intermediate monocytes paralleled duration of the symptoms (r=0.324, p=0.020). ACE expression was higher in CD16+ monocyte subsets than in their classical counterparts. ACE expression was not associated with blood pressure, individual traditional CV risk factors, body mass index nor with mSCORE (all p>0.050). ACE expression on intermediate and classical monocytes was correlated with cIMT (r=0.382, p=0.010 and r=0.349, p=0.019, respectively). Moreover, ACE expression in all monocyte subsets was strongly associated with resistivity and pulsatility indices at the internal carotid artery (all p<0.010). Conclusion the expansion of CD16+ monocyte subsets and the ACE expression are associated with arterial wall thickening and vascular functionality in treatment-naïve RA patients, hence suggesting a very early role for monocyte traits in this scenario. None declared