ADALIMUMAB IMPROVES ENDOTHELIAL FUNCTION AND MICROCIRCULATION IN RHEUMATOID ARTHRITIS AS DETERMINED BY SIMULTANEOUS ASSESSMENT OF BRACHIAL ARTERY FLOW-MEDIATED VASODILATION AND LASER DOPPLER FLOWMETRY

Background: Increased cardiovascular morbidity has become a leading cause of mortality in rheumatoid arthritis (RA). Impaired endothelial-dependent, flow-mediated vasodilation (FMD) of the brachial artery has been documented by various groups. Anti-TNF agents have been found to improve FMD in RA. However, there have been neither reports on laser doppler assessments in RA nor the effects of any biologics on laser doppler curves. Objectives: Here we simultaneously assessed brachial artery FMD and laser doppler curves before and after 12 weeks of adalimumab (ADA) therapy. Methods: First, we determined microcirculatory parameters during postoocclusive reactive hyperemia (PORH) representing endothelial function in a non-selected population of RA patients (n=46). We assessed FMD of the brachial artery using ultrasound and, simultaneously, laser Doppler PORH curves were recorded. Plasma von Willebrand Factor (vWF) levels were also determined in all patients. Then we assessed the effects of ADA treatment (40mg sc, biweekly) on microcirculatory parameters in 8 patients with early RA (disease duration <1 year). Vascular assessment was performed at baseline and then 2, 4, 8 and 12 weeks after the initiation of ADA treatment. Results: After the comparison of FMD values and vWF levels with laser doppler PORH curves, significant positive correlations were found between FMD and time to max (Tmax, R=0,456, p=0,002), FMD and halftime of deceleration (TH2, R=0,435, p=0,004), and significant negative correlations were detected between vWF and Tmax (R=-0,4, p=0,009) and between vWF and TH2 (R=-0,446, p=0,003). ADA significantly decreased CRP levels (p=0.04) and DAS28 (p<0.0001). Endothelial function characterized by TH2 times improved in comparison to baseline (34.7 sec vs 26.9 sec; p=0,03), and this effect was prolonged until 8 weeks (40.5 sec; p=0,026) and 12 weeks of treatment (32.1 sec, p=0,013). After 8 weeks of treatment, significant improvement was observed in hyperemic area (AHbaseline=1599 PUxs vs. AH8weeks=2724 PUxs, p=0,045), in 1 minute postocclusion area (APObaseline=1469 PUxs vs. APO8weeks=2462 PUxs, p=0,019) and in average perfusion until peak (PtoMaxbaseline=32,2 PU vs. PtoMax8weeks=46,33, p=0,035). Conclusions: The PORH test carried out with laser Doppler is a sensitive option to measure endothelial dysfunction, but only the time course of the hyperemia may be accepted as a reliable parameter. Both brachial artery FMD and laser doppler PORH assessments are useful to detect micro- and macrocirculatory endothelial dysfunction in RA patients. Treatment of early RA patients with ADA exerted favorable effects on disease activity, endothelial dysfunction and microcirculation. Early anti-TNF therapy may have important relevance for the prevention and management of vascular comorbidity in RA. Disclosure of Interest: None DeclaredCitation: Annals of the Rheumatic Diseases, volume 70, supplement 3, year 2011, page 598Session: Rheumatoid arthritis – comorbidity and clinical aspects (Poster Presentations )