Abstract
Increased cardiovascular (CV) morbidity and mortality have been found in rheumatoid arthritis (RA). Tumour necrosis factor α (TNF-α) inhibitors may improve vascular function. In the first part of this study, we determined microcirculation during postoocclusive reactive hyperemia (PORH) representing endothelial function. In a nonselected population (n = 46) we measured flow-mediated vasodilation (FMD) of the brachial artery and laser Doppler flow (LDF) by ultrasound. Among LDF parameters, we determined TH1 (time to half before hyperemia), TH2 (time to half after hyperemia), Tmax (time to maximum) and total hyperemic area (AH). We measured von Willebrand antigen (vWF:Ag) by ELISA. In the second part of the study, we assessed the effects of adalimumab treatment on microcirculatory parameters in 8 early RA patients at 0, 2, 4, 8 and 12 weeks. We found significant positive correlations between FMD and LDF Tmax (R = 0.456, p = 0.002), FMD and TH2 (R = 0.435, p = 0.004), and negative correlation between vWF:Ag and Tmax (R = − 0.4, p = 0.009) and between vWF:Ag and TH2 (R = − 0.446, p = 0.003). Upon adalimumab therapy in early RA, TH2 times improved in comparison to baseline (TH2baseline = 26.9 s vs. TH24weeks = 34.7 s, p = 0,032), and this effect prolonged until the end of treatment (TH28weeks = 40.5, p = 0.026; TH212weeks = 32.1, p = 0.013). After 8 weeks of treatment, significant improvement was found in AHa (AHbaseline = 1599 Perfusion Units [PU] vs. AH8weeks = 2724 PU, p = 0.045). The PORH test carried out with LDF is a sensitive option to measure endothelial dysfunction. TH1 and TH2 may be acceptable and reproducible markers. In our pilot study, treatment with adalimumab exerted favorable effects on disease activity, endothelial dysfunction and microcirculation in early RA patients.
Highlights
Increased cardiovascular morbidity and mortality have been associated with rheumatoid arthritis (RA) and other inflammatory arthritides [1,2,3,4,5,6,7,8]
Simultaneous assessment of brachial artery FMD and laser Doppler postocclusive reactive hyperemia (PORH) curves After PORH test carried out in healthy individuals representing the general population (n = 46), FMD as a measure of macrovascular endothelial function were assessed on the forearm and the microcirculatory laser Doppler flowmetry (LDF) PORH parameters detected by the primary probe were correlated with the reference FMD methods
Microvascular endothelial function characterized by TH2 times, as the most reliable indicator, significantly improved in comparison to baseline as early as by week 4 (p = 0.032), and this effect was sustained until the end
Summary
Increased cardiovascular morbidity and mortality have been associated with rheumatoid arthritis (RA) and other inflammatory arthritides [1,2,3,4,5,6,7,8]. Pilot part of the study we longitudinally assessed the effects of the tumour necrosis factor α (TNFα) inhibitor adalimumab on microcirculatory (LDF), macrovascular (brachial artery FMD) function, as well as vWF:Ag levels (biomarker of endothelial activation) in patients with early, untreated RA. Simultaneous assessment of brachial artery FMD and laser Doppler PORH curves After PORH test carried out in healthy individuals representing the general population (n = 46), FMD as a measure of macrovascular endothelial function were assessed on the forearm and the microcirculatory LDF PORH parameters detected by the primary probe were correlated with the reference FMD methods. After 8 weeks of treatment, significant improvement could be observed in AH (p = 0.045) and in AUC1min (p = 0.019) (Table 3) The latter paramaters may not reflect endothelial function as shown in our previous study. VWF:Ag levels did not show significant decreases upon anti-TNF therapy (Fig. 4)
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