A prospective, longitudinal monocentric study on laser Doppler imaging of microcirculation: comparison with macrovascular pathophysiology and effect of adalimumab treatment in early rheumatoid arthritis.

László Dávida, Vanda Pongrácz, Emir Awad Mohamed, Szilvia Szamosi, Gabriella Szücs, Andrea Váncsa, Orsolya Tímár, Zoltán Csiki, Edit Végh, Pál Soltész, Zoltán Szekanecz, György Kerekes
Author Information
  1. László Dávida: Intensive Care Unit, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
  2. Vanda Pongrácz: Intensive Care Unit, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
  3. Emir Awad Mohamed: Intensive Care Unit, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
  4. Szilvia Szamosi: Department of Rheumatology, Faculty of Medicine, University of Debrecen, Nagyerdei str 98, 4032, Debrecen, Hungary.
  5. Gabriella Szücs: Department of Rheumatology, Faculty of Medicine, University of Debrecen, Nagyerdei str 98, 4032, Debrecen, Hungary.
  6. Andrea Váncsa: Department of Rheumatology, Faculty of Medicine, University of Debrecen, Nagyerdei str 98, 4032, Debrecen, Hungary.
  7. Orsolya Tímár: Intensive Care Unit, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
  8. Zoltán Csiki: Division of Clinical Immunology, Department of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
  9. Edit Végh: Department of Rheumatology, Faculty of Medicine, University of Debrecen, Nagyerdei str 98, 4032, Debrecen, Hungary.
  10. Pál Soltész: Intensive Care Unit, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
  11. Zoltán Szekanecz: Department of Rheumatology, Faculty of Medicine, University of Debrecen, Nagyerdei str 98, 4032, Debrecen, Hungary. szekanecz.zoltan@med.unideb.hu.
  12. György Kerekes: Intensive Care Unit, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

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 (TH2 = 26.9 s vs. TH2 = 34.7 s, p = 0,032), and this effect prolonged until the end of treatment (TH2 = 40.5, p = 0.026; TH2 = 32.1, p = 0.013). After 8 weeks of treatment, significant improvement was found in AHa (AH = 1599 Perfusion Units [PU] vs. AH = 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.

Keywords

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Grants

  1. TAMOP-4.2.4.A/2-11/1-2012-0001/European Union
  2. GINOP-2.3.2-15-2016-00050/European Union
  3. GINOP-2.3.2-15-2016-00015/European Union

MeSH Term

Adalimumab
Adult
Aged
Antirheumatic Agents
Arthritis, Rheumatoid
Brachial Artery
Female
Humans
Longitudinal Studies
Male
Microcirculation
Middle Aged
Prospective Studies
Ultrasonography, Doppler
Vasodilation
Young Adult

Chemicals

Antirheumatic Agents
Adalimumab

Word Cloud

Created with Highcharts 10.0.0p = 0TH2treatmentRAstudyLDFadalimumabearlyfoundarthritishyperemiaendothelialFMDtimeTmaxvWF:AgdysfunctionrheumatoidmayfunctionpartdeterminedmicrocirculationPORHmeasuredlaserDopplerparametersTH1halfeffects8patients4significantR = 0R = - 0comparisonvseffectIncreasedcardiovascularCVmorbiditymortalityTumournecrosisfactorαTNF-αinhibitorsimprovevascularfirstpostoocclusivereactiverepresentingnonselectedpopulationn = 46flow-mediatedvasodilationbrachialarteryflowultrasoundAmongmaximumtotalhyperemicareaAHvonWillebrandantigenELISAsecondassessedmicrocirculatory0212 weekspositivecorrelations456002435004negativecorrelation009446003UpontherapytimesimprovedbaselineTH2 = 269 sTH2 = 347 s032prolongedendTH2 = 405026TH2 = 3210138 weeksimprovementAHaAH = 1599PerfusionUnits[PU]AH = 2724PU045testcarriedsensitiveoptionmeasureacceptablereproduciblemarkerspilotexertedfavorablediseaseactivityprospectivelongitudinalmonocentricimagingmicrocirculation:macrovascularpathophysiologyAdalimumabAtherosclerosisEndothelialFlow-mediatedvasodilatationLaserdopllerflowmetryMicrocirculationRheumatoid

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