Abstract

BackgroundMethotrexate (MTX) is well known to affect folic acid metabolism, so MTX treatment can result in alterations of mean corpuscular volume (MCV), which may impact on red cell distribution width (RDW), as MCV levels feed into RDW calculation. We thus questioned whether RDW levels and subsequently its diagnostic utility in RA subjects, as reported before, are influenced by ongoing MTX therapy.We assessed the impact of disease modifying drug (DMARD) treatment, especially MTX, on RDW and evaluated their influence on the predictive value of RDW for cardiovascular (CV) events in patients with rheumatoid arthritis (RA). As far as we know, this is the first study evaluating the influence of MTX on RDW.MethodsMedical treatment, disease activity, laboratory parameters and history of CV events were retrospectively analysed in 385 RA patients at disease onset and at last follow up at our clinic. Additionally, in patients with CV event, data were recorded at last follow up prior the CV event.ResultsDisease parameters and laboratory findings associated with a serious vascular event were older age (p < 0,001), longer disease duration (p = 0,002) and a higher RDW at diagnosis (p = 0,025). No differences in RDW levels became evident with any other treatment regimen beside MTX. MTX treated patients had significantly higher RDW compared to subjects without this drug (p < 0,001). In RA patients without MTX treatment, we found RDW level significantly different between those with versus without a CV event, whereas this difference disappeared in subjects receiving MTX.ConclusionMTX impacts on RDW and might therefor reduce its prognostic value for CV events in patients taking MTX, whereas an increased RDW at diagnosis remains an early risk predictor for myocardial infarction and stroke in RA patients.

Highlights

  • Methotrexate (MTX) is well known to affect folic acid metabolism, so MTX treatment can result in alterations of mean corpuscular volume (MCV), which may impact on red cell distribution width (RDW), as MCV levels feed into RDW calculation

  • The mean duration of rheumatoid arthritis (RA) was 14,5 years (SD 11,9), 77,2% of patients were positive for anti-citrullinated-peptide-antibodies (ACPA) and 73,5% of patients had a positive rheumatoid factor (RF) test, both parameters linked to disease severity in RA [24]

  • We studied for associations between disease activity, measured by Disease activity score 28 (DAS-28)-C-reactive protein (CRP), haematological parameters (RDW and MCV at last visit or last visit before a CV event) and csDMARDs therapy in patients with or without a CV event

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Summary

Introduction

Methotrexate (MTX) is well known to affect folic acid metabolism, so MTX treatment can result in alterations of mean corpuscular volume (MCV), which may impact on red cell distribution width (RDW), as MCV levels feed into RDW calculation. We questioned whether RDW levels and subsequently its diagnostic utility in RA subjects, as reported before, are influenced by ongoing MTX therapy. We assessed the impact of disease modifying drug (DMARD) treatment, especially MTX, on RDW and evaluated their influence on the predictive value of RDW for cardiovascular (CV) events in patients with rheumatoid arthritis (RA). A retrospective analysis of > 20.000 patients with RA indicated that higher RDW, as well as increased levels of markers of inflammation, like C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR), were associated with an increased risk of a subsequent CV event in RA-patients [12]. The described positive association between IFN-alpha, a cytokine contributing to endothelial damage, and RDW would be in agreement with this concept [14]

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