Red cell distribution width is associated with endothelial progenitor cell depletion and vascular-related mediators in rheumatoid arthritis

- RDW was independently associated to EPC depletion in RA patients.
- RDW was associated to inflammatory and vascular-related soluble mediators in RA patients.
- Associations of RDW were dependent on disease course in RA.
- These findings were independent of traditional CV risk factors and treatments.

ObjectivesThe role of Red Cell Distribution Width (RDW) as a predictor of cardiovascular (CV) events has been proposed in a variety of conditions, including Rheumatoid Arthritis (RA). However, the mechanisms underlying this effect are still unknown. Since inflammation and Endothelial Progenitor Cells (EPCs) imbalance have been reported in RA patients to be related to CV disease, we wondered whether RDW could be linked to endothelial repair failure in RA.MethodsEPCs (CD34+VEGFR2+CD133+) were quantified by flow cytometry in peripheral blood samples from 194 RA patients. IFNα, TNFα, IFNγ, IL-8, VEGF, GM-CSF, MCP-1, ICAM-1, EGF, Leptin and Resistin serum levels were quantified by immunoassays. Clinical and immunological parameters as well as history of traditional CV risk factors and CV events were registered from medical records. RDW was measured in complete blood cell count analyses.ResultsRDW was negatively related to EPC counts in patients with established disease (>1 year, n = 125) (r = −0.306, p < 0.001). Moreover, RDW was independently associated to an EPC depletion in the whole group (β [95% CI]: −3.537 [−6.162, −0.911], p = 0.009) after adjusting for clinical parameters, disease duration, treatments and traditional CV risk factors. Additionally, RDW was positively correlated with IFNα serum levels, a cytokine related to endothelial damage, and with IL-8, VEGF and neutrophil to lymphocyte ratio, thus supporting the association with inflammation and vascular remodelling.ConclusionsRDW was associated to EPC depletion and increased levels of different mediators linked to endothelial damage and vascular repair failure, thereby shedding new light on the nature of RDW as CV-predictor.