Angiopoietin-2, vascular endothelial growth factor family, and heparin binding endothelial growth factor are associated with subclinical atherosclerosis in rheumatoid arthritis

Introduction: Patients with RA are at a higher risk of developing CV diseases than the general population. The precise mechanisms are still unknown. We evaluated the associations between 8 plasma growth factors (GFs) (angiopoietin-2, EGF, HB-EGF, PLGF, TGF-α, VEGFa, VEGFc, and VEGFd) and subclinical arteriosclerosis in RA patients. Materials and methods: A total of 199 patients with RA treated at the Hospital Universitari Sant Joan de Reus (Spain) between 2011 and 2015 were included in this cross-sectional study. Carotid intima media thickness (cIMT), carotid plaque presence (cPP) and pulse wave velocity (PWV) were measured. GFs were measured with Bio-Plex Pro Human Cancer Biomarker Panel 2 (Bio-Rad). Multivariate models and partial least square discriminant analysis (PLS-DA) were used for analysis (RStudio, version 4.0.1). Results: Multivariate models showed that angiopoietin-2 was associated with cPP and PWV in the overall cohort (OR = 1.53 and β = 0.20, respectively). VEGFc (β = 0.29), VEGFa (β = 0.26) and HB-EGF (β = 0.22) were also associated with PWV. VEGFa (OR = 2.36), VEGFd (OR = 2.29), EGF (OR = 2.62), PLGF (OR = 2.54), and HB-EGF (OR = 2.24) were associated with cPP in men. According to PLS-DA, GFs were able to distinguish between patients with and without cPP in the overall cohort, male cohort, and female cohort. In women, angiopoietin-2 was associated with PWV (β = 0.18). Conclusions: The selected GFs were closely related to atherosclerosis in patients with RA and are potential predictors of CV disease in patients with RA.