Identifying Vulnerable Plaque in Rheumatoid Arthritis Using Novel Microbubble Contrast-Enhanced Carotid Ultrasonography and Serum Biomarkers

Objective: Rheumatoid arthritis (RA) is associated with increased risk of cardiovascular disease. Adventitial vasa vasorum density (aVVD), the vessel density of the vasa vasorum, is a surrogate measure for atherosclerotic plaque vulnerability. The purpose of this study was to compare the adventitial vasa vasorum density (aVVD) in RA and non-RA control participants using novel carotid artery contrast-enhanced ultrasound (CEUS). In addition, we investigate associations of aVVD with traditional cardiovascular (CV) risk factors, vascular and inflammatory biomarkers, and RA disease activity. Methods: The study was a cross-sectional analysis of patients with RA and control participants without RA or other autoimmune disease. CV disease risk, biomarkers, and CEUS images were collected on all patients. Results: aVVD was quantified in 86 patients with RA and 95 non-RA control participants. Nitrite, CD40L, E-selectin, matrix metalloproteinase 9, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, myeloperoxidase (MPO), high-sensitivity C-reactive protein (hsCRP), and erythrocyte sedimentation rate were measured. Median aVVD was higher in patients with RA (0.59 [0.47–0.69] vs 0.64 [0.54–0.62]; P = .02). In patients with RA, MPO was lower (253.5 [153.2–480] vs 470.8 [274.2–830.1] ng/mL; P = .0002) and ESR was higher (15.5 [11–25] vs 13 [9–20] mm/h; P = .02). aVVD was correlated with MPO (r = −0.33, P = .001) and hsCRP (r = 0.25, P = .02) in control participants only, associations that remained significant after adjusting for number of CV risk factors and age. No significant correlations were found between aVVD and RA disease activity measures. Conclusions: Using a novel application of CEUS, we found that aVVD, an early measure of plaque vulnerability, was significantly higher in RA than control subjects, even after adjusting for CV risk factors. Differences in correlation of aVVD with vascular biomarkers and CV risk factors suggest RA-related differences in atherosclerotic progression.