Background/Purpose:   A key unmet need in the monitoring of disease activity in large vessel vasculitides (LVV), i.e., giant cell arteritis (GCA) and Takayasu arteritis (TAK), is the ability to differentiate active vasculitic disease activity from atherosclerotic damage through the use of noninvasive imaging modalities. In LVV, the inflammatory process begins at the vasa vasorum in the adventitia, with vasa vasoritis and inflammatory cell recruitment. Thickened adventitia and medial fibrosis are key features that differentiate vasculitis from atherosclerosis. A novel imaging modality that can noninvasively detect increased neovascularization and thickening in large vessels’ adventitia is microbubble contrast-enhanced carotid ultrasonography (CU). In animal and human studies using CU, higher densities of vasa vasorum correlated with plaque vulnerability and atherosclerosis progression. Our objective was to establish feasibility of measuring adventitial vasa vasorum density (aVVD) in LVV patients; to compare aVVD in clinically active vs. inactive LVV patients; and to examine various serum vascular and inflammatory biomarkers in these patients.

Methods:   We performed a preliminary analysis of an ongoing cross-sectional study of 7 LVV patients (2 active, 5 inactive) to illustrate feasibility of the novel CU technique. All subjects met ACR criteria for GCA or TAK. All subjects underwent CU with measurement of carotid intima-media thickness (cIMT, using maximum of both sides) and mean common carotid artery (CCA) adventitial to lumen videointensity ratio (using maximum of both sides) to quantify aVVD. Data on demographics and disease characteristics were collected on all subjects. Serum biomarkers of CD40L, matrix metalloproteinase-9, myeloperoxidase, E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 were measured in all subjects by enzyme-linked immunosorbent assay (ELISA). The inflammatory markers high sensitivity C-reactive protein and erythrocyte sedimentation rate were also measured in all patients.

Results:   Table 1 shows results of type of LVV, disease activity status, demographic data, cIMT, and aVVD of all 7 subjects. The mean cIMT of the two active LVV subjects was 1.23 mm, and the mean cIMT of four inactive subjects was 0.91 mm. The maximal aVVD of the CCA’s far wall for the two active LVV subjects was 0.58, versus 0.50 for the five inactive LVV subjects. Wide variation in serum biomarker levels were seen in the inactive subgroup, and statistical testing will be performed when the study of n=20 participants is completed to compare if the levels are higher in the active vs. inactive subgroups.

Conclusion:   Measurement of aVVD in LVV patients is feasible utilizing the novel CU technique. In this pilot study, the aVVD was slightly higher in active vs. inactive subjects. Our study is ongoing, with plans for targeted enrollment of larger numbers and comparison with control (non-LVV) subjects.   Table 1.

LVV = large vessel vasculitis; GCA = giant cell arteritis; TAK = Takayasu arteritis; BMI = body mass index; cIMT = carotid intima media thickness; aVVD = ratio of adventitial to lumen vasa vasorum density *Unobtainable bilaterally due to Goretex graft in right CCA and occlusion of left CCA