1955: Regional variations in the relationship between pericoronary fat enhancement and atherosclerosis may reflect differences in local vascular inflammation in rheumatoid arthritis

Background/Purpose: The composition of fat around the coronary arteries is evaluated as pericoronary adipose tissue attenuation (PCATa) on coronary CT-angiogram (CCTA). In general patients PCATa was linked to plaque burden and cardiovascular risk independently of epicardial adipose tissue volume (EATv) and is considered to reflect arterial inflammation. In the presence of plaque and an inflamed vessel wall, higher EATv offset inflammation in PCAT and inversely associated with PCATa. Rheumatoid arthritis (RA) therapies attenuated EATv, arterial inflammation, plaque progression and promoted plaque stabilization via fibrosis and calcification. We here explore the relationships between artery-specific PCATa and atherosclerosis burden in the respective arteries, the influence of methotrexate, prednisone and statin use on those relationships and the link between artery-specific PCATa and inflammation in RA.

Methods: PCATa around proximal left anterior descending (LAD), left circumflex (LCx) and right coronary artery (RCA), total EATv, atherosclerosis burden and composition (noncalcified, mixed and calcified) were evaluated with CCTA in 150 RA patients without known coronary artery disease. Serum cytokines were measured with microparticle immunoassay. Negative binomial regression explored associations of artery-specific PCATa and its interactions with methotrexate, prednisone and statin use on plaque numbers (total and subtypes) and stenotic severity in underlying coronary segments. Robust linear regression assessed associations of cytokines with artery-specific PCATa.

Results: Artery-specific PCATa was linked to artery-specific plaque burden and composition exclusively for LCx (all p< 0.05, Figure 1A). Each standard deviation increase in PCATa only around LCx associated with 85% greater likelihood of plaque presence in directly underlying segments (odds ratio-OR 1.85, 95% confidence interval 1.12-3.06) and greater stenotic severity (Figure 1B,C). Plaque presence only in LCx, but not other arteries, influenced the relationship between PCATa and EATv: PCATa around LCx inversely associated with EATv only in the presence of plaque (p for interaction< 0.05, Figure 2A). PCATa around LCx associated with interleukin-17F (figure 2B), and plaque presence exclusively in LCx influenced the relationship between PCATa and IL-17A (p for interaction < 0.01). Likewise, in the presence of mixed plaque exclusively in LCx, PCATa around LCx associated with serum vascular endothelial growth factor (VEGF, p for interaction=0.002). Lastly, PCATa associated with more noncalcified plaques in the absence of methotrexate, prednisone, or statin use (all p-for-interactions< 0.05) exclusively in LCx.

Conclusion: The association of increased PCATa with atherosclerosis burden and composition specifically around LCx may coincide with regional inflammation-dependent compositional changes in PCAT including IL-17A,F-induced adipocyte remodeling and VEGF-induced neovascularization and edema. In contrast, post-inflammatory fibrosis or adaptive remodeling may account for increased PCATa and the lack of association with plaque in LAD and RCA.