Association of Transcoronary Cytokine Gradients with Pericoronary Adipose Tissue Attenuation: A Transcoronary and Transcardiac sampling study

Background: Pericoronary adipose tissue (PCAT) attenuation on coronary computed tomography angiography (CTCA) has emerged as a novel non-invasive biomarker of coronary inflammation and cardiovascular risk. The degree to which PCAT reflects local or systemic inflammation remains uncertain. We hypothesized that the presence, location and extent of PCAT would be associated with transcoronary or transcardiac cytokine gradient. Methods: This prospective cohort study involved 31 adults with stable coronary artery disease who underwent clinically indicated CTCA within 90 days of invasive coronary angiography. Patients with acute coronary syndromes or unstable angina were excluded. Blood samples were obtained from peripheral vein, coronary sinus, aortic root, and right coronary artery at time of cardiac catheterization. Plasma interleukin-6 (IL-6) and interleukin-1{beta} (IL-1{beta}) concentrations from each site were used to calculate transcardiac and transcoronary cytokine gradients. PCAT attenuation was measured using semi-automatic software by readers blinded to clinical and biochemical endpoints. Results: Participants were predominantly male (76%), aged 66.6 {+/-} 9.4 years, with a high prevalence of hypercholesterolemia (76%), hypertension (73%), and diabetes (36%). Mean PCAT attenuation was -74.8 HU (RCA), -70.3 HU (LCx), and -73.6 HU (LAD). Regression analyses showed no significant associations between PCAT attenuation and IL-6 gradients across any coronary territory (all p >0.40; R2 {approx} 0), including in plaque-free subgroup analyses. IL-1{beta} was below the assay detection limit in 81% of participants; analyses using non-parametric testing and logistic no association with PCAT attenuation. RCA (OR 0.96, 95% CI 0.88-1.06, p=0.46), LCx (OR 1.00, 95% CI 0.91-1.09, p=0.94), LAD (OR 0.99, 95% CI 0.90-1.08, p=0.81). Conclusion: In a cohort with predominantly stable coronary disease, PCAT attenuation was not associated with intracardiac or intracoronary IL-6 or IL-1{beta} gradients, including in plaque-free vessels. These findings suggest that PCAT attenuation may not reflect active cytokine-mediated coronary inflammation in stable disease.