Circulating cytokines in relation to the extent and composition of coronary atherosclerosis: Results from the ATHEROREMO-IVUS study

Objective: We investigated whether concentrations of TNF-α, TNF-β, TNF-receptor 2, interferon-γ, IL-6, IL-8, IL-10 and IL-18 are associated with extent and composition of coronary atherosclerosis determined by grayscale and virtual histology (VH)- intravascular ultrasound (IVUS). Methods: Between 2008 and 2011, IVUS(-VH) imaging of a non-culprit coronary artery was performed in 581 patients (stable angina pectoris (SAP), n=261; acute coronary syndrome (ACS), n=309) undergoing coronary angiography from the ATHEROREMO-IVUS study. Plaque burden, presence of VH-IVUS-derived thin-cap fibroatheroma (TCFA) lesions, and presence of VH-TCFA lesions with plaque burden ®70% were assessed. Blood samples for cytokine measurement were drawn from the arterial sheath prior to the angiography procedure. We applied linear and logistic regression. Results: TNF-α levels were positively associated with plaque burden (beta (β) [95%CI]: 4.45 [0.99-7.91], for highest vs lowest TNF-α tertile) and presence of VH-TCFA lesions (odds ratio (OR) [95%CI] 2.30 (1.17-4.52), highest vs lowest TNF-α tertile) in SAP patients. Overall, an inverse association was found between IL-10 concentration and plaque burden (β [95%CI]:-1.52 [-2.49 to -0.55], per Ln (pg/mL) IL-10) as well as IL-10 and VH-TCFA lesions with plaque burden ®70% (OR: 0.31 [0.12-0.80],highest vs lowest IL-10 tertile). These effects did not reach statistical significance in the separate SAP and ACS groups. Conclusion: Higher circulating TNF-α was associated with higher plaque burden and VH-TCFA lesions in SAP patients. Lower circulating IL-10 was associated with higher plaque burden and large VH-TCFA lesions. These in-vivo findings suggest a role for these cytokines in extent and vulnerability of atherosclerosis.