title: Circulating cytokines in relation to the extent and composition of coronary atherosclerosis: results from the ATHEROREMO-IVUS study.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Clinical Epidemiology Unit, Department of Cardiology, Erasmus MC, Thoraxcenter, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: battes@erasmusmc.nl.
authors.forename: Linda C
authors.initials: LC
authors.lastname: Battes
authors.affiliation: Clinical Epidemiology Unit, Department of Cardiology, Erasmus MC, Thoraxcenter, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: j.cheng@erasmusmc.nl.
authors.forename: Jin M
authors.initials: JM
authors.lastname: Cheng
authors.affiliation: Clinical Epidemiology Unit, Department of Cardiology, Erasmus MC, Thoraxcenter, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: r.oemrawsingh@erasmusmc.nl.
authors.forename: Rohit M
authors.initials: RM
authors.lastname: Oemrawsingh
authors.affiliation: Clinical Epidemiology Unit, Department of Cardiology, Erasmus MC, Thoraxcenter, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.
authors.forename: Eric
authors.initials: E
authors.lastname: Boersma
authors.affiliation: Clinical Epidemiology Unit, Department of Cardiology, Erasmus MC, Thoraxcenter, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: h.garciagarcia@erasmusmc.nl.
authors.forename: Hector M
authors.initials: HM
authors.lastname: Garcia-Garcia
authors.affiliation: Clinical Epidemiology Unit, Department of Cardiology, Erasmus MC, Thoraxcenter, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: s.p.m.deboer@erasmusmc.nl.
authors.forename: Sanneke P M
authors.initials: SP
authors.lastname: de Boer
authors.affiliation: Clinical Epidemiology Unit, Department of Cardiology, Erasmus MC, Thoraxcenter, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: n.buljubasic@erasmusmc.nl.
authors.forename: Nermina
authors.initials: N
authors.lastname: Buljubasic
authors.affiliation: Clinical Epidemiology Unit, Department of Cardiology, Erasmus MC, Thoraxcenter, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: n.vanmieghem@erasmusmc.nl.
authors.forename: Nicolas A van
authors.initials: NA
authors.lastname: Mieghem
authors.affiliation: Clinical Epidemiology Unit, Department of Cardiology, Erasmus MC, Thoraxcenter, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: e.regar@erasmusmc.nl.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Regar
authors.affiliation: Clinical Epidemiology Unit, Department of Cardiology, Erasmus MC, Thoraxcenter, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: r.vangeuns@erasmusmc.nl.
authors.forename: Robert-Jan van
authors.initials: RJ
authors.lastname: Geuns
authors.affiliation: Clinical Epidemiology Unit, Department of Cardiology, Erasmus MC, Thoraxcenter, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: p.w.j.c.serruys@erasmusmc.nl.
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Serruys
authors.affiliation: Clinical Epidemiology Unit, Department of Cardiology, Erasmus MC, Thoraxcenter, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: k.m.akkerhuis@erasmusmc.nl.
authors.forename: K Martijn
authors.initials: KM
authors.lastname: Akkerhuis
authors.affiliation: Clinical Epidemiology Unit, Department of Cardiology, Erasmus MC, Thoraxcenter, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. Electronic address: i.kardys@erasmusmc.nl.
authors.forename: Isabella
authors.initials: I
authors.lastname: Kardys
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000000981:diagnostic imaging / Q000473:pathology; D000368:Aged; D000787:Angina Pectoris / Q000097:blood / Q000000981:diagnostic imaging / Q000473:pathology; D015415:Biomarkers; D015897:Comorbidity; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood* / Q000000981:diagnostic imaging / Q000473:pathology; D016207:Cytokines / Q000097:blood*; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000000981:diagnostic imaging / Q000473:pathology; D012307:Risk Factors; D018084:Ultrasonography, Interventional
chemical_list: D015415:Biomarkers; D016207:Cytokines
keywords: Atherosclerosis; Biomarker; Cytokine; Intravascular ultrasound