ABC | Volume 111, Nº3, September 2018

Original Article Adiponectin in Relation to Coronary Plaque Characteristics on Radiofrequency Intravascular Ultrasound and Cardiovascular Outcome Bárbara Campos Abreu Marino, 1,2 Nermina Buljubasic, 1 Martijn Akkerhuis, 1 Jin M. Cheng, 1 Hector M. Garcia-Garcia, 3 Evelyn Regar, 1,4 Robert-Jan van Geuns, 1 Patrick W. Serruys, 5 Eric Boersma, 1 Isabella Kardys 1 Department of Cardiology, Erasmus MC, 1 Rotterdam - the Netherlands Universidade Federal de Minas Gerais (UFMG), 2 Belo Horizonte, MG - Brasil Washington Hospital Center, 3 Washington DC - USA University Hospital of Zurich, 4 Zurich - Switzerland Imperial College, 5 London - United Kingdom Mailing Address: Isabella Kardys • P.O. Box 2040. 3000CA, Rotterdam E-mail: i.kardys@erasmusmc.nl Manuscript received November 13, 2017, revised manuscript April 11, 2018, accepted April 11, 2018 DOI: 10.5935/abc.20180172 Abstract Background: Prospective data on the associations of adiponectin with in-vivo measurements of degree, phenotype and vulnerability of coronary atherosclerosis are currently lacking. Objective: To investigate the association of plasma adiponectin with virtual histology intravascular ultrasound (VH‑IVUS)- derived measures of atherosclerosis and with major adverse cardiac events (MACE) in patients with established coronary artery disease. Methods: In 2008-2011, VH-IVUS of a non-culprit non-stenotic coronary segment was performed in 581 patients undergoing coronary angiography for acute coronary syndrome (ACS, n = 318) or stable angina pectoris (SAP, n = 263) from the atherosclerosis-intravascular ultrasound (ATHEROREMO-IVUS) study. Blood was sampled prior to coronary angiography. Coronary plaque burden, tissue composition, high-risk lesions, including VH-IVUS-derived thin-cap fibroatheroma (TCFA), were assessed. All-cause mortality, ACS, unplanned coronary revascularization were registered during a 1-year-follow-up. All statistical tests were two-tailed and p-values < 0.05 were considered statistically significant. Results: In the full cohort, adiponectin levels were not associated with plaque burden, nor with the various VH-tissue types. In SAP patients, adiponectin levels (median[IQR]: 2.9(1.9-3.9) μg/mL) were positively associated with VH-IVUS derived TCFA lesions, (OR[95%CI]: 1.78[1.06-3.00], p = 0.030), and inversely associated with lesions with minimal luminal area (MLA) ≤ 4.0 mm 2 (OR[95%CI]: 0.55[0.32-0.92], p = 0.025). In ACS patients, adiponectin levels (median[IQR]: 2.9 [1.8‑4.1] μg/mL)were not associatedwith plaque burden, nor with tissue components. Positive association of adiponectin with death was present in the full cohort (HR[95%CI]: 2.52[1.02–6.23], p = 0.045) and (borderline) in SAP patients (HR[95%CI]: 8.48[0.92–78.0], p = 0.058). In ACS patients, this association lost statistical significance after multivariable adjustment (HR[95%CI]: 1.87[0.67-5.19], p = 0.23). Conclusion: In the full cohort, adiponectin levels were associated with death but not with VH-IVUS atherosclerosis measures. In SAP patients, adiponectin levels were associated with VH-IVUS-derived TCFA lesions. Altogether, substantial role for adiponectin in plaque vulnerability remains unconfirmed. (Arq Bras Cardiol. 2018; 111(3):345-353) Keywords: Adiponectin; Atherosclerosis; Plaque, Atherosclerotic; Ultrasonography, Interventional; Coronary Artery Disease / complications. Introduction Coronary plaque rupture has been described as the main mechanism through which mildly stenotic coronary atherosclerosis can lead to acute coronary thrombosis and myocardial infarction. 1 High-risk plaques that are vulnerable to such rupture demonstrate distinct morphological characteristics. 2 They can be differentiated from lesions responsible for stable coronary artery disease (CAD) by their large necrotic cores, thin inflamed fibrous caps, and positive remodeling. 2 Because plaque vulnerability is associated with inflammation, neovascularization, and necrotic core formation, circulating mediators of these processes may aid in detection of high-risk patients and therefore warrant investigation. 3 One important inflammatory mediator of CAD is adiponectin. Adiponectin is a protein mainly produced in white adipose tissue, involved in several antioxidant, anti- inflammatory, and anti-atherosclerotic processes. 4-6 Several studies have demonstrated associations of adiponectin with clinical adverse coronary events. 7-10 Yet, prospective data on the associations of adiponectin with in‑vivo measurements of degree, phenotype and vulnerability of coronary atherosclerosis are currently lacking. To further elucidate the pathophysiology of adiponectin in patients 345