Elevated CETP activity during acute phase of myocardial infarction is independently associated with endothelial dysfunction and adverse clinical outcome Luiz Sergio F. Carvalho a , Vitor W.M. Virginio a, b , Natalia B. Panzoldo a, b , Valeria N. Figueiredo a , Simone N. Santos a , Rodrigo G.P. Modolo a , Joalbo M. Andrade c , Jose C. Quinaglia e Silva d , Wilson Nadruz-Junior a , Eliana C. de Faria b , Andrei C. Sposito a, * , onbehalf of the Brasilia Heart Study Group a Cardiology Division, State University of Campinas School of Medicine (Unicamp), Campinas, SP, Brazil b Lipids Laboratory, State University of Campinas School of Medicine (Unicamp), Campinas, SP, Brazil c University of Brasília, Brasilia, DF, Brazil d Escola Superior de Ciencias da Saúde (ESCS), Brasilia, DF, Brazil article info Article history: Received 6 September 2014 Received in revised form 13 October 2014 Accepted 28 October 2014 Available online 4 November 2014 Keywords: CETP Myocardial infarction Endothelial dysfunction Inflammation Oxidized HDL abstract Objective: Recent data suggests that cholesteryl ester transfer protein (CETP) activity may interact with acute stress conditions via inflammatory-oxidative response and thrombogenesis. We investigated this assumption in patients with ST-elevation myocardial infarction (STEMI). Methods: Consecutive patients with STEMI (n ¼ 116) were enrolled <24-h of symptoms onset and were followed for 180 days. Plasma levels of C-reactive protein (CRP), interleukin-2 (IL-2), tumor necrosis factor (TNFa), 8-isoprostane, nitric oxide (NO x ) and CETP activity were measured at enrollment (D1) and at fifth day (D5). Flow-mediated dilation (FMD) was assessed by ultrasound and coronary thrombus burden (CTB) was evaluated by angiography. Results: Neither baseline nor the change of CETP activity from D1 to D5 was associated with CRP, IL-2, TNFa, 8-isoprostane levels or CTB. The rise in NO x from D1 to D5 was inferior [3.5(1; 10) vs. 5.5(1; 12); p < 0.001] and FMD was lower [5.9(5.5) vs. 9.6(6.6); p ¼ 0.047] in patients with baseline CETP activity above the median value than in their counterparts. Oxidized HDL was measured by thio- barbituric acid reactive substances (TBARS) in isolated HDL particles and increased from D1 to D5, and remaining elevated at D30. The change in TBARS content in HDL was associated with CETP activity (r ¼ 0.72; p ¼ 0.014) and FMD (r ¼0.61; p ¼ 0.046). High CETP activity at admission was associated with the incidence of sudden death and recurrent MI at 30 days (OR 12.8; 95% CI 1.25e132; p ¼ 0.032) and 180 days (OR 3.3; 95% CI 1.03e10.7; p ¼ 0.044). Conclusions: An enhanced CETP activity during acute phase of STEMI is independently associated with endothelial dysfunction and adverse clinical outcome. © 2014 Elsevier Ireland Ltd. All rights reserved. 1. Introduction The cholesteryl ester transfer protein (CETP) has as its most explored role on cardiovascular disease the mediation of choles- teryl esters exchange for triglycerides between high-density lipo- proteins (HDL) and lipoproteins containing apolipoprotein (apo) B. Recently, novel direct involvement of CETP in acute phase inflammatory response [1] and thrombogenesis [2] have been revealed as other potential mechanisms to influence clinical outcomes. In severe sepsis, in-hospital mortality was reported to be inversely related to CETP activity [3]. In transgenic animal models of sepsis, CETP mediates the transfer of circulating endotoxins to HDL, increasing their hepatic uptake and attenuating the systemic inflammatory response [1]. Hypothetically, such an effect may also be beneficial during acute phase myocardial infarction (MI), when oxidative-inflammatory response is a strong determinant of short and long-term mortality [4]. So far, however, data is unavailable to verify this assumption. In parallel, recent data also reveal a positive association between plasma CETP activity and activation of * Corresponding author. Cardiology Division, Faculty of Medical Sciences, State University of Campinas (Unicamp), 13084-971 Campinas, Sao Paulo, Brazil. E-mail address: andreisposito@gmail.com (A.C. Sposito). Contents lists available at ScienceDirect Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis http://dx.doi.org/10.1016/j.atherosclerosis.2014.10.104 0021-9150/© 2014 Elsevier Ireland Ltd. All rights reserved. Atherosclerosis 237 (2014) 777e783