Serum oxidized low-density lipoprotein decreases in response to statin therapy and relates independently to reductions in coronary plaque in patients with HIV

被引:51
作者
Nou, Eric [1 ]
Lu, Michael T. [2 ]
Looby, Sara E. [1 ]
Fitch, Kathleen V. [1 ]
Kim, Elli A. [1 ]
Lee, Hang [3 ]
Hoffmann, Udo [2 ]
Grinspoon, Steven K. [1 ]
Lo, Janet [1 ]
机构
[1] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA
[2] Massachusetts Gen Hosp, Cardiovasc Imaging Sect, Boston, MA 02114 USA
[3] Massachusetts Gen Hosp, Ctr Biostat, LON 207,55 Fruit St, Boston, MA 02114 USA
基金
美国国家卫生研究院;
关键词
atherosclerosis; cardiovascular; HIV; oxidized LDL; statin; ACUTE MYOCARDIAL-INFARCTION; SUBCLINICAL ATHEROSCLEROSIS; INFECTED PATIENTS; HEART-DISEASE; MONOCYTE ACTIVATION; ELEVATED LEVELS; PLASMA-LEVELS; RISK; INFLAMMATION; LDL;
D O I
10.1097/QAD.0000000000000946
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Objective:Circulating oxidized low-density lipoprotein (oxLDL) levels are elevated in HIV-infected patients and have been associated with atherosclerosis. Statins have been shown to reduce plaque on coronary computed tomography angiography (cCTA) in HIV-infected individuals. Thus, we investigated the effect of statins on serum oxLDL levels and the relationship between changes in oxLDL and coronary atherosclerosis on cCTA in patients with HIV.Design:We previously conducted a 12-month randomized, placebo-controlled trial with atorvastatin in 40 HIV-infected patients on stable antiretroviral therapy with subclinical coronary atherosclerosis and low-density lipoprotein (LDL)-cholesterol less than 130 mg/dl.Methods:In the current analysis, patients underwent cCTA and measurements of serum oxLDL, sCD14, sCD163, lipoprotein phospholipase-A(2), and fasting lipids at baseline and end of the study.Results:Nineteen patients were randomized to atorvastatin and 21 patients to placebo. Serum oxLDL decreased -22.7% (95% CI -28.7 to -16.7) in the atorvastatin group and increased 7.5% (95% CI -3.3 to 18.4) in the placebo group (P < 0.0001). Change in oxLDL significantly correlated with changes in noncalcified plaque volume, total plaque volume, positively remodeled plaque, and low attenuation plaque. The association between changes in oxLDL and noncalcified plaque volume was independent of the baseline 10-year Framingham risk, LDL, CD4(+) cell count, and viral load.Conclusion:Statins lower oxLDL levels in HIV-infected patients, and reductions in oxLDL are related to improvements in coronary atherosclerosis, independent of traditional cardiovascular risk factors. Reductions in oxLDL may be one mechanism through which statins exert beneficial effects on reducing atherosclerosis in HIV-infected individuals. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.
引用
收藏
页码:583 / 590
页数:8
相关论文
共 30 条
[1]   Plasma levels of oxidized-low-density lipoproteins are higher in patients with unstable angina and correlated with angiographic coronary complex plaques [J].
Anselmi, M ;
Garbin, U ;
Agostoni, P ;
Fusaro, M ;
Fratta Pasini, A ;
Nava, C ;
Keta, D ;
Turri, M ;
Zardini, P ;
Vassanelli, C ;
Lo Cascio, V ;
Cominacini, L .
ATHEROSCLEROSIS, 2006, 185 (01) :114-120
[2]   Differential associations between blood biomarkers of inflammation, oxidation, and lipid metabolism with varying forms of coronary atherosclerotic plaque as quantified by coronary CT angiography [J].
Bamberg, Fabian ;
Truong, Quynh A. ;
Koenig, Wolfgang ;
Schlett, Christopher L. ;
Nasir, Khurram ;
Butler, Javed ;
Kurtz, Emily ;
Nikolaou, Konstantin ;
Hoffmann, Udo ;
Januzzi, James L., Jr. .
INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING, 2012, 28 (01) :183-192
[3]   Concentration of circulating oxidized LDL in HIV-infected patients treated with antiretroviral agents: Relation to HIV-related lipodystrophy [J].
Duong, M ;
Petit, JM ;
Martha, B ;
Galland, F ;
Piroth, L ;
Walldner, A ;
Grappin, M ;
Buisson, M ;
Duvillard, L ;
Chavanet, P ;
Portier, H .
HIV CLINICAL TRIALS, 2006, 7 (02) :41-47
[4]   Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes [J].
Ehara, S ;
Ueda, M ;
Naruko, T ;
Haze, K ;
Itoh, A ;
Otsuka, M ;
Komatsu, R ;
Matsuo, T ;
Itabe, H ;
Takano, T ;
Tsukamoto, Y ;
Yoshiyama, M ;
Takeuchi, K ;
Yoshikawa, J ;
Becker, AE .
CIRCULATION, 2001, 103 (15) :1955-1960
[5]   HIV Infection and the Risk of Acute Myocardial Infarction [J].
Freiberg, Matthew S. ;
Chang, Chung-Chou H. ;
Kuller, Lewis H. ;
Skanderson, Melissa ;
Lowy, Elliott ;
Kraemer, Kevin L. ;
Butt, Adeel A. ;
Goetz, Matthew Bidwell ;
Leaf, David ;
Oursler, Kris Ann ;
Rimland, David ;
Barradas, Maria Rodriguez ;
Brown, Sheldon ;
Gibert, Cynthia ;
McGinnis, Kathy ;
Crothers, Kristina ;
Sico, Jason ;
Crane, Heidi ;
Warner, Alberta ;
Gottlieb, Stephen ;
Gottdiener, John ;
Tracy, Russell P. ;
Budoff, Matthew ;
Watson, Courtney ;
Armah, Kaku A. ;
Doebler, Donna ;
Bryant, Kendall ;
Justice, Amy C. .
JAMA INTERNAL MEDICINE, 2013, 173 (08) :614-622
[6]   Rosuvastatin Reduces Vascular Inflammation and T-cell and Monocyte Activation in HIV-Infected Subjects on Antiretroviral Therapy [J].
Funderburg, Nicholas T. ;
Jiang, Ying ;
Debanne, Sara M. ;
Labbato, Danielle ;
Juchnowski, Steven ;
Ferrari, Brian ;
Clagett, Brian ;
Robinson, Janet ;
Lederman, Michael M. ;
McComsey, Grace A. .
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 2015, 68 (04) :396-404
[7]   Shared monocyte subset phenotypes in HIV-1 infection and in uninfected subjects with acute coronary syndrome [J].
Funderburg, Nicholas T. ;
Zidar, David A. ;
Shive, Carey ;
Lioi, Anthony ;
Mudd, Joseph ;
Musselwhite, Laura W. ;
Simon, Daniel I. ;
Costa, Marco A. ;
Rodriguez, Benigno ;
Sieg, Scott F. ;
Lederman, Michael M. .
BLOOD, 2012, 120 (23) :4599-4608
[8]  
Hileman CO, 2014, 21 C RETR OPP INF CR
[9]   Measurement of plasma oxidized low-density lipoprotein and its clinical implications [J].
Itabe, Hiroyuki ;
Ueda, Makiko .
JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS, 2007, 14 (01) :1-11
[10]   Biomarkers of Microbial Translocation and Macrophage Activation: Association With Progression of Subclinical Atherosclerosis in HIV-1 Infection [J].
Kelesidis, Theodoros ;
Kendall, Michelle A. ;
Yang, Otto O. ;
Hodis, Howard N. ;
Currier, Judith S. .
JOURNAL OF INFECTIOUS DISEASES, 2012, 206 (10) :1558-1567