title: Relationship of oxidized phospholipids on apolipoprotein B-100 to cardiovascular outcomes in patients treated with intensive versus moderate atorvastatin therapy: the TNT trial.
abstract: BACKGROUND
  Oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB) is a biomarker of increased risk for major adverse cardiovascular events (MACE) in community cohorts, but its role in patients with stable coronary heart disease (CHD) is unknown.
  
  
  OBJECTIVE
  This study sought to examine the relationship between these oxidative biomarkers and cardiovascular outcomes in patients with established CHD.
  
  
  METHODS
  In a random sample from the TNT (Treating to New Targets) trial, OxPL-apoB levels were measured in 1,503 patients at randomization (after an 8-week run-in period taking atorvastatin 10 mg) and 1 year after being randomized to atorvastatin 10 or 80 mg. We examined the association between baseline levels of OxPL-apoB and MACE, defined as death from CHD, nonfatal myocardial infarction, resuscitation after cardiac arrest, and fatal/nonfatal stroke, as well as the effect of statin therapy on OxPL-apoB levels and MACE.
  
  
  RESULTS
  Patients with events (n = 156) had higher randomization levels of OxPL-apoB than those without events (p = 0.025). For the overall cohort, randomization levels of OxPL-apoB predicted subsequent MACE (hazard ratio [HR]: 1.21; 95% confidence interval: 1.04 to 1.41; p = 0.018) per doubling and tertile 3 versus tertile 1 (hazard ratio: 1.69; 95% confidence interval [CI]: 1.14 to 2.49; p = 0.01) after multivariate adjustment for age, sex, body mass index, among others, and treatment assignment. In the atorvastatin 10-mg group, tertile 3 was associated with a higher risk of MACE compared to the first tertile (HR: 2.08; 95% CI: 1.20 to 3.61; p = 0.01) but this was not significant in the atorvastatin 80-mg group (HR: 1.40; 95% CI: 0.80 to 2.46; p = 0.24).
  
  
  CONCLUSIONS
  Elevated OxPL-apoB levels predict secondary MACE in patients with stable CHD, a risk that is mitigated by atorvastatin 80 mg. (A Study to Determine the Degree of Additional Reduction in CV Risk in Lowering LDL Below Minimum Target Levels [TNT]; NCT00327691).
authors.affiliation: Division of Cardiovascular Diseases, University of California San Diego, La Jolla, California; Division of Cardiology, Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, South Korea.
authors.forename: Young Sup
authors.initials: YS
authors.lastname: Byun
authors.affiliation: Division of Cardiovascular Diseases, University of California San Diego, La Jolla, California; Division of Cardiology, Kang-Dong Sacred Heart Hospital, Hallym University Medical Center, Seoul, South Korea.
authors.forename: Jun-Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Quebec City, Quebec, Canada.
authors.forename: Benoit J
authors.initials: BJ
authors.lastname: Arsenault
authors.affiliation: Division of Cardiovascular Diseases, University of California San Diego, La Jolla, California.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Yang
authors.affiliation: Pfizer, Inc., New York, New York.
authors.forename: Weihang
authors.initials: W
authors.lastname: Bao
authors.affiliation: Pfizer, Inc., New York, New York.
authors.forename: David
authors.initials: D
authors.lastname: DeMicco
authors.affiliation: Pfizer, Inc., New York, New York.
authors.forename: Rachel
authors.initials: R
authors.lastname: Laskey
authors.affiliation: Division of Endocrinology/Metabolism, University of California San Diego, La Jolla, California.
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Witztum
authors.affiliation: Division of Cardiovascular Diseases, University of California San Diego, La Jolla, California. Electronic address: stsimikas@ucsd.edu.
authors.forename: Sotirios
authors.initials: S
authors.lastname: Tsimikas
mesh_terms: D000368:Aged; D053299:Apolipoprotein B-100 / Q000097:blood*; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000209:etiology*; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000097:blood*; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use*; D012307:Risk Factors
chemical_list: D053299:Apolipoprotein B-100; D015415:Biomarkers; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010743:Phospholipids; D011758:Pyrroles; D000069059:Atorvastatin
keywords: atherosclerosis; biomarker; coronary heart disease; inflammatory; oxidation-specific epitope
references.citation: Arterioscler Thromb Vasc Biol. 2004 Mar;24(3):498-503
references.pmid: 14739118
references.citation: J Am Coll Cardiol. 2003 Feb 5;41(3):360-70
references.pmid: 12575961
references.citation: Circulation. 2004 Sep 14;110(11):1406-12
references.pmid: 15353498
references.citation: N Engl J Med. 2005 Apr 7;352(14):1425-35
references.pmid: 15755765
references.citation: J Am Coll Cardiol. 2006 May 2;47(9):1803-10
references.pmid: 16682304
references.citation: Arterioscler Thromb Vasc Biol. 2007 Jan;27(1):175-81
references.pmid: 17082490
references.citation: J Am Coll Cardiol. 2008 Apr 29;51(17):1653-62
references.pmid: 18436117
references.citation: Circulation. 2009 Apr 7;119(13):1711-9
references.pmid: 19307470
references.citation: J Lipid Res. 2008 Oct;49(10):2230-9
references.pmid: 18594118
references.citation: J Am Coll Cardiol. 2008 Jun 10;51(23):2228-9
references.pmid: 18534268
references.citation: J Am Coll Cardiol. 2009 Jun 9;53(23):2186-96
references.pmid: 19497447
references.citation: Prev Med. 2009 Aug-Sep;49(2-3):101-7
references.pmid: 19573556
references.citation: Am J Cardiol. 2010 Feb 15;105(4):459-66
references.pmid: 20152239
references.citation: J Am Coll Cardiol. 2010 Sep 14;56(12):946-55
references.pmid: 20828647
references.citation: J Lipid Res. 2010 Nov;51(11):3324-30
references.pmid: 20713651
references.citation: Cell Metab. 2010 Nov 3;12(5):467-82
references.pmid: 21035758
references.citation: Circ Res. 2011 Jan 21;108(2):235-48
references.pmid: 21252151
references.citation: J Am Coll Cardiol. 2011 Apr 12;57(15):1611-21
references.pmid: 21474042
references.citation: Biomark Med. 2011 Oct;5(5):673-94
references.pmid: 22003918
references.citation: Free Radic Biol Med. 2011 Nov 15;51(10):1903-9
references.pmid: 21925592
references.citation: J Am Coll Cardiol. 2012 Jul 10;60(2):112-9
references.pmid: 22766337
references.citation: J Am Coll Cardiol. 2012 Aug 21;60(8):716-21
references.pmid: 22898069
references.citation: Circ Res. 2012 Aug 31;111(6):778-99
references.pmid: 22935534
references.citation: J Lipid Res. 2012 Dec;53(12):2773-90
references.pmid: 22969153
references.citation: J Am Coll Cardiol. 2012 Nov 20;60(21):2218-29
references.pmid: 23122790
references.citation: Atherosclerosis. 2013 Jan;226(1):161-4
references.pmid: 23174369
references.citation: J Am Coll Cardiol. 2013 May 28;61(21):2169-79
references.pmid: 23541965
references.citation: J Lipid Res. 2013 Jul;54(7):1877-83
references.pmid: 23667177
references.citation: Curr Opin Pharmacol. 2013 Apr;13(2):168-79
references.pmid: 23541680
references.citation: J Lipid Res. 2013 Oct;54(10):2815-30
references.pmid: 23828779
references.citation: PLoS One. 2013;8(12):e83145
references.pmid: 24376657
references.citation: Annu Rev Pathol. 2014;9:73-102
references.pmid: 23937439
references.citation: J Am Coll Cardiol. 2014 May 6;63(17):1724-34
references.pmid: 24530664
references.citation: J Am Coll Cardiol. 2014 May 20;63(19):1961-71
references.pmid: 24613321
references.citation: PLoS One. 2014;9(12):e114519
references.pmid: 25531109
references.citation: Circulation. 2004 Jun 29;109(25):3164-70
references.pmid: 15184281
references.citation: J Biol Chem. 2002 Mar 1;277(9):7010-20
references.pmid: 11744722