title: Oxidized Phospholipids on Apolipoprotein B-100 and Recurrent Ischemic Events Following Stroke or Transient Ischemic Attack.
abstract: BACKGROUND
  Biomarkers to predict recurrent stroke and targets of therapy to prevent stroke are lacking.
  
  
  OBJECTIVE
  This study evaluated whether patients with prior cerebrovascular events and elevated levels of oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB), but without prior coronary artery disease (CAD), are at risk for recurrent stroke and CAD events following high-dose statin therapy.
  
  
  METHODS
  In the SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) trial, OxPL-apoB levels were measured in 4,385 patients with stroke or transient ischemic attack at baseline and in 3,106 patients at 5 years following randomization to placebo or 80 mg atorvastatin. The primary endpoint was the time from randomization to a second nonfatal or fatal stroke. Secondary endpoints included first major coronary events and any cardiovascular event.
  
  
  RESULTS
  Patients with recurrent stroke had higher baseline median OxPL-apoB levels than patients without (15.5 nmol/l vs. 11.6 nmol/l; p < 0.0001). After multivariable adjustment, elevated baseline OxPL-apoB predicted recurrent stroke (hazard ratio [HR]: 4.3; p < 0.0001), first major coronary events (HR: 4.0; p < 0.0001), and any cardiovascular event (HR: 4.4; p < 0.0001). These comparisons for any endpoint did not differ by treatment, shown as a nonsignificant interaction test. The net reclassification improvement, integrated discrimination improvement, and area under the receiver-operating characteristic curve (AUC) were all significantly improved by adding OxPL-apoB to the models, with ΔAUC +0.0505 (p < 0.0001) for recurrent stroke, ΔAUC +0.0409 (p < 0.0001) for first major coronary event, and ΔAUC +0.0791 (p < 0.0001) for any cardiovascular event.
  
  
  CONCLUSIONS
  Elevated OxPL-apoB levels predicted recurrent stroke and first major coronary events in patients with prior stroke or transient ischemic attack. The lack of statin-OxPL-apoB treatment interaction suggested that OxPLs might be statin-independent therapeutic targets to reduce risk of cardiovascular events. (Lipitor in the Prevention of Stroke, for Patients Who Have Had a Previous Stroke [SPARCL]; NCT00147602).
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, Republic of 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.
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 / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood* / Q000517:prevention & control*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D002546:Ischemic Attack, Transient / Q000097:blood* / Q000517:prevention & control*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010743:Phospholipids / Q000097:blood*; D016016:Proportional Hazards Models; D012008:Recurrence; D055502:Secondary Prevention; D020521:Stroke / Q000097:blood* / Q000517:prevention & control*
chemical_list: D053299:Apolipoprotein B-100; D015415:Biomarkers; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010743:Phospholipids; D000069059:Atorvastatin
keywords: integrated discrimination improvement; net reclassification improvement; oxidation-specific epitope; risk factors; statin therapy