Oxidized Phospholipids on Apolipoprotein B-100 and Recurrent Ischemic Events Following Stroke or Transient Ischemic Attack.
BACKGROUND
Biomarkers to predict recurrent stroke and targets of therapy to prevent stroke are lacking.


OBJECTIVES
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).
['Byun|Young Sup|YS|', 'Yang|Xiaohong|X|', 'Bao|Weihang|W|', 'DeMicco|David|D|', 'Laskey|Rachel|R|', 'Witztum|Joseph L|JL|', 'Tsimikas|Sotirios|S|', '|||']
D000368:Aged D053299:Apolipoprotein B-100 D000069059:Atorvastatin D015415:Biomarkers D008078:Cholesterol, LDL D003324:Coronary Artery Disease D005260:Female D006801:Humans D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors D002546:Ischemic Attack, Transient D053208:Kaplan-Meier Estimate D008297:Male D008875:Middle Aged D010743:Phospholipids D016016:Proportional Hazards Models D012008:Recurrence D055502:Secondary Prevention D020521:Stroke
statin therapy net reclassification improvement integrated discrimination improvement oxidation-specific epitope risk factors