Oxidized Phospholipids on Apolipoprotein B-100 and Recurrent Ischemic Events Following Stroke or Transient Ischemic Attack

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• 作者：Young Sup Byun ; MD^a ; ^b ; Xiaohong Yang ; BS^a ; Weihang Bao ; PhD^c ; David DeMicco ; PharmD^c ; Rachel Laskey ; PhD^c ; Joseph L. Witztum ; MD^d ; Sotirios Tsimikas ; MD^a ; ^{stsimikas@ucsd.edu} ; for the SPARCL Trial Investigators
• 关键词：integrated discrimination improvement ; net reclassification improvement ; oxidation-specific epitope ; risk factors ; statin therapy
• 刊名：Journal of the American College of Cardiology
• 出版年：2017
• 出版时间：17 January 2017
• 年：2017
• 卷：69
• 期：2
• 页码：147-158
• 全文大小：941 K
• 卷排序：69

文摘

Biomarkers to predict recurrent stroke and targets of therapy to prevent stroke are lacking.ObjectivesThis 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.MethodsIn 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.ResultsPatients 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.ConclusionsElevated 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)