Key result
Elevated oxidized phospholipids on apoB-100 linked to ~4.3-fold higher recurrent stroke risk.
Why the study?
Biomarkers to predict recurrent stroke and targets of therapy to prevent stroke are lacking in patients with prior cerebrovascular events without prior CAD.
Does elevated baseline oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB) predict recurrent stroke and cardiovascular events in patients with prior stroke or transient ischemic attack?
RCT (n=4,385)
randomized
Does elevated baseline oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB) predict recurrent stroke and cardiovascular events in patients with prior stroke or transient ischemic attack?
Elevated baseline OxPL-apoB is a strong, statin-independent predictor of recurrent stroke and major coronary events in patients with a history of stroke or TIA.
Answers are grounded in this paper and cite their sources.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“In this case, there is potential for all 3 applications. The first has already been achieved. But, more importantly, the molecularly discrete oxidation-specific epitopes offered by oxidized phospholipids suggest both targets for therapy and for molecular diagnostics.”
“Circulating biomarkers selected for their role in inflammation or oxidative stress were found associated with cerebrovascular outcomes in SPARCL, but these biomarkers had been selected based on their known association with coronary events and thus lacked specificity for stroke. Thus, elevated plasma levels of oxidized phospholipids on apoB100 (apolipoproteinB100) containing lipoproteins equally predicted recurrent strokes and incident coronary events in SPARCL.”
Elevated OxPL-apoB predicted recurrent stroke and CAD events; leaves open whether it identifies statin-independent targets or warrants prospective validation.
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).
No takes yet. Share an insight, caveat, or question.
Byun et al. (2017) conducted an RCT in Prior stroke or transient ischemic attack without prior coronary artery disease (n=4,385). Elevated oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB) vs. Lower or non-elevated OxPL-apoB levels was evaluated on Time from randomization to a second nonfatal or fatal stroke (HR 4.3, p=<0.0001). Elevated baseline oxidized phospholipids on apolipoprotein B-100 strongly predicted recurrent stroke (HR 4.3; P<0.0001), independent of high-dose statin therapy.
Synapse has enriched 5 related papers. Consider them for comparative context: