Lipoprotein-Associated Phospholipase A 2 and C-Reactive Protein for Risk-Stratification of Patients With TIA

Abstract

Background and Purpose— Lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) is a marker of unstable atherosclerotic plaque, and is predictive of both primary and secondary stroke in population-based studies. Methods— We conducted a prospective study of patients with acute TIA who presented to the ED. Clinical risk scoring using the ABCD 2 score was determined and Lp-PLA 2 mass (LpPLA 2 -M) and activity (LpPLA 2 -A) and high-sensitivity C-reactive protein (CRP) were measured. The primary outcome measure was a composite end point consisting of stroke or death within 90 days or identification of a high-risk stroke mechanism requiring specific early intervention (defined as ≥50% stenosis in a vessel referable to symptoms or a cardioembolic source warranting anticoagulation). Results— The composite outcome end point occurred in 41/167 (25%) patients. LpPLA 2 -M levels were higher in end point-positive compared to -negative patients (mean, 192±48 ng/mL versus 175±44 ng/mL, P =0.04). LpPLA 2 -A levels showed similar results (geometric mean, 132 nmol/min/mL, 95% CI 119 to 146 versus 114 nmol/min/mL, 95% CI 108 to 121, P =0.01). There was no relationship between CRP and outcome ( P =0.82). Subgroup analysis showed that both LpPLA 2 -M ( P =0.04) and LpPLA 2 -A ( P =0.06) but not CRP ( P =0.36) were elevated in patients with >50% stenosis. In multivariate analysis using cut-off points defined by the top quartile of each marker, predictors of outcome included LpPLA 2 -A (OR 3.75, 95% CI 1.58 to 8.86, P =0.003) and ABCD 2 score (OR 1.30 per point, 95% CI 0.97 to 1.75, P =0.08). Conclusion— Many patients with TIA have a high-risk mechanism (large vessel stenosis or cardioembolism) or will experience stroke/death within 90 days. In contrast to CRP, both Lp-PLA 2 mass and activity were associated with this composite end point, and LpPLA 2 -A appears to provide additional prognostic information beyond the ABCD 2 clinical risk score alone.