Lipoprotein-associated Phospholipase A2 and C-reactive Protein for Risk-stratification of Patients with TIA

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 >or=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).

Conclusions: 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.