Received on January 25, 2007
Accepted on May 22, 2007

Lipids, Lipoproteins, and Cardiovascular Risk Factors

Lipoprotein-Associated Phospholipase A₂ Predicts 5-Year Cardiac Mortality Independently of Established Risk Factors and Adds Prognostic Information in Patients with Low and Medium High-Sensitivity C-Reactive Protein (The Ludwigshafen Risk and Cardiovascular Health Study)

¹ Department of Clinical Chemistry, University Medical Center Freiburg, Germany
² Cardiology Group, Frankfurt-Sachsenhausen, Germany
³ LURIC Study Nonprofit LLC, Freiburg, Germany
⁴ Division of Endocrinology, Department of Medicine, University Hospital, Ulm, Germany
⁵ Synlab Center of Laboratory Diagnostics, Heidelberg, Germany

^* To whom correspondence should be addressed. E-mail: kwinkler{at}ukl.uni-freiburg.de.

Background: Lipoprotein-associated phospholipase A₂ (LpPLA₂), also denoted as platelet-activating factor acetylhydrolase, is a lipoprotein-bound enzyme involved in inflammation and atherosclerosis. In this cohort study we investigated LpPLA₂ activity to predict cardiac mortality in patients scheduled for coronary angiography.

Methods: LpPLA₂ activity was determined in 2513 patients with and in 719 patients without angiographically confirmed coronary artery disease (CAD).

Results: During the median observation period of 5.5 years, 501 patients died. In patients with tertiles of LpPLA₂ activity of 420-509 U/L or 510 U/L, unadjusted hazard ratios (HRs) for cardiac death were 1.7 (95% CI 1.3-2.4; P = 0.001), and 1.9 (95% CI 1.4-2.5; P <0.001), respectively, compared with patients with LpPLA₂ activity 419 U/L. After we accounted for established risk factors and included angiographic CAD status, high-sensitivity C-reactive protein (hsCRP), and N-terminal pro-B-type natriuretic peptide, the 3rd tertile of LpPLA₂ activity predicted cardiac 5-year mortality with an HR of 2.0 (95% CI 1.4-3.1; P = 0.001). LpPLA₂ activity increased the adjusted risk for cardiac death by 2-fold in patients with hsCRP <3 mg/L in the 2nd (HR 2.4, 95% CI 1.4-4.2; P = 0.002) and 3rd (HR 2.1, 95% CI 1.1-4.0; P = 0.02) tertiles of LpPLA₂ activity and in patients with hsCRP of 3-10 mg/L in the 3rd tertile (HR 1.9, 95% CI 1.0-3.6; P = 0.03) of LpPLA₂ activity.

Conclusions: LpPLA₂ activity predicts risk for 5-year cardiac mortality independently from established risk factors and indicates risk for cardiac death in patients with low and medium-high hsCRP concentrations. Therefore, LpPLA₂ activity may provide information for the identification and management of patients at risk beyond established risk stratification strategies.