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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1586.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Lipoprotein-Associated Phospholipase A₂ Predicts Future Cardiovascular Events in Patients With Coronary Heart Disease Independently of Traditional Risk Factors, Markers of Inflammation, Renal Function, and Hemodynamic Stress

Wolfgang Koenig; Dorothee Twardella; Hermann Brenner; Dietrich Rothenbacher

From the Department of Internal Medicine II-Cardiology (W.K.), University of Ulm Medical Center, Ulm, Germany; Department of Epidemiology (D.T., H.B., D.R.), German Centre for Research on Ageing at the University of Heidelberg, Heidelberg, Germany.

Correspondence to Wolfgang Koenig, MD, FRCP, FESC, FACC, Department of Internal Medicine II–Cardiology, University of Ulm Medical Center, Robert-Koch Str. 8, D-89081 Ulm, Germany. E-mail wolfgang.koenig{at}medizin.uni-ulm.de

Objectives— We sought to evaluate whether lipoprotein-associated phospholipase A₂ (Lp-PLA₂), an emerging marker of cardiovascular risk, is associated with prognosis in patients with coronary heart disease (CHD).

Methods and Results— Plasma concentrations and activity of Lp-PLA₂ were determined in 1051 patients aged 30 to 70 years with CHD who were followed for &4 years. A Cox proportional hazards model was used to determine the prognostic value of Lp-PLA₂ after adjustment for various covariates, including markers of inflammation, renal function, and hemodynamic stress. In multivariable analyses, Lp-PLA₂ mass and activity were strongly associated with cardiovascular events after controlling for traditional risk factors, severity of CHD, statin treatment, cystatin C, and N-terminal proBNP. The hazard ratio (HR) for recurrent events was 2.65 (95% confidence interval [CI], 1.47 to 4.76) for the top tertile of Lp-PLA₂ mass compared with the bottom tertile and 2.40 (95% CI, 1.35 to 4.29) for Lp-PLA₂ activity. After additional adjustment for low-density lipoprotein (LDL), the HRs were only moderately attenuated (mass: 2.09; 95% CI, 1.10 to 3.96; activity: 1.81; 95% CI, 0.94 to 3.49, respectively), but the latter was no longer statistically significant.

Conclusions— Increased concentrations of Lp-PLA₂ predict future cardiovascular events in patients with manifest CHD independent of a variety of potential risk factors including markers of inflammation, renal function, and hemodynamic stress.

We found that lipoprotein-associated phospholipase A₂ (Lp-PLA₂) strongly predicts secondary cardiovascular events in patients with manifest coronary heart disease (CHD). In multivariable analysis, even including markers of inflammation, renal function, and hemodynamic stress, patients in the top tertile of the Lp-PLA₂ mass and activity distribution showed &2-fold increased risk compared with those in the bottom tertile.

Key Words: cohort study • coronary heart disease • inflammation • lipoprotein-associated phospholipase A₂ pathomechanism • prognosis

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