on April 20, 2006
Published online before print April 20, 2006, doi: 10.1161/01.ATV.0000222983.73369.c8
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Submitted on February 22, 2005
Accepted on April 6, 2006
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 *;
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.
* To whom correspondence should be addressed. 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.
Key words: cohort study • coronary heart disease • inflammation • lipoprotein-associated phospholipase A2 pathomechanism • prognosis
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