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Journal of Lipid Research, Vol. 50, 723-729, April 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Patient-Oriented and Epidemiological Research

PLTP activity is a risk factor for subsequent cardiovascular events in CAD patients under statin therapy: the AtheroGene Study

Axel Schlitt^1,*, Stefan Blankenberg, Christoph Bickel, Karl J. Lackner, Gunnar H. Heine^**, Michael Buerke^*, Karl Werdan^*, Lars Maegdefessel^*, Uwe Raaz^*, Hans J. Rupprecht, Thomas Munzel and Xian-Cheng Jiang

^* Department of Medicine III, Martin Luther-University Halle-Wittenberg, Germany
Department of Medicine II and Institute of Clinical Chemistry and Laboratory Medicine, Johannes Gutenberg-University Mainz, Germany
Hospital of the German Federal Armed Forces, Koblenz, Germany
^** Department of Medicine IV, University of the Saarland, Homburg/Saar, Germany
GPR Clinic, Ruesselsheim, Germany
Department of Anatomy and Cell Biology, State University of New York, Downstate Medical Center Brooklyn, New York, NY

Published, JLR Papers in Press, November 10, 2008.

This work was partially supported by grants HL69817 and AHA Grant-in-Aid (0755922T). Competing interests: The authors declare that they have no competing interests. All authors have made substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data. All authors have been involved in drafting the manuscript or revising it critically for important intellectual content, and have given final approval of the version to be published.

¹ To whom correspondence should be addressed. e-mail: axel.schlitt{at}medizin.uni-halle.de

Phospholipid transferprotein (PLTP) mediates both net transfer and exchange of phospholipids between different lipoproteins. Although many studies have investigated the role of PLTP in atherogenesis, the role of PLTP in atherosclerotic diseases is unclear. We investigated the association of serum PLTP activity with the incidence of a combined endpoint (myocardial infarction and cardiovascular death) and its relation to other markers of atherosclerosis in 1,085 patients with angiographically documented coronary artery disease (CAD). In the median follow-up of 5.1 years, 156 patients had suffered from the combined endpoint of myocardial infarction or cardiovascular death including 47 of 395 patients who were on statins at baseline. In Kaplan-Meyer analyses serum PLTP activity was not associated with the combined endpoint in all patients. However, in the subgroup of patients receiving statins at baseline, PLTP was shown to be a significant predictor of cardiovascular outcome (P = 0.019), and this also remained stable in univariate (P = 0.027) and multivariate cox regression analyses (P = 0.041) including potential confounders (classical risk factors, HDL cholesterol (HDL-C), and others). We showed in our study that, under statin treatment, high plasma PLTP activity was related to fatal and nonfatal cardiovascular events in CAD patients.

Supplementary key words lipid transfer proteins • atherosclerosis • 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors

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