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European Heart Journal Advance Access originally published online on August 7, 2009
European Heart Journal 2009 30(22):2742-2748; doi:10.1093/eurheartj/ehp302
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org

Association between type II secretory phospholipase A2 plasma concentrations and activity and cardiovascular events in patients with coronary heart disease

Wolfgang Koenig1,*, Carla Y. Vossen2, Ziad Mallat3, Hermann Brenner2, Joëlle Benessiano3 and Dietrich Rothenbacher2

1 Department of Internal Medicine II-Cardiology, University of Ulm Medical Center, Albert-Einstein-Allee 23, D-89081 Ulm, Germany
2 Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany
3 Inserm U689, Hopital Lariboisiere, Paris, France

Received 5 September 2008; revised 4 May 2009; accepted 16 June 2009; online publish-ahead-of-print 7 August 2009.

* Corresponding author. Tel: +49 731 500 45001, Fax: +49 731 500 45021, Email: wolfgang.koenig{at}uniklinik-ulm.de

Aims: Type II secretory phospholipase A2 (sPLA2-IIA) is widely expressed in various cell types and may trigger local inflammatory responses. We sought to evaluate whether systemic sPLA2 is associated with prognosis in patients with coronary heart disease (CHD).

Methods and results: Plasma concentrations of sPLA2 (ELISA) and sPLA2 activity (selective fluorometric assay) were measured at baseline in a cohort of 1024 patients aged 30–70 years with CHD. The Cox-proportional hazards model was used to determine the prognostic value of sPLA2 on a combined cardiovascular disease (CVD) endpoint after adjustment for covariates. During a mean follow-up of 4.1 years, 93 patients (9.1%) experienced a secondary CVD event. In a multivariable model, sPLA2 mass and activity were associated with hazard ratios of secondary CVD events of 2.07 (95% CI, 1.17–3.66) and 1.65 (95% CI 0.96–2.84) for mass and activity, respectively, when extreme tertiles were compared. Further adjustment for cystatin C, N-terminal-probrain natriuretic peptide, C-reactive protein, and lipoprotein-associated phospholipase A2 attenuated the associations, still showing a positive trend for mass but a less clear pattern for activity. However, when sPLA2 mass and activity were analysed as continuous variables both still showed a statistically significant increase in risk in all models.

Conclusion: Secretory phospholipase A2 mass and activity appear to be predictive of secondary CVD events in patients with CHD.

Key Words: Coronary heart disease • Type IIA secretory phospholipase A2 • Prognosis • Cohort study • Pathomechanism • Inflammation


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