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European Heart Journal Advance Access originally published online on November 19, 2008
European Heart Journal 2009 30(1):107-115; doi:10.1093/eurheartj/ehn502
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Lipoprotein-associated phospholipase A2 activity, ferritin levels, metabolic syndrome, and 10-year cardiovascular and non-cardiovascular mortality: results from the Bruneck study

Sotirios Tsimikas1, Johann Willeit2, Michael Knoflach2, Manuel Mayr6, Georg Egger3, Marlene Notdurfter3, Joseph L. Witztum5, Christian J. Wiedermann4, Qingbo Xu6 and Stefan Kiechl2,*

1 Division of Cardiology, University of California San Diego, La Jolla, CA, USA
2 Department of Neurology, Medical University Innsbruck, Innsbruck, Austria
3 Department of Internal Medicine, Bruneck Hospital, Bruneck, Italy
4 Department of Internal Medicine, Central Hospital of Bolzano, Bolzano, Italy
5 Department of Medicine, University of California San Diego, La Jolla, CA, USA
6 Cardiovascular Division, King's BHF Centre, King's College London, London, UK

Received 16 June 2008; revised 11 September 2008; accepted 16 October 2008; online publish-ahead-of-print 19 November 2008.

* Corresponding author. Tel: +43 512 504 4244, Fax: +43 512 504 4260, Email: stefan.kiechl{at}i-med.ac.at

Aims: To identify factors that influence plasma levels and assess the prognostic value of lipoprotein-associated phospholipase A2 (Lp-PLA2) activity in a prospective, population-based survey of the epidemiology and pathogenesis of atherosclerosis.

Methods and results: The Bruneck study is a prospective, population-based survey initiated in 1990. Lp-PLA2 activity and baseline variables for the current analysis were measured in 765 subjects aged 45–84 years in 1995. Incident cardiovascular disease (CVD) (cardiovascular death, myocardial infarction, stroke, and transient ischaemic attack) and rates of non-CVD mortality were assessed between 1995 and 2005.

Subjects with incident CVD had higher levels of Lp-PLA2 activity (884 ± 196 vs. 771 ± 192 µmol/min/L, P < 0.001). Increased Lp-PLA2 activity was significantly related to incident CVD [age- and sex-adjusted hazard ratio (95%CI) 2.9 (1.6–5.5); third vs. first tertile group; P < 0.001] and with vascular mortality but not with non-CVD mortality. Lp-PLA2 activity was enhanced in subjects with the metabolic syndrome and showed highly significant positive associations with LDL-C, apoB-100, ferritin, and HOMA-IR, and inverse associations with HDL-C and anti-oxidant levels.

Conclusion: Increased Lp-PLA2 activity is associated with metabolic syndrome and incident fatal and non-fatal CVD, but not with non-CVD mortality. Furthermore, Lp-PLA2 activity is strongly influenced by ferritin levels, LDL-C, and apoB-100 supporting its integral role in lipid peroxidation. Clinical utility of Lp-PLA2 activity for prediction of cardiovascular risk has to be explored in future studies.

Key Words: Lipoprotein-associated phospholipase A2 • Myocardial infarction • Oxidation • Atherosclerosis • Anti-oxidants


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