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European Heart Journal Advance Access published online on June 18, 2008
European Heart Journal, doi:10.1093/eurheartj/ehn276
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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

Impact of a combined treatment of angiotensin II type 1 receptor blockade and 3-hydroxy-3-methyl-glutaryl-CoA-reductase inhibition on secretory phospholipase A2-type IIA and low density lipoprotein oxidation in patients with coronary artery disease

Dimitar Divchev1, Christina Grothusen1, Maren Luchtefeld1, Martin Thoenes2,3, Frederick Onono4, Rainer Koch5, Helmut Drexler1 and Bernhard Schieffer1,*

1 Department of Cardiology and Angiology, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany
2 Sanofi-Aventis, Paris, France
3 Institute for Clinical Pharmacology, Technische Universitaet, Dresden, Germany
4 Department of Haematology, Haemostasis, and Oncology, Medizinische Hochschule Hannover, Germany
5 Institute for Biostatistics, Technische Universitaet Dresden, Germany

Received 23 May 2007; revised 19 May 2008; accepted 5 June 2008.

* Corresponding author. Tel: +49 511 532 2129, Fax: +49 511 532 3357. Email: schieffer.bernhard{at}mh-hannover.de

Aims: To evaluate the impact of a combined treatment of angiotensin II type 1 (AT1)-receptor blockade and 3-hydroxy-3-methyl-glutaryl-CoA-reductase inhibition (statin) on the secretory phospholipase A2 type IIA (sPLA2-IIA) and oxidized low density lipoprotein (oxLDL) in patients with coronary artery disease (CAD).

Methods and results: Sixty patients with angiographically documented CAD and a history of arterial hypertension were randomized in a double-blinded fashion to pravastatin (PRAV, 40 mg/day, n = 30) or PRAV plus irbesartan (PRAV+IRB, 40 mg/day+300 mg/day, n = 30) and were treated for 3 months. Blood pressure (BP) and cholesterol fractions were determined at baseline and after 3 months. SPLA2 activity as primary endpoint, sPLA2-IIA protein, oxLDL levels, and high-sensitivity (hs)-C-reactive protein were measured by an enzyme-linked immunabsorbent assay. In both treatment groups, systolic BP levels and circulating HDL and LDL levels were reduced to the same extent. The combined treatment of PRAV+IRB significantly decreased sPLA2-IIA activity and sPLA2-IIA-protein concentration compared with PRAV treatment alone (P < 0.05). In addition, PRAV+IRB significantly reduced oxLDL levels compared with PRAV treatment alone (P < 0.05). This effect was independent of changes in LDL cholesterol levels.

Conclusion: These findings are consistent with the notion that the combined treatment of pravastatin with irbesartan reduced sPLA2-IIA-activity, sPLA2-IIA-protein concentration, and oxLDL in patients with CAD suggesting a novel anti-atherogenic effect by combining AT1-receptor blockade with statin treatment.

Key Words: AT1-receptor blockade • Statin • oxLDL • sPLA2-IIA • CAD


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