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Effects of Pycnogenol on endothelial function in patients with stable coronary artery disease: a double-blind, randomized, placebo-controlled, cross-over study

Enseleit, Frank ; Sudano, Isabella ; Périat, Daniel ; Winnik, Stephan ; Wolfrum, Mathias ; Flammer, Andreas J. ; Fröhlich, Georg M. ; Kaiser, Priska ; Hirt, Astrid ; Haile, Sarah R. ; Krasniqi, Nazmi ; Matter, Christian M. ; Uhlenhut, Klaus ; Högger, Petra ; Neidhart, Michel ; Lüscher, Thomas F. ; Ruschitzka, Frank ; Noll, Georg

In: European Heart Journal, 2012, vol. 33, no. 13, p. 1589-1597

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    Title
    • Effects of Pycnogenol on endothelial function in patients with stable coronary artery disease: a double-blind, randomized, placebo-controlled, cross-over study
    Author
    • Enseleit, Frank. Cardiovascular Center Cardiology, University Hospital Zürich, Rämistrasse 100, 8091 Zürich, Switzerland
    • Sudano, Isabella. Cardiovascular Center Cardiology, University Hospital Zürich, Rämistrasse 100, 8091 Zürich, Switzerland
    • Périat, Daniel. Cardiovascular Center Cardiology, University Hospital Zürich, Rämistrasse 100, 8091 Zürich, Switzerland
    • Winnik, Stephan. Cardiovascular Center Cardiology, University Hospital Zürich, Rämistrasse 100, 8091 Zürich, Switzerland
    • Wolfrum, Mathias. Cardiovascular Center Cardiology, University Hospital Zürich, Rämistrasse 100, 8091 Zürich, Switzerland
    • Flammer, Andreas J.. Cardiovascular Center Cardiology, University Hospital Zürich, Rämistrasse 100, 8091 Zürich, Switzerland
    • Fröhlich, Georg M.. Cardiovascular Center Cardiology, University Hospital Zürich, Rämistrasse 100, 8091 Zürich, Switzerland
    • Kaiser, Priska. Cardiovascular Center Cardiology, University Hospital Zürich, Rämistrasse 100, 8091 Zürich, Switzerland
    • Hirt, Astrid. Cardiovascular Center Cardiology, University Hospital Zürich, Rämistrasse 100, 8091 Zürich, Switzerland
    • Haile, Sarah R.. Biostatistics Unit, Institute for Social and Preventive Medicine, University of Zürich, Zürich, Switzerland
    • Krasniqi, Nazmi. Cardiovascular Center Cardiology, University Hospital Zürich, Rämistrasse 100, 8091 Zürich, Switzerland
    • Matter, Christian M.. Cardiovascular Center Cardiology, University Hospital Zürich, Rämistrasse 100, 8091 Zürich, Switzerland
    • Uhlenhut, Klaus. Institute of Pharmacy and Food Chemistry, University of Würzburg, Würzburg, Germany
    • Högger, Petra. Institute of Pharmacy and Food Chemistry, University of Würzburg, Würzburg, Germany
    • Neidhart, Michel. Department of Rheumatology, University Hospital Zürich, Zürich, Switzerland
    • Lüscher, Thomas F.. Cardiovascular Center Cardiology, University Hospital Zürich, Rämistrasse 100, 8091 Zürich, Switzerland
    • Ruschitzka, Frank. Cardiovascular Center Cardiology, University Hospital Zürich, Rämistrasse 100, 8091 Zürich, Switzerland
    • Noll, Georg. Cardiovascular Center Cardiology, University Hospital Zürich, Rämistrasse 100, 8091 Zürich, Switzerland
    Document Type
    • Postprint
    OAI-PMH Identifier
    • oai:doc.rero.ch:299187
    Summary
    Aims Extracts from pine tree bark containing a variety of flavonoids have been used in traditional medicine. Pycnogenol is a proprietary bark extract of the French maritime pine tree (Pinus pinaster ssp. atlantica) that exerts antioxidative, anti-inflammatory, and anti-platelet effects. However, the effects of Pycnogenol on endothelial dysfunction, a precursor of atherosclerosis and cardiovascular events, remain still elusive. Methods and results Twenty-three patients with coronary artery disease (CAD) completed this randomized, double-blind, placebo-controlled cross-over study. Patients received Pycnogenol (200 mg/day) for 8 weeks followed by placebo or vice versa on top of standard cardiovascular therapy. Between the two treatment periods, a 2-week washout period was scheduled. At baseline and after each treatment period, endothelial function, non-invasively assessed by flow-mediated dilatation (FMD) of the brachial artery using high-resolution ultrasound, biomarkers of oxidative stress and inflammation, platelet adhesion, and 24 h blood pressure monitoring were evaluated. In CAD patients, Pycnogenol treatment was associated with an improvement of FMD from 5.3 ± 2.6 to 7.0 ± 3.1 (P < 0.0001), while no change was observed with placebo (5.4 ± 2.4 to 4.7 ± 2.0; P = 0.051). This difference between study groups was significant [estimated treatment effect 2.75; 95% confidence interval (CI): 1.75, 3.75, P < 0.0001]. 15-F2t-Isoprostane, an index of oxidative stress, significantly decreased from 0.71 ± 0.09 to 0.66 ± 0.13 after Pycnogenol treatment, while no change was observed in the placebo group (mean difference 0.06 pg/mL with an associated 95% CI (0.01, 0.11), P = 0.012]. Inflammation markers, platelet adhesion, and blood pressure did not change after treatment with Pycnogenol or placebo. Conclusion This study provides the first evidence that the antioxidant Pycnogenol improves endothelial function in patients with CAD by reducing oxidative stress. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT00641758