title: Effects of Pycnogenol on endothelial function in patients with stable coronary artery disease: a double-blind, randomized, placebo-controlled, cross-over study.
abstract: OBJECTIVE
  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.
  
  
  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-F(2t)-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.
  
  
  CONCLUSIONS
  This study provides the first evidence that the antioxidant Pycnogenol improves endothelial function in patients with CAD by reducing oxidative stress.
authors.affiliation: Cardiovascular Center Cardiology, University Hospital Zürich, Rämistrasse 100, Zürich, Switzerland. frank.enseleit@usz.ch
authors.forename: Frank
authors.initials: F
authors.lastname: Enseleit
authors.forename: Isabella
authors.initials: I
authors.lastname: Sudano
authors.forename: Daniel
authors.initials: D
authors.lastname: Périat
authors.forename: Stephan
authors.initials: S
authors.lastname: Winnik
authors.forename: Mathias
authors.initials: M
authors.lastname: Wolfrum
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Flammer
authors.forename: Georg M
authors.initials: GM
authors.lastname: Fröhlich
authors.forename: Priska
authors.initials: P
authors.lastname: Kaiser
authors.forename: Astrid
authors.initials: A
authors.lastname: Hirt
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Haile
authors.forename: Nazmi
authors.initials: N
authors.lastname: Krasniqi
authors.forename: Christian M
authors.initials: CM
authors.lastname: Matter
authors.forename: Klaus
authors.initials: K
authors.lastname: Uhlenhut
authors.forename: Petra
authors.initials: P
authors.lastname: Högger
authors.forename: Michel
authors.initials: M
authors.lastname: Neidhart
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Lüscher
authors.forename: Frank
authors.initials: F
authors.lastname: Ruschitzka
authors.forename: Georg
authors.initials: G
authors.lastname: Noll
mesh_terms: D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D000959:Antihypertensive Agents / Q000008:administration & dosage; D000975:Antioxidants / Q000008:administration & dosage*; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000503:physiopathology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D019332:Endothelin-1 / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts; D011446:Prospective Studies; D033081:Shear Strength; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage
chemical_list: D000893:Anti-Inflammatory Agents; D000959:Antihypertensive Agents; D000975:Antioxidants; D015415:Biomarkers; D019332:Endothelin-1; D005419:Flavonoids; D010936:Plant Extracts; D014665:Vasodilator Agents; C487735:dimethylarginine; C024070:pycnogenols; D002097:C-Reactive Protein; D001120:Arginine