title: Vascular function and atherosclerosis progression after 1 y of flavonoid intake in statin-treated postmenopausal women with type 2 diabetes: a double-blind randomized controlled trial.
abstract: BACKGROUND
  In healthy participants, short-term flavan-3-ol and isoflavone intakes improve vascular function; however, the potential combined benefit of these compounds on atherosclerosis progression remains unclear for those at elevated risk of cardiovascular disease.
  
  
  OBJECTIVE
  The objective was to examine whether combined isoflavone and flavan-3-ol intake alters vascular function in postmenopausal women with type 2 diabetes mellitus (T2DM).
  
  
  METHODS
  A double-blind, parallel-design, placebo-controlled 1-y trial was conducted in postmenopausal T2DM patients randomly assigned to a split dose of 27 g flavonoid-enriched chocolate/d [850 mg flavan-3-ols (90 mg epicatechin) + 100 mg isoflavones (aglycone equivalents)/d] or matched placebo. Intima-media thickness of the common carotid artery (CCA-IMT), pulse wave velocity (PWV), augmentation index, blood pressure (BP), and vascular biomarkers were assessed.
  
  
  RESULTS
  A total of 93 patients completed the trial. Overall, the flavonoid intervention did not significantly change CCA-IMT, augmentation index, or BP, but pulse pressure variability improved (flavonoid: -0.11 ± 0.07 mm Hg/min; placebo: 0.10 ± 0.11 mm Hg/min; P = 0.04). In a subgroup with PWV data, net improvements were observed [flavonoid (n = 18): -0.07 ± 0.38 m/s; placebo (n = 17): 0.68 ± 0.25 m/s; P = 0.01], which equated to a 10% CV risk reduction. Equol producers (n = 17) had larger reductions in diastolic BP, mean arterial pressure, and PWV (-2.24 ± 1.31 mm Hg, -1.24 ± 1.30 mm Hg, and -0.68 ± 0.40 m/s, respectively; P < 0.01) compared with non-equol producers (n = 30).
  
  
  CONCLUSIONS
  Although the 1-y intervention did not change CCA-IMT or BP, clinically relevant improvements in arterial stiffness were observed; equol producers were particularly responsive. Flavonoids may augment existing therapeutic strategies to reduce cardiovascular disease risk in postmenopausal T2DM patients, and longer studies are needed to examine the effects on atherosclerosis progression. This trial was registered at clinicaltrials.gov as NCT00677599.
authors.affiliation: Departments of Nutrition and Radiology Department, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, United Kingdom.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Curtis
authors.forename: John
authors.initials: J
authors.lastname: Potter
authors.forename: Paul A
authors.initials: PA
authors.lastname: Kroon
authors.forename: Paddy
authors.initials: P
authors.lastname: Wilson
authors.forename: Ketan
authors.initials: K
authors.lastname: Dhatariya
authors.forename: Mike
authors.initials: M
authors.lastname: Sampson
authors.forename: Aedín
authors.initials: A
authors.lastname: Cassidy
mesh_terms: D000368:Aged; D062186:Arterial Pressure / Q000187:drug effects; D050197:Atherosclerosis / Q000188:drug therapy* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D017536:Carotid Artery, Common / Q000187:drug effects; D059168:Carotid Intima-Media Thickness; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004032:Diet; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007529:Isoflavones / Q000008:administration & dosage*; D008875:Middle Aged; D010349:Patient Compliance; D017698:Postmenopause; D063177:Pulse Wave Analysis; D059289:Vascular Stiffness / Q000187:drug effects
chemical_list: D015415:Biomarkers; D005419:Flavonoids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007529:Isoflavones; C404987:flavan-3-ol