Document Detail


Effect of perindopril on large artery stiffness and aortic root diameter in patients with Marfan syndrome: a randomized controlled trial.
MedLine Citation:
PMID:  17911499     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CONTEXT: Aortic stiffness is increased in Marfan syndrome contributing to aortic dilatation and rupture, the major cause of premature death in this population. Angiotensin-converting enzyme inhibitors have been shown to reduce arterial stiffness. OBJECTIVE: To determine whether perindopril therapy reduces aortic stiffness and attenuates aortic dilatation in patients with Marfan syndrome. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled trial of 17 patients with Marfan syndrome (mean [SD], 33 [6] years) taking standard beta-blocker therapy, initiated in January 2004 and completed in September 2006, at Alfred Hospital Marfan Syndrome Clinic, Melbourne, Australia. INTERVENTION: Patients were administered 8 mg/d of perindopril (n = 10) or placebo (n = 7) for 24 weeks. MAIN OUTCOME MEASURES: Indices of arterial stiffness were assessed via systemic arterial compliance, and central and peripheral pulse wave velocities. Aortic root diameters were assessed at 4 sites via transthoracic echocardiography. RESULTS: Perindopril reduced arterial stiffness as indicated by increased systemic arterial compliance (mean [SEM], 0.33 [0.01] mL/mm Hg at baseline to 0.54 [0.04] mL/mm Hg at 24 weeks in perindopril group vs 0.30 [0.01] mL/mm Hg to 0.29 [0.01] mL/mm Hg in placebo group, P = .004), and reduced central (7.6 [0.4] m/s to 5.9 [0.3] m/s in perindopril group, P < .001 vs placebo) and peripheral (10.9 [0.4] m/s to 8.7 [0.4] m/s in perindopril group, P < .001 vs placebo) pulse wave velocities. In addition, perindopril significantly reduced aortic root diameters relative to placebo in both end-systole and end-diastole (P<.01 to P < .001 for all comparisons between groups). Although perindopril marginally reduced mean arterial pressure (from 81 [2] mm Hg to 80 [1] mm Hg in perindopril group vs 83 [2] mm Hg to 84 [3] mm Hg in placebo group, P = .004), the observed changes in both stiffness and left ventricular outflow tract diameter remained significant when mean arterial pressure was included as a covariate. Transforming growth factor beta (TGF-beta), which contributes to aortic degeneration in Marfan syndrome, was reduced by perindopril compared with placebo in both latent (59 [6] ng/mL to 45 [3] ng/mL in perindopril group, P = .01 vs placebo) and active (46 [2] ng/mL to 42 [1] ng/mL in perindopril group, P = .02 vs placebo) forms. CONCLUSIONS: Perindopril reduced both aortic stiffness and aortic root diameter in patients with Marfan syndrome taking standard beta-blocker therapy, possibly through attenuation of TGF-beta signaling. Large clinical trials are needed to assess the clinical benefit of angiotensin II blockade in Marfan syndrome. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00485368.
Authors:
Anna A Ahimastos; Anuradha Aggarwal; Kellie M D'Orsa; Melissa F Formosa; Anthony J White; Ravi Savarirayan; Anthony M Dart; Bronwyn A Kingwell
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  JAMA : the journal of the American Medical Association     Volume:  298     ISSN:  1538-3598     ISO Abbreviation:  JAMA     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-10-03     Completed Date:  2007-10-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7501160     Medline TA:  JAMA     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1539-47     Citation Subset:  AIM; IM    
Affiliation:
Alfred and Baker Medical Unit, Baker Heart Research Institute, Central Melbourne, Victoria, Australia.
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00485368
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MeSH Terms
Descriptor/Qualifier:
Adrenergic beta-Antagonists / therapeutic use*
Adult
Angiotensin II / antagonists & inhibitors
Angiotensin-Converting Enzyme Inhibitors / pharmacology,  therapeutic use*
Aorta / drug effects,  pathology,  ultrasonography
Arteries / drug effects*,  physiology*,  ultrasonography
Blood Flow Velocity
Blood Pressure
Double-Blind Method
Echocardiography
Female
Humans
Male
Marfan Syndrome / drug therapy*,  physiopathology*,  ultrasonography
Matrix Metalloproteinase 2 / blood
Matrix Metalloproteinase 3 / blood
Perindopril / pharmacology,  therapeutic use*
Transforming Growth Factor beta / blood
Ultrasonography, Doppler
Vasodilation / drug effects*
Chemical
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 0/Angiotensin-Converting Enzyme Inhibitors; 0/Transforming Growth Factor beta; 11128-99-7/Angiotensin II; 82834-16-0/Perindopril; EC 3.4.24.17/Matrix Metalloproteinase 3; EC 3.4.24.24/Matrix Metalloproteinase 2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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