|Effect of perindopril on large artery stiffness and aortic root diameter in patients with Marfan syndrome: a randomized controlled trial.|
|PMID: 17911499 Owner: NLM Status: MEDLINE|
|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  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  mm Hg to 80  mm Hg in perindopril group vs 83  mm Hg to 84  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  ng/mL to 45  ng/mL in perindopril group, P = .01 vs placebo) and active (46  ng/mL to 42  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.
|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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|Type: Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't|
|Title: JAMA Volume: 298 ISSN: 1538-3598 ISO Abbreviation: JAMA Publication Date: 2007 Oct|
|Created Date: 2007-10-03 Completed Date: 2007-10-09 Revised Date: 2014-09-17|
Medline Journal Info:
|Nlm Unique ID: 7501160 Medline TA: JAMA Country: United States|
|Languages: eng Pagination: 1539-47 Citation Subset: AIM; IM|
|Data Bank Information|
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Angiotensin II / antagonists & inhibitors
Angiotensin-Converting Enzyme Inhibitors / pharmacology, therapeutic use*
Aorta / drug effects, pathology, ultrasonography
Arteries / drug effects*, physiology*, ultrasonography
Blood Flow Velocity
Marfan Syndrome / drug therapy*, physiopathology*, ultrasonography
Matrix Metalloproteinase 2 / blood
Matrix Metalloproteinase 3 / blood
Perindopril / pharmacology, therapeutic use*
Transforming Growth Factor beta / blood
Vasodilation / drug effects*
|0/Adrenergic beta-Antagonists; 0/Angiotensin-Converting Enzyme Inhibitors; 0/Transforming Growth Factor beta; 11128-99-7/Angiotensin II; EC 184.108.40.206/Matrix Metalloproteinase 3; EC 220.127.116.11/Matrix Metalloproteinase 2; Y5GMK36KGY/Perindopril|
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