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Effect of perindopril on large artery stiffness and aortic root diameter in patients with Marfan syndrome: a randomized controlled trial.
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- Additional Information
- Source:
Publisher: American Medical Association Country of Publication: United States NLM ID: 7501160 Publication Model: Print Cited Medium: Internet ISSN: 1538-3598 (Electronic) Linking ISSN: 00987484 NLM ISO Abbreviation: JAMA Subsets: MEDLINE
- Publication Information:
Original Publication: Chicago : American Medical Association, 1960-
- Subject Terms:
- Abstract:
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.
- Comments:
Retraction in: JAMA. 2015 Dec 22-29;314(24):2692-3. (PMID: 26594834)
- Molecular Sequence:
ClinicalTrials.gov NCT00485368
- Accession Number:
0 (Adrenergic beta-Antagonists)
0 (Angiotensin-Converting Enzyme Inhibitors)
0 (Transforming Growth Factor beta)
11128-99-7 (Angiotensin II)
EC 3.4.24.17 (Matrix Metalloproteinase 3)
EC 3.4.24.24 (Matrix Metalloproteinase 2)
Y5GMK36KGY (Perindopril)
- Publication Date:
Date Created: 20071004 Date Completed: 20071009 Latest Revision: 20161124
- Publication Date:
20240829
- Accession Number:
10.1001/jama.298.13.1539
- Accession Number:
17911499
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