Effects of resveratrol on aortic growth in patients with Marfan syndrome: a single-arm open-label multicentre trial.

Aneurysm, Dissecting Aortic Aneurysm Magnetic Resonance Imaging Marfan Syndrome Pharmacology, Clinical

Journal

Heart (British Cardiac Society)
ISSN: 1468-201X
Titre abrégé: Heart
Pays: England
ID NLM: 9602087

Informations de publication

Date de publication:
24 Sep 2024
Historique:
received: 24 04 2024
accepted: 06 09 2024
medline: 25 9 2024
pubmed: 25 9 2024
entrez: 24 9 2024
Statut: aheadofprint

Résumé

Resveratrol, a dietary supplement that intervenes in cellular metabolism, has been shown to reduce aortic growth rate in a mouse model of Marfan syndrome (MFS), a condition associated in humans with life-threatening aortic complications, often preceded by aortic dilatation. The primary objective of this study was to investigate the effects of resveratrol on aortic growth rate in patients with MFS . In this investigator-initiated, single-arm open-label multicentre trial, we analysed resveratrol treatment in adults aged 18-50 years with MFS. The primary endpoint was the change in estimated annual aortic growth at five predefined levels in the thoracic aorta after 1 year of resveratrol treatment, evaluated using a linear mixed model. Aortic diameters were measured by cardiac MRI at three time points to analyse the annual aortic expansion rate before and after initiation of treatment. Additionally, annual aortic growth was compared with growth in a previously conducted losartan randomised clinical trial. 898 patients were screened of which 19% (168/898) patients met the inclusion criteria.36% (61/168) patients signed informed consent and 93% (57/61) aged 37±9 years, of which 28 males (49%) were included in the final analysis of the study. 46% (26/57) had undergone aortic root replacement prior to the study. Aortic root diameters remained stable after 1.2±0.3 years of resveratrol administration. A trend towards a decrease in estimated growth rate (mm/year) was observed in the aortic root (from 0.39±0.06 to -0.13±0.23, p=0.072), ascending aorta (from 0.40±0.05 to -0.01±0.18, p=0.072) and distal descending aorta (from 0.32±0.04 to 0.01±0.14, p=0.072). Resveratrol treatment for 1 year may stabilise the aortic growth rate in adult patients with MFS. However, a subsequent randomised clinical trial with a longer follow-up duration and a larger study cohort is needed to establish an actual long-term beneficial effect of this dietary supplement in patients with MFS. NL66127.018.18.

Sections du résumé

BACKGROUND BACKGROUND
Resveratrol, a dietary supplement that intervenes in cellular metabolism, has been shown to reduce aortic growth rate in a mouse model of Marfan syndrome (MFS), a condition associated in humans with life-threatening aortic complications, often preceded by aortic dilatation. The primary objective of this study was to investigate the effects of resveratrol on aortic growth rate in patients with MFS .
METHODS METHODS
In this investigator-initiated, single-arm open-label multicentre trial, we analysed resveratrol treatment in adults aged 18-50 years with MFS. The primary endpoint was the change in estimated annual aortic growth at five predefined levels in the thoracic aorta after 1 year of resveratrol treatment, evaluated using a linear mixed model. Aortic diameters were measured by cardiac MRI at three time points to analyse the annual aortic expansion rate before and after initiation of treatment. Additionally, annual aortic growth was compared with growth in a previously conducted losartan randomised clinical trial.
RESULTS RESULTS
898 patients were screened of which 19% (168/898) patients met the inclusion criteria.36% (61/168) patients signed informed consent and 93% (57/61) aged 37±9 years, of which 28 males (49%) were included in the final analysis of the study. 46% (26/57) had undergone aortic root replacement prior to the study. Aortic root diameters remained stable after 1.2±0.3 years of resveratrol administration. A trend towards a decrease in estimated growth rate (mm/year) was observed in the aortic root (from 0.39±0.06 to -0.13±0.23, p=0.072), ascending aorta (from 0.40±0.05 to -0.01±0.18, p=0.072) and distal descending aorta (from 0.32±0.04 to 0.01±0.14, p=0.072).
CONCLUSION CONCLUSIONS
Resveratrol treatment for 1 year may stabilise the aortic growth rate in adult patients with MFS. However, a subsequent randomised clinical trial with a longer follow-up duration and a larger study cohort is needed to establish an actual long-term beneficial effect of this dietary supplement in patients with MFS.
TRIAL REGISTRATION NUMBER BACKGROUND
NL66127.018.18.

Identifiants

pubmed: 39317438
pii: heartjnl-2024-324343
doi: 10.1136/heartjnl-2024-324343
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: None declared.

Auteurs

Mitzi Marlotte van Andel (MM)

Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.
Cardiology, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands.

Daan Bosshardt (D)

Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.
Cardiology, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands.
Radiology and Nuclear Medicine, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands.

Eric M Schrauben (EM)

Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.
Radiology and Nuclear Medicine, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands.

Renske Merton (R)

Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.
Radiology and Nuclear Medicine, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands.

Roland R L van Kimmenade (RRL)

Cardiology, Radboud University Medical Center, Nijmegen, The Netherlands.

Arthur Scholte (A)

Cardiology, Leiden University Medical Center, Leiden, The Netherlands.

Michael G Dickinson (MG)

Cardiology, UMCG, Groningen, The Netherlands.

Danielle Robbers-Visser (D)

Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.
Cardiology, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands.

Aeilko H Zwinderman (AH)

Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.
Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands.

Barbara Mulder (B)

Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.
Cardiology, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands.

Aart J Nederveen (AJ)

Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.
Radiology and Nuclear Medicine, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands.

Pim van Ooij (P)

Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.
Radiology and Nuclear Medicine, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands.

Maarten Groenink (M)

Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands.
Cardiology, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands.

Vivian de Waard (V)

Amsterdam Cardiovascular Sciences, Amsterdam, The Netherlands v.dewaard@amsterdamumc.nl.
Medical Biochemistry, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands.

Classifications MeSH