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

IF 5.1 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Heart Pub Date : 2024-09-24 DOI:10.1136/heartjnl-2024-324343
Mitzi Marlotte van Andel, Daan Bosshardt, Eric M Schrauben, Renske Merton, Roland R L van Kimmenade, Arthur Scholte, Michael G Dickinson, Danielle Robbers-Visser, Aeilko H Zwinderman, Barbara Mulder, Aart J Nederveen, Pim van Ooij, Maarten Groenink, Vivian de Waard
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Abstract

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: 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: 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: 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: NL66127.018.18.

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白藜芦醇对马凡综合征患者主动脉生长的影响:单臂开放标签多中心试验。
背景:白藜芦醇是一种干预细胞新陈代谢的膳食补充剂,在马凡氏综合征(MFS)小鼠模型中,白藜芦醇已被证明能降低主动脉生长速度。本研究的主要目的是探讨白藜芦醇对马凡综合征患者主动脉生长速度的影响:在这项由研究者发起的单臂开放标签多中心试验中,我们分析了白藜芦醇治疗 18-50 岁成人 MFS 患者的效果。主要终点是使用线性混合模型评估白藜芦醇治疗一年后胸主动脉五个预定水平的估计年主动脉生长量的变化。在三个时间点通过心脏核磁共振成像测量主动脉直径,以分析开始治疗前后主动脉的年扩张率。此外,还将主动脉的年增长率与之前进行的洛沙坦随机临床试验的增长率进行了比较:36%(61/168)的患者签署了知情同意书,93%(57/61)的患者年龄为 37±9 岁,其中 28 名男性(49%)被纳入研究的最终分析。46%(26/57)的患者在研究前接受过主动脉根部置换术。服用白藜芦醇 1.2±0.3 年后,主动脉根部直径保持稳定。主动脉根部(从0.39±0.06到-0.13±0.23,p=0.072)、升主动脉(从0.40±0.05到-0.01±0.18,p=0.072)和远端降主动脉(从0.32±0.04到0.01±0.14,p=0.072)的估计增长率(毫米/年)呈下降趋势:结论:白藜芦醇治疗一年可稳定成年 MFS 患者的主动脉生长率。结论:白藜芦醇治疗 1 年可稳定 MFS 成年患者的主动脉生长率,但需要后续进行更长随访时间和更大研究群组的随机临床试验,以确定这种膳食补充剂对 MFS 患者的长期实际有益效果:NL66127.018.18.
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来源期刊
Heart
Heart 医学-心血管系统
CiteScore
10.30
自引率
5.30%
发文量
320
审稿时长
3-6 weeks
期刊介绍: Heart is an international peer reviewed journal that keeps cardiologists up to date with important research advances in cardiovascular disease. New scientific developments are highlighted in editorials and put in context with concise review articles. There is one free Editor’s Choice article in each issue, with open access options available to authors for all articles. Education in Heart articles provide a comprehensive, continuously updated, cardiology curriculum.
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