Targeted plasma multi-omics propose glutathione, glycine and serine as biomarkers for abdominal aortic aneurysm growth on serial CT scanning

IF 4.9 2区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Atherosclerosis Pub Date : 2024-10-02 DOI:10.1016/j.atherosclerosis.2024.118620

Alexander Vanmaele , Elke Bouwens , Sanne E. Hoeks , Alida Kindt , Lieke Lamont , Bram Fioole , Ricardo PJ. Budde , Sander ten Raa , Burhan Hussain , José Oliveira-Pinto , Arne S. Ijpma , Felix van Lier , K. Martijn Akkerhuis , Danielle F. Majoor-Krakauer , Jorg L. de Bruin , Thomas Hankemeier , Yolanda de Rijke , Hence JM. Verhagen , Eric Boersma , Isabella Kardys

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Abstract

Background and aims

Abdominal aortic aneurysm (AAA) patients undergo uniform imaging surveillance until reaching the surgical threshold. In spite of the ongoing exploration of AAA pathophysiology, biomarkers for personalized surveillance are lacking. This study aims to identify potential circulating biomarkers for AAA growth on serial CT scans.

Methods

Patients with an AAA (maximal diameter ≥40 mm) were included in this multicentre, prospective cohort study. Participants underwent baseline blood sampling and yearly CT-imaging to determine AAA diameter and volume. Proteins and metabolites were measured using proximity extension assay (Olink Cardiovascular III) or separate ELISA panels, and mass-spectrometry (LC-TQMS), respectively. Linear mixed-effects, orthogonal partial least squares, and Cox regression were used to explore biomarker associations with AAA volume growth rate and the risk of surpassing the surgical threshold, as formulated by current guidelines.

Results

271 biomarkers (95 proteins, 176 metabolites) were measured in 109 (90.8 % male) patients with mean age 72. Median baseline maximal AAA diameter was 47.8 mm, volume 109 mL. Mean annual AAA volume growth rate was 11.5 %, 95 % confidence interval (CI) (10.4, 12.7). Median follow-up time was 23.2 months, 49 patients reached the surgical threshold. Patients with one standard deviation (SD) higher glutathione and glycine levels at baseline had an AAA volume growth rate that respectively was 1.97 %, 95%CI (0.97, 2.97) and 1.74 %, 95%CI (0.78, 2.71) larger, relative to the actual aneurysm size. Serine was associated with the risk of reaching the surgical threshold, independent of age and baseline AAA size (cause-specific hazard ratio per SD difference 1.78, 95%CI (1.30, 2.44)).

Conclusions

Among multiple intertwined biomarkers related to AAA pathophysiology and progression, glutathione, glycine and serine were most promising.

Abstract Image

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靶向血浆多组学提出谷胱甘肽、甘氨酸和丝氨酸是连续 CT 扫描显示腹主动脉瘤生长的生物标记物。

背景和目的：腹主动脉瘤（AAA）患者在达到手术临界值之前都要接受统一的成像监测。尽管人们一直在探索 AAA 的病理生理学，但仍缺乏用于个性化监测的生物标志物。本研究旨在通过连续 CT 扫描确定 AAA 生长的潜在循环生物标志物：这项多中心前瞻性队列研究纳入了 AAA 患者（最大直径≥40 毫米）。参与者接受基线血液采样和每年一次的 CT 扫描，以确定 AAA 的直径和体积。蛋白质和代谢物分别采用近距离延伸测定法（Olink Cardiovascular III）或单独的酶联免疫吸附测定法（ELISA）和质谱分析法（LC-TQMS）进行测定。采用线性混合效应、正交偏最小二乘法和 Cox 回归来探讨生物标记物与 AAA 体积增长率和超过现行指南规定的手术阈值风险之间的关系。结果：在平均年龄为 72 岁的 109 名患者（90.8% 为男性）中测量了 271 种生物标记物（95 种蛋白质、176 种代谢物）。AAA 最大基线直径中位数为 47.8 毫米，体积为 109 毫升。AAA 体积年平均增长率为 11.5%，95% 置信区间 (CI) (10.4, 12.7)。中位随访时间为 23.2 个月，49 名患者达到了手术阈值。基线时谷胱甘肽和甘氨酸水平高出一个标准差（SD）的患者，其 AAA 体积增长率相对于实际动脉瘤大小分别大 1.97%，95% 置信区间（0.97，2.97）和 1.74%，95% 置信区间（0.78，2.71）。丝氨酸与达到手术阈值的风险相关，与年龄和基线 AAA 大小无关（每 SD 差异的特异性危险比为 1.78，95%CI (1.30，2.44)）：结论：在与 AAA 病理生理学和进展相关的多个相互交织的生物标志物中，谷胱甘肽、甘氨酸和丝氨酸最有希望。

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来源期刊

Atherosclerosis 医学-外周血管病

CiteScore

9.80

自引率

3.80%

发文量

1269

审稿时长

36 days

期刊介绍： Atherosclerosis has an open access mirror journal Atherosclerosis: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. Atherosclerosis brings together, from all sources, papers concerned with investigation on atherosclerosis, its risk factors and clinical manifestations. Atherosclerosis covers basic and translational, clinical and population research approaches to arterial and vascular biology and disease, as well as their risk factors including: disturbances of lipid and lipoprotein metabolism, diabetes and hypertension, thrombosis, and inflammation. The Editors are interested in original or review papers dealing with the pathogenesis, environmental, genetic and epigenetic basis, diagnosis or treatment of atherosclerosis and related diseases as well as their risk factors.