靶向血浆多组学提出谷胱甘肽、甘氨酸和丝氨酸作为腹主动脉瘤在连续 CT 扫描中生长的生物标志物。
Targeted plasma multi-omics propose glutathione, glycine and serine as biomarkers for abdominal aortic aneurysm growth on serial CT scanning.
机构信息
Department of Cardiology, Thorax Centre, Cardiovascular Institute, Erasmus MC, Rotterdam, the Netherlands; Department of Vascular Surgery, Erasmus MC, Rotterdam, the Netherlands.
Department of Cardiology, Thorax Centre, Cardiovascular Institute, Erasmus MC, Rotterdam, the Netherlands; Department of Vascular Surgery, Erasmus MC, Rotterdam, the Netherlands; Department of Anesthesiology, Erasmus MC, Rotterdam, the Netherlands.
出版信息
Atherosclerosis. 2024 Nov;398:118620. doi: 10.1016/j.atherosclerosis.2024.118620. Epub 2024 Oct 2.
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.
背景与目的
腹主动脉瘤（AAA）患者接受统一的影像学监测，直到达到手术阈值。尽管对 AAA 病理生理学的持续探索，缺乏个性化监测的生物标志物。本研究旨在确定在连续 CT 扫描中 AAA 生长的潜在循环生物标志物。
方法
本研究纳入了一个多中心前瞻性队列研究中的 AAA（最大直径≥40mm）患者。参与者接受基线采血和每年 CT 成像，以确定 AAA 直径和体积。使用邻近延伸测定法（Olink Cardiovascular III）或单独的 ELISA 试剂盒分别测量蛋白质和代谢物，并使用 LC-TQMS 进行质谱分析。线性混合效应、正交偏最小二乘法和 Cox 回归用于探索生物标志物与 AAA 体积增长率和超越当前指南规定的手术阈值的风险之间的关联。
结果
在 109 名（90.8%为男性）患者中测量了 271 种生物标志物（95 种蛋白质，176 种代谢物），平均年龄为 72 岁。基线时最大 AAA 直径的中位数为 47.8mm，体积为 109ml。平均每年 AAA 体积增长率为 11.5%，95%置信区间（CI）为（10.4，12.7）。中位随访时间为 23.2 个月，49 名患者达到手术阈值。与实际动脉瘤大小相比，基线时谷胱甘肽和甘氨酸水平高出一个标准差的患者，AAA 体积增长率分别为 1.97%，95%CI（0.97，2.97）和 1.74%，95%CI（0.78，2.71）。丝氨酸与达到手术阈值的风险相关，独立于年龄和基线 AAA 大小（每标准差差异的特定原因危险比为 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种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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