Plasma Protein Profiling of Incident Cardiovascular Diseases: A Multisample Evaluation.

IF 6 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Circulation: Genomic and Precision Medicine Pub Date : 2023-12-01 Epub Date: 2023-11-28 DOI:10.1161/CIRCGEN.123.004233
Lars Lind, Olga Titova, Rui Zeng, Daniela Zanetti, Martin Ingelsson, Stefan Gustafsson, Johan Sundström, Johan Ärnlöv, Sölve Elmståhl, Themistocles Assimes, Karl Michaëlsson
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Abstract

Background: Proteomic profiling could potentially disclose new pathophysiological pathways for cardiovascular diseases (CVD) and improve prediction at the individual level. We therefore aimed to study the plasma protein profile associated with the incidence of different CVDs.

Methods: Plasma levels of 245 proteins suspected to be linked to CVD or metabolism were measured in 4 Swedish prospective population-based cohorts (SIMPLER [Swedish Infrastructure for Medical Population-Based Life-Course and Environmental Research], ULSAM (Uppsala Longitudinal Study of Adult Men), EpiHealth, and POEM [Prospective Investigation of Obesity, Energy Production, and Metabolism]) comprising 11 869 individuals, free of CVD diagnoses at baseline. Our primary CVD outcome was defined by a combined end point that included either incident myocardial infarction, stroke, or heart failure.

Results: Using a discovery/validation approach, 42 proteins were associated with our primary composite end point occurring in 1163 subjects. In separate meta-analyses for each of the 3 CVD outcomes, 49 proteins were related to myocardial infarction, 34 to ischemic stroke, and 109 to heart failure. Thirteen proteins were related to all 3 outcomes. Of those, urokinase plasminogen activator surface receptor, adrenomedullin, and KIM-1 (kidney injury molecule 1) were also related to several markers of subclinical CVD in Prospective Investigation of Obesity, Energy production and Metabolism, reflecting myocardial or arterial pathologies. In prediction analysis, a lasso selection of 11 proteins in ULSAM improved the discrimination of CVD by 3.3% (P<0.0001) in SIMPLER when added to traditional risk factors.

Conclusions: Protein profiling in multiple samples disclosed several new proteins to be associated with subsequent myocardial infarction, stroke, and heart failure, suggesting common pathophysiological pathways for these diseases. KIM-1, urokinase plasminogen activator surface receptor, and adrenomedullin were novel early markers of CVD. A selection of 11 proteins improved the discrimination of CVD.

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血浆蛋白谱分析事件心血管疾病:多样本评估。
背景:蛋白质组学分析可以潜在地揭示心血管疾病(CVD)的新的病理生理途径,并提高个体水平的预测。因此,我们旨在研究血浆蛋白谱与不同心血管疾病发病率的关系。方法:在4个瑞典前瞻性人群队列(simple[瑞典基于医疗人群的生命过程和环境研究基础设施]、ULSAM(乌普萨拉成年男性纵向研究)、EpiHealth和POEM[肥胖、能量产生和代谢的前瞻性调查])中测量了245种疑似与CVD或代谢相关的血浆蛋白水平,这些队列包括11869名基线无CVD诊断的个体。我们的主要CVD结局是由合并终点定义的,包括心肌梗死、中风或心力衰竭。结果:采用发现/验证方法,在1163名受试者中发现42种蛋白质与我们的主要复合终点相关。在对3种CVD结果的单独荟萃分析中,49种蛋白质与心肌梗死相关,34种与缺血性卒中相关,109种与心力衰竭相关。13种蛋白与所有3种结果相关。其中,尿激酶纤溶酶原激活物表面受体、肾上腺髓质素和KIM-1(肾损伤分子1)在肥胖、能量产生和代谢的前瞻性研究中也与亚临床CVD的几个标志物相关,反映心肌或动脉病变。在预测分析中,对ULSAM中11种蛋白的筛选使CVD的鉴别率提高了3.3%(结论:多个样品的蛋白分析揭示了与随后的心肌梗死、中风和心力衰竭相关的一些新蛋白,提示了这些疾病的共同病理生理途径。KIM-1、尿激酶纤溶酶原激活物表面受体和肾上腺髓质素是CVD新的早期标志物。11个蛋白的选择提高了CVD的识别。
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来源期刊
Circulation: Genomic and Precision Medicine
Circulation: Genomic and Precision Medicine Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
9.20
自引率
5.40%
发文量
144
期刊介绍: Circulation: Genomic and Precision Medicine is a distinguished journal dedicated to advancing the frontiers of cardiovascular genomics and precision medicine. It publishes a diverse array of original research articles that delve into the genetic and molecular underpinnings of cardiovascular diseases. The journal's scope is broad, encompassing studies from human subjects to laboratory models, and from in vitro experiments to computational simulations. Circulation: Genomic and Precision Medicine is committed to publishing studies that have direct relevance to human cardiovascular biology and disease, with the ultimate goal of improving patient care and outcomes. The journal serves as a platform for researchers to share their groundbreaking work, fostering collaboration and innovation in the field of cardiovascular genomics and precision medicine.
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