The predictive value of molecular and imaging markers for future cardiovascular events and outcomes

该项目的目的是研究人类血管和脂肪的分子和成像表型，以促进对心血管疾病易感性的理解，并可能产生新的心血管事件预测因子。该项目将依赖于牛津心脏、血管和脂肪（OxHVF）队列，该队列由一组研究组成，包括从接受手术的晚期冠状动脉疾病患者到有风险因素但无心血管疾病的健康参与者。OxHVF队列的综合生物资源提供了对人体脂肪、动脉、静脉和心肌活检的访问，以及丰富的心血管成像数据库，主要使用计算机断层扫描（CT）成像。该项目将试图利用和联合收割机从队列的各个方面收集的数据，以实现其目标。首先，将应用基因组/转录组学筛选，以揭示反映氧化应激增加的人类血管壁的新特征。然后将测试这些特征以及完善的氧化还原测量结果在预测心血管死亡和其他不良事件（包括但不限于急性心肌梗死、心力衰竭和术后房颤）中的增量值。此外，利用来自CT成像分析的数据，该项目将探索血管和脂肪的成像特征在捕获潜在分子病理学和/或预测疾病发展和进展中的作用。候选放射组学标记物可以下一步探索和进一步验证使用牛津大学学术心血管CT Unit.This项目的资源，预计将深入了解氧化应激标记物在死亡和主要不良心血管事件的预测价值，以及导致发现用于预测心血管氧化应激和疾病的成像生物标志物。

The aim of this project is to investigate the molecular and imaging phenotype of the human vessels and fat, in order to advance understanding of the predisposition to cardiovascular disease and to possibly produce novel predictors of cardiovascular events. The project will rely on the Oxford Heart, Vessels and Fat (OxHVF) cohort, which consists of a cluster of studies including participants ranging from patients with advanced coronary artery disease undergoing surgery to healthy participants with risk factors but no cardiovascular disease. The comprehensive bio resource of the OxHVF cohort supplies access to biopsies of human fat, arteries, veins and myocardium, as well as to a rich cardiovascular imaging database, mainly using computed tomography (CT) imaging. The project will attempt to exploit and combine data from all aspects of the cohort, towards its aim. At first, a genomic/transcriptomic screening will be applied so as to unveil novel signatures of the human vascular wall that reflect increased oxidative stress. These signatures alongside well-established redox measurements will then be tested for their incremental value in predicting cardiovascular death and other adverse events, including but not limited to, acute myocardial infarction, heart failure, and post-operative atrial fibrillation. In addition, using data derived from CT imaging analyses, the project will explore the role of the imaging profile of the vessels and fat in capturing underlying molecular pathology and/or predicting disease development and progression. Candidate radiomic markers can be next explored and further validated using resources of the Oxford Academic Cardiovascular CT Unit.This project is expected to give insight into the predictive value of markers of oxidative stress in death and major adverse cardiovascular events, as well as lead to the discovery of imaging biomarkers for predicting cardiovascular oxidative stress and disease.