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了解，并可能产生新的心血管事件预测因子。该项目将依赖牛津心脏、血管和脂肪(OxHVF)队列，该队列由一系列研究组成，参与者从接受手术的晚期冠状动脉疾病患者到没有心血管疾病但有风险因素的健康参与者。OxHVF队列的全面生物资源提供了对人体脂肪、动脉、静脉和心肌的活组织检查，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结合来自队列所有方面的数据，以实现其目标。首先，将应用基因组/转录组筛选，以揭示反映氧化应激增加的人类血管壁的新特征。这些信号与公认的氧化还原测量一起，将被测试它们在预测心血管死亡和其他不良事件方面的增量价值，包括但不限于急性心肌梗死、心力衰竭和手术后心房颤动。此外，利用CT成像分析得出的数据，该项目将探索血管和脂肪的成像轮廓在捕捉潜在的分子病理和/或预测疾病发展和进展方面的作用。下一步可以利用牛津大学心血管CT学院的资源来探索和进一步验证候选放射组学标记。该项目有望深入了解氧化应激标记在死亡和主要不良心血管事件中的预测价值，并导致发现用于预测心血管氧化应激和疾病的成像生物标记。

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.