The predictive value of molecular and imaging markers for future cardiovascular events and outcomes
Lead Research Organisation:
University of Oxford
Department Name: RDM Radcliffe Department of Medicine
Abstract
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.
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.
People |
ORCID iD |
Christos Kotanidis (Student) |
Publications
Akawi N
(2021)
Fat-Secreted Ceramides Regulate Vascular Redox State and Influence Outcomes in Patients With Cardiovascular Disease.
in Journal of the American College of Cardiology
Akawi N
(2019)
5893Adipose tissue secreted ceramides and related sphingolipids - potential modulators of vascular redox signalling in cardiovascular disease
in European Heart Journal
Akoumianakis I
(2019)
Adipose tissue-derived WNT5A regulates vascular redox signaling in obesity via USP17/RAC1-mediated activation of NADPH oxidases.
in Science translational medicine
Antoniades C
(2019)
State-of-the-art review article. Atherosclerosis affecting fat: What can we learn by imaging perivascular adipose tissue?
in Journal of cardiovascular computed tomography
Antonopoulos A
(2018)
104Metabolically healthy obesity is associated with a distinct epicardial fat phenotype and low myocardial oxidative stress
in European Heart Journal
Evans RA
(2021)
Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study.
in The Lancet. Respiratory medicine
Kondo H
(2019)
P6267Novel direct effects of SGLT2 inhibitor, Canagliflozin, on myocardial redox state in humans
in European Heart Journal
Kondo H
(2021)
Effects of canagliflozin on human myocardial redox signalling: clinical implications
in European Heart Journal
Kondo H
(2020)
Direct effects of canagliflozin on human myocardial redox signalling: a novel role for SGLT1 inhibition
in European Heart Journal
Kotanidis C
(2020)
Epicardial Adipose Tissue - From Cell to Clinic
Kotanidis C
(2020)
Pericoronary fat radiomic profile (FRP) predicts long-term cardiac risk in individuals with calcium score below 100 on coronary computed tomography angiography
in European Heart Journal
Kotanidis C
(2019)
P6282Myocardial redox state predicts 3-year mortality in patients undergoing cardiac surgery: the ox-HVF study
in European Heart Journal
Kotanidis C
(2020)
A novel arterial redox-specific machine learning-derived radiomic signature of perivascular adipose tissue predicts cardiac mortality from routine CCTA
in European Heart Journal
Kotanidis CP
(2018)
Diagnostic Accuracy of Cardiovascular Magnetic Resonance in Acute Myocarditis: A Systematic Review and Meta-Analysis.
in JACC. Cardiovascular imaging
Kotanidis CP
(2022)
Constructing custom-made radiotranscriptomic signatures of vascular inflammation from routine CT angiograms: a prospective outcomes validation study in COVID-19.
in The Lancet. Digital health
Kotanidis CP
(2020)
Selfies in cardiovascular medicine: welcome to a new era of medical diagnostics.
in European heart journal
Kotanidis CP
(2021)
Perivascular fat imaging by computed tomography (CT): a virtual guide.
in British journal of pharmacology
Kotanidis CP
(2022)
Stratifying the risk in chronic coronary syndromes: a ray of hope for ischaemia?
in European journal of preventive cardiology
Kotanidis CP
(2019)
Targeting interleukin-1: implications for long-term cardiovascular management following radiotherapy.
in European heart journal
Nikolaidou C
(2021)
Cardiac Magnetic Resonance to Detect the Underlying Substrate in Patients with Frequent Idiopathic Ventricular Arrhythmias.
in Diagnostics (Basel, Switzerland)
Oikonomou E
(2019)
A novel machine learning-derived radiotranscriptomic signature of perivascular fat improves cardiac risk prediction using coronary CT angiography
in European Heart Journal
Oikonomou E
(2019)
3258Perivascular fat attenuation index stratifies the cardiac risk associated with high-risk plaque features on coronary computed tomography angiography
in European Heart Journal
Oikonomou EK
(2018)
Non-invasive detection of coronary inflammation using computed tomography and prediction of residual cardiovascular risk (the CRISP CT study): a post-hoc analysis of prospective outcome data.
in Lancet (London, England)
Oikonomou EK
(2020)
Perivascular Fat Attenuation Index Stratifies Cardiac Risk Associated With High-Risk Plaques in the CRISP-CT Study.
in Journal of the American College of Cardiology
Tardajos Ayllón B
(2021)
The British Cardiovascular Society Young Investigator Award 2021.
in Heart (British Cardiac Society)
Studentship Projects
Project Reference | Relationship | Related To | Start | End | Student Name |
---|---|---|---|---|---|
EP/N509711/1 | 30/09/2016 | 29/09/2021 | |||
2119518 | Studentship | EP/N509711/1 | 30/09/2018 | 31/12/2021 | Christos Kotanidis |
Title | Oxford Heart, Vessels & Fat Cohort (OX-HVF) |
Description | The Oxford Heart, Vessels & Fat (OX-HVF) cohort consists of a cluster of clinical studies (namely ART Vascular, Bypass Grafts, AdipoRedOx, and ORFAN), which provide synergistic results allowing the deployment of a multi-level strategy to understand the mechanisms of cardiovascular diseases. As each one of the individual studies approaches the issue of cardiovascular disease pathogenesis from a different angle, the OX-HVF cohort provides a unique and powerful platform. The strength of the cohort is the direct access to human tissue (vessels, myocardial and fat biopsies, DNA, plasma and others), in combination with extensive non-invasive cardiovascular phenotyping that includes cardiovascular computed tomography angiography, ultrasound and others. The OX-HVF cohort also collects prospective 10-year clinical outcome data and is linked to the NIHR Bioresource. |
Type Of Material | Database/Collection of data |
Year Produced | 2018 |
Provided To Others? | Yes |
Impact | Multiple. See publications list and website. |
URL | https://oxhvf.com |
Description | ORFAN multicentre study |
Organisation | Cleveland Clinic |
Department | Cleveland Clinic Foundation |
Country | United States |
Sector | Charity/Non Profit |
PI Contribution | Our research team are the coordinators and lead institution for this study, that creates a large prospective registry of individuals who undergo Computed Tomography Imaging of the chest in the UK, with prospective follow up for clinical events. We are the data hub and coordinating centre for any analysis. |
Collaborator Contribution | Patient recruitment, image retrieval, clinical outcome data collection. |
Impact | An Arm of the ORFAN study established by research work created by this UKRI award has been awarded a National Flagship Programme status by the British Heart Foundation/National Institute of Health Research (BHF/NIHR) for the UK C19-CRC project. The project takes advantage of novel artificial intelligence (AI) techniques applied to CT chest scans to accurately measure the level of inflammation in the heart which is suspected to be a cause of severe responses to the SARS-CoV-2 virus. Further information available at the official BHF website: https://www.bhf.org.uk/for-professionals/information-for-researchers/national-flagship-projects |
Start Year | 2018 |
Description | ORFAN multicentre study |
Organisation | Royal United Hospital Bath NHS Trust |
Country | United Kingdom |
Sector | Public |
PI Contribution | Our research team are the coordinators and lead institution for this study, that creates a large prospective registry of individuals who undergo Computed Tomography Imaging of the chest in the UK, with prospective follow up for clinical events. We are the data hub and coordinating centre for any analysis. |
Collaborator Contribution | Patient recruitment, image retrieval, clinical outcome data collection. |
Impact | An Arm of the ORFAN study established by research work created by this UKRI award has been awarded a National Flagship Programme status by the British Heart Foundation/National Institute of Health Research (BHF/NIHR) for the UK C19-CRC project. The project takes advantage of novel artificial intelligence (AI) techniques applied to CT chest scans to accurately measure the level of inflammation in the heart which is suspected to be a cause of severe responses to the SARS-CoV-2 virus. Further information available at the official BHF website: https://www.bhf.org.uk/for-professionals/information-for-researchers/national-flagship-projects |
Start Year | 2018 |
Description | ORFAN multicentre study |
Organisation | University Hospital Erlangen |
Country | Germany |
Sector | Hospitals |
PI Contribution | Our research team are the coordinators and lead institution for this study, that creates a large prospective registry of individuals who undergo Computed Tomography Imaging of the chest in the UK, with prospective follow up for clinical events. We are the data hub and coordinating centre for any analysis. |
Collaborator Contribution | Patient recruitment, image retrieval, clinical outcome data collection. |
Impact | An Arm of the ORFAN study established by research work created by this UKRI award has been awarded a National Flagship Programme status by the British Heart Foundation/National Institute of Health Research (BHF/NIHR) for the UK C19-CRC project. The project takes advantage of novel artificial intelligence (AI) techniques applied to CT chest scans to accurately measure the level of inflammation in the heart which is suspected to be a cause of severe responses to the SARS-CoV-2 virus. Further information available at the official BHF website: https://www.bhf.org.uk/for-professionals/information-for-researchers/national-flagship-projects |
Start Year | 2018 |
Description | ORFAN multicentre study |
Organisation | University of Leicester |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Our research team are the coordinators and lead institution for this study, that creates a large prospective registry of individuals who undergo Computed Tomography Imaging of the chest in the UK, with prospective follow up for clinical events. We are the data hub and coordinating centre for any analysis. |
Collaborator Contribution | Patient recruitment, image retrieval, clinical outcome data collection. |
Impact | An Arm of the ORFAN study established by research work created by this UKRI award has been awarded a National Flagship Programme status by the British Heart Foundation/National Institute of Health Research (BHF/NIHR) for the UK C19-CRC project. The project takes advantage of novel artificial intelligence (AI) techniques applied to CT chest scans to accurately measure the level of inflammation in the heart which is suspected to be a cause of severe responses to the SARS-CoV-2 virus. Further information available at the official BHF website: https://www.bhf.org.uk/for-professionals/information-for-researchers/national-flagship-projects |
Start Year | 2018 |
Description | Patient and Public Involvement Panel for the COVID-19 Flagship programme |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | PPI panel held about COVID-19 research. |
Year(s) Of Engagement Activity | 2020 |