The CVD-COVID-UK project, led by Professor Cathie Sudlow, Director of the BHF Data Science Centre, is one of the seven National Flagship Projects approved by the NIHR-BHF Cardiovascular Partnership.


Background

Cardiovascular disease impact on susceptibility to and poor outcomes from COVID-19

Patients with cardiovascular disease are at increased risk of developing COVID-19 and of poor outcomes of COVID-19, such as admission to hospital or intensive care, or of dying. This could be due to cardiovascular conditions themselves (e.g., heart disease, stroke), their risk factors (e.g., age, raised blood pressure), medications, or combinations of these. Understanding which patients are affected and why will help in developing strategies to reduce this risk.

Impact of infection with coronavirus on patients with cardiovascular disease

The direct impacts include immediate complications (e.g., acute heart injury, stroke) and potentially increased risk of heart attack, stroke and other cardiovascular events in the longer term, through inflammation, blood clotting risk or other factors. However, the nature and extent of these direct effects are not well understood.

Impact of the COVID-19 pandemic on the treatment and care of cardiovascular disease patients

The response by the government and health services to the COVID-19 pandemic also has indirect impacts on the presentation, diagnosis, management and outcomes of cardiovascular diseases. The numbers of people attending hospital with heart attack and stroke declined dramatically in the lead up to and after the announcement of lockdown (as demonstrated by the 4C Initiative). Further, patients were more often arriving too late for beneficial acute treatments (e.g., clot busting drugs) and after potentially preventable complications had developed. To inform government and NHS policy, we urgently need a deeper understanding of these unintended consequences.


Aims

We aim to answer three broad questions (see the protocol for more detail):

  1. What are the effects of cardiovascular diseases, their risk factors and medications on susceptibility to and poor outcomes (including admission to hospital, requirement for intensive care and death) from COVID-19 disease?
  2. What is the direct impact of SARS-CoV-2 infection on acute cardiovascular complications as well as on medium and longer-term cardiovascular risk?
  3. What is the indirect impact of the COVID-19 pandemic and the government and NHS response to it on the presentation, diagnosis, management and outcomes of cardiovascular diseases.

CVD-COVID-UK Consortium Membership, Governance and Project Approvals

An inclusive, open and transparent consortium has been established to work on the CVD-COVID-UK project. Membership comprises data custodians, data scientists with methodological and analytical expertise (statisticians, epidemiologists, health informaticians, bioinformaticians, computer scientists and others) and clinicians (including cardiologists, stroke physicians, vascular surgeons and others), all of whom have signed up to an agreed set of principles.

To become a member of the consortium, please e-mail: bhfdsc@hdruk.ac.uk. You will be sent a copy of the principles document that you must agree to before becoming a member of the consortium.

The Approvals and Oversight Board of CVD-COVID-UK consists of representatives from data custodians, data controllers, researchers and lay members, coordinated by the operations team of the BHF Data Science Centre and chaired by the BHF Data Science Centre Director. Signed-up consortium members have access to project proposal forms to submit to the Approvals and Oversight Board for review. Project proposals must be within scope of the ethical and regulatory approvals of the CVD-COVID-UK programme of work, which covers the relationship between cardiovascular disease and COVID-19.

For any queries regarding governance, membership or project submissions, please e-mail: bhfdsc@hdruk.ac.uk


Datasets

Researchers will access routinely collected datasets across the whole population of the UK within secure trusted research environments provided by NHS Digital in England, the National Data Safe Haven in Scotland, the SAIL Databank in Wales and the Honest Broker Service in Northern Ireland.

The current CVD-COVID-UK TRE dataset provisioning dashboard can be viewed here.

Details about the datasets in the TRE can be found in the Health Data Research Innovation Gateway.


Projects

The following projects have been formally approved by the CVD-COVID-UK Approvals & Oversight Board:

Data Management and Analysis methods (Lead: Angela Wood, University of Cambridge)

Since the COVID-19 pandemic, there has been rapid progress made towards the availability and accessibility of national healthcare data for research. Consequently, for the first time we are analysing data from over 65 million patients across the UK to help us understand more about COVID-19. Our analyses have the advantages of being able to study individuals with and without different health-related problems across all age groups, ethnicities, geographies and socioeconomic settings. Our results will be directly relevant to everyone living in the UK.

However, there are a number of challenges and limitations to using routinely collected healthcare data for research. The problems mainly arise because electronic health records are designed for clinical purposes, and do not necessary provide an accurate picture of the true health status on all patients at all times. If we do not address these problems properly in the analysis, then we will get biased results and make incorrect conclusions.

We aim to identify and provide solutions to address the challenges and limitations in the analysis of population-wide healthcare data. Ultimately, we want to ensure results arising from population-data healthcare data are accurately reported.

BMJ publication 08/04/21 can be viewed here.

BMJ editorial 08/04/21 can be viewed here and public contributor opinion piece here.

MedRxiv pre-print 26/02/21 can be viewed here.

Code is now also available on the Github repository which can be found here.


Investigating the effects of angiotensin converting enzyme inhibitors and angiotensin receptor blockers on COVID-19 outcomes (Lead: Jonathan Sterne, University of Bristol)

ACE inhibitors and angiotensin receptor blockers are drugs that are commonly used to lower high blood pressure. These drugs may affect the ability of the coronavirus to enter cells of the body and cause COVID-19. We plan to investigate whether use of these drugs affects people’s chance of becoming infected or unwell with COVID-19.

We will conduct carefully planned analyses of data from millions of people’s healthcare records. These records provide information about people’s health and prescribed medications, as well as on which people became infected or unwell with COVID-19.

People who take drugs to lower their blood pressure are more likely to have other risk factors for becoming infected or unwell with COVID-19. Our analysis methods will account for these risk factors, to work out whether any change in risk is due to the blood pressure lowering drugs themselves.

Our results will help to inform the way that blood pressure lowering drugs are used in the future, particularly while the pandemic continues.


SARS-CoV-2 infection and risk of venous thromboembolism and arterial thrombotic events (Lead: William Whiteley, University of Edinburgh)

Coronavirus infection (‘COVID-19’) might increase a person’s chance of having a stroke, heart attack or clot in the deep veins or lungs (‘blood vessel diseases’).

During the COVID-19 pandemic, some doctors have looked after patients with COVID-19 who also had unusual strokes, clots or heart complaints. This suggests there could be a link between COVID-19 and blood vessel diseases. But no individual doctor will see enough patients to find out if COVID-19 really does increase the risk of blood vessel diseases.

To understand more, we will use healthcare records to study every person alive in England, Scotland and Wales at the beginning of the pandemic in 2020. We will find out how many people had a stroke, heart attack, heart condition or other disease of the blood vessels over the following year.

We will compare the number of people with COVID-19 infection who developed a blood vessel disease with the number of people without COVID-19 infection who developed a blood vessel disease. Different types of people might have different risks, so we will also examine people of different ages, ethnicities and medical history.

The result of this research will be an estimate of how much COVID-19 increases the risk of different blood vessel diseases. This information is needed so that people with COVID-19 know whether they need to worry about blood vessel diseases as they recover. If this research shows there is an increased risk, then treatments might be needed to reduce this.

Amendment to approved project made on 8th April 2021:

There have been a number of reports of vascular complications after coronavirus vaccination. The complication that is of most concern is a very rare condition of clotting of the veins in unusual places like the brain and the gut which has been associated with low levels of platelets.

As an extension to the project outlined above, we will find out which people in England had a disease involving blood clots in the arteries or veins, and also diagnosed with low platelet levels. We will compare the risk of developing one of these conditions among people who have had a COVID-19 vaccine versus those who have not had a vaccine. We will assess the risks for clotting events of different types, for different vaccines, for people who have had one or two vaccine doses, and for people with different characteristics. Our results will allow us to estimate whether COVID-19 vaccine is associated with an increased risk of one or more of these different types of clotting events, and if so by how much.

This research is needed to provide reliable information to medicines regulators, the Department of Health and Social Care, health professionals and the public about any risks associated with COVID-19 vaccines. Because the clotting events that might be affected are very rare, any increase in risk is likely to be very small. It will, therefore, be important to understand not only whether or not there is an increased risk but also the size of any increased risk and whether it only applies to particular groups of people. It will also be important to understand how any risk compares with the protective benefits of the vaccine, which are known to be substantial.


Direct and indirect effects of the coronavirus (COVID-19) pandemic in individuals with cardiovascular disease (Lead: Ami Banerjee, University College London)

Coronavirus (COVID-19) directly impacts individuals who become infected with the virus. It can also influence people’s healthcare decisions (such as deciding not to attend medical appointments for fear of infection). In addition, hospitals have sometimes had to prioritise treatment of COVID-19 patients over routine healthcare.

Access to data from healthcare records will help to improve our understanding of what puts certain people at an increased level of risk. This includes people with cardiovascular disease, including heart disease and stroke.

This research project has three main priorities.

  1. For people with cardiovascular disease, we will estimate by how much becoming infected or unwell with COVID-19 increases their risk of dying within one year of infection. This will involve analysing routine healthcare data from multiple sources, including from general practices, hospitals and national death registers.
  2. We will study how the treatment of patients with cardiovascular disease has been affected during the pandemic.
  3. We will develop and improve models that predict the risk of dying at one year among people with cardiovascular disease who have and who have not contracted COVID-19.

Our research will help to shape health policy, help patients and clinicians to make more informed decisions, and improve health outcomes.


COVID and Cardiovascular Disease Risk Prediction (Lead: Angela Wood, University of Cambridge)

Cardiovascular disease (CVD), comprising mostly heart attacks and strokes, is one of the UK’s leading causes of death and disability. It is far better and cheaper to prevent CVD than to treat patients after they get sick. Consequently, doctors aim to identify patients at high risk of future CVD and offer healthy lifestyle advice and medication, such as statins.

However, studies have found that such advice is poorly communicated to patients. This has resulted in low numbers of patients choosing to make healthy lifestyle changes and take medication, especially amongst patients living in more deprived areas. It is important to improve the way CVD risk is communicated to patients across the whole of society so that more people benefit from advice and medication, and also to reduce inequalities in CVD.

Currently, doctors use risk prediction calculators to help decide whether a patient is at high risk of future CVD. The most commonly used risk prediction calculators in England were developed using data from 2004-2016 from 2.3 million patients in England. More current data is now available from over 56 million patients in England, as well as 10 million patients from Wales, Scotland and Northern Ireland. These datasets also include information about whether a patient has had COVID-19 and any related complications. Patients with COVID-19 complications may be at higher risk of future CVD than patients without COVID-19 complications. Therefore, COVID-19 information may be useful information for doctors in helping to identify the right patients at high risk of CVD.

We plan to develop new risk prediction tools to assess and help communicate a patients’ future risk of CVD. Our aims are (i) to better identify patients at high risk of CVD in the UK and (ii) to improve communication of CVD risk to patients across the whole of society. Ultimately, this should reduce CVD in the UK.


High-throughput electronic health record phenotyping approaches (Lead: Spiros Denaxas, University College London)

When a patient visits their GP or is admitted into hospital, information about their symptoms, diagnosis, lab test results and prescriptions is inputted and stored in ‘Electronic Health Records’ (‘EHRs’). These EHR’s are a valuable resource for researchers and clinicians to be able to analyse the health data of large numbers of patients, with the aim of using this information to improve patient health and care.

However, as information in these EHRs is inputted by different health workers around the UK, there can be variations in the amount of detail that has been included and the records can contain many inconsistencies. This means that researchers need to initially spend a considerable amount of time and effort to be able to obtain the most relevant information from these EHRs, before they can then start to effectively analyse them. Examples include trying to identify which patients may or may not have a particular disease, or to extract individual measurements – such as high blood pressure or whether they are a smoker – from billions of rows of data.

To improve this, this project will create and evaluate different ways of being able to extract this valuable information from complex EHRs, so that the records can be most effectively analysed by the CVD-COVID-UK consortium. As our understanding of COVID-19 is developing rapidly, being able to access accurate information for research more quickly is especially important. This includes being able to accurately understand the impact that COVID-19 infection has in patients in the longer term – known as ‘long COVID’ – which affects multiple organs in the body.

The approaches developed in this project will benefit all of the research being undertaken by the CVD-COVID-UK consortium, and shared with the wider scientific and medical community by publishing the results openly. This will maximise the benefits of using information from EHRs, and ensure research can be reproduced effectively. Most importantly, this will speed up the ability to effectively analyse health information in EHRs, and directly improve benefits to patients and healthcare.


Assessing cardiovascular disease impact through medicines (Lead: Reecha Sofat, University College London)

Cardiovascular disease (CVD, including heart attacks and strokes) remains one of the leading causes of death in the UK. There are a number of conditions that commonly increase an individual’s risk of developing CVD. Some of these conditions, such as diabetes and having high circulating levels of cholesterol in the blood, can be controlled by using medicines.

However, these conditions need to be diagnosed before an individual can be prescribed the medicines to control them. Because of disruption from the COVID-19 pandemic resulting in changes in health care services and fewer face-to-face medical appointments, it is likely that the number of conditions being diagnosed has fallen. Therefore some individuals are not being prescribed the medicines to control the condition.

One way to investigate this problem is to look at what changes there have been in the prescriptions for these conditions. This involves looking at new and repeat prescriptions that have been issued by the GP, and also the amount of prescriptions dispensed by the pharmacy.

We already know that the COVID-19 pandemic caused a disruption to the usual pattern of prescribing of medicines for these conditions. For example, there was a significant increase in the number of repeat prescriptions issued in March 2020, presumably as doctors and patients ensured they had sufficient medication for the first lockdown. Subsequent patterns in the prescribing of medicines for these conditions during 2020 have not yet been adequately studied.

The number of GP appointments also fell during Spring-Summer 2020, presumably resulting in a reduced number of individuals being diagnosed with CVD. It is also presumed that there would be a reduction in the diagnosis in new patients of conditions that can increase their risk of developing CVD, and therefore a decrease in the amount of prescriptions for medicines to control these conditions.

For this project, we therefore propose to examine patterns in the prescription of medicines for these conditions. This will enable us to understand how the COVID-19 pandemic has had an impact on the control of CVD and its related conditions in the UK population. We will use this information to understand how many people are likely to be affected by cardiovascular disease in the future. It is hoped that this will enable more accurate planning for better patient care.


Impact of COVID-19 pandemic on Congenital Heart Disease (CHD) patients undergoing cardiac surgery (Lead: Massimo Caputo, University of Bristol)

13 babies in the UK are born with congenital heart disease (CHD) every day, and most of these children will need several high-risk operations and treatments during their lives. There is currently very limited information available regarding how delays to treatment caused by the COVID-19 pandemic has affected children and young adults with CHD undergoing these very high-risk interventions.

We will be using healthcare records from England, Wales and Scotland to better understand  the risks between delaying surgery because of the pandemic or not, and if so what length of delay remains safe for children with CHD. We will also evaluate whether the COVID-19 pandemic has affected the future health and wellbeing of these children and young adults with CHD. This will include seeing if there is impact on their schooling and education, and whether there are any differences in the impact of the pandemic on young patients with CHD based on race and ethnicity.

The information obtained from this research will allow for better planning of operations and treatments, aiming to improve health outcomes for children and young adults with CHD. The findings of this project will help patients and clinicians to make more informed decisions during these challenging pandemic times.


Patient and Public Involvement and Engagement

The CVD-COVID-UK Approvals and Oversight Board includes four lay members who ensure the lay/patient voice is considered and embedded appropriately in this work. As part of the Board, the lay members review and discuss project proposals with researchers to ensure work being carried out meets the interests of people affected by heart and circulatory disease, address any patient and/or public concerns, and advise on best approaches to patient and public involvement in the projects.


Privacy Statement and Acknowledgements

The CVD-COVID-UK programme privacy statement explains how the partners involved in the CVD-COVID-UK consortium collect, store, manage and protect your personal data. It outlines the types of data that are accessed and how we use them.

To appropriately acknowledge our funders and recognise the use of patient data in our research outputs and publications, please use one of the following acknowledgements:

This work was funded by the BHF as part of the BHF Data Science Centre led by HDR UK (BHF Grant no. SP/19/3/34678). This work uses data provided by patients and collected by the NHS as part of their care and support. We would also like to acknowledge all data providers who make anonymised data available for research.

or

This work is carried out with the support of the BHF Data Science Centre led by HDR UK (BHF Grant no. SP/19/3/34678). This work uses data provided by patients and collected by the NHS as part of their care and support. We would also like to acknowledge all data providers who make anonymised data available for research.


News and events

The BHF Data Science Centre hold a monthly webinar that provides a brief update on the work in the centre followed by one or two short presentations on emerging research outputs (focussing initially on CVD-COVID-UK).

The recordings of these webinars can be found on the BHF Data Science Centre YouTube channel

Find out more about the BHF Data Science Centre