Published 7 Nov 2022

Successful world-first pilot using improved genomic risk assessment in cardiovascular disease prevention carried out in the NHS

The HEART study is the world’s first to demonstrate successful integration of polygenic risk scores into current GP clinical practice for the prevention of cardiovascular disease

Further results show 24% of participants had clinically significant changes in their CVD risk when genetic information was added to QRISK in an integrated risk tool

GPs reported they would change their management of 108 people or 13.1% of the overall study population as a result of knowing their integrated risk

From the American Heart Association Annual Scientific Sessions, Chicago – The world’s first pilot investigating the use of genomic ‘polygenic risk score (PRS) testing’ to support the prevention of cardiovascular disease (CVD) in NHS clinical practice, has reported significant, positive results at the American Heart Association Scientific Sessions today.

The HEART study (Healthcare Evaluation of Absolute Risk Testing) investigated using genetic information to augment the current best practice risk assessment and clinical decision tool used by NHS GPs to help prevent and manage CVD (QRISK©2). QRISK incorporates factors such as blood pressure, cholesterol, BMI, smoking status, age, sex, and family history to estimate risk. It is an essential tool for GPs to identify patients at high risk of CVD, and to guide management and treatment decisions, for example, lifestyle changes or starting a patient on statins. Individuals receive a percentage score indicating their chances of having a heart attack or stroke over the next 10 years. A score above 10% indicates they are at high risk.

Genetics is also a major risk factor for all the common diseases, including CVD. Until now there has been no way of measuring a person’s overall genetic risk for most diseases, meaning that there are many people at high risk who have been invisible to the NHS. For people aged 45-64, genetics accounts for 40% as much risk as all the non-genetic risk factors combined in QRISK. HEART was designed to evaluate an integrated risk tool (IRT) which combined this genetic risk in the form of a polygenic risk score or PRS, with QRISK.

HEART set out to check whether incorporating genetic testing into current best practice was straightforward, without increasing the burden on practice staff at a time of stretched resources and high workloads. It also assessed the effect of adding genetic information to QRISK, looking at the changes in risk that resulted, and the impact of these on the clinical management decisions made by GPs. In the trial no individuals were denied treatment they would have received under standard of care.

HEART ran across twelve local GP practices in the North-East and North Cumbria, led by Professor Ahmet Fuat, a Darlington GP specialising in cardiology, and NECS (North of England Care System Support), in partnership with the NIHR Clinical Research Network, and Genomics plc, the company which developed the IRT and leads the world in the development of PRS-powered tools.

HEART enrolled 836 participants aged between 45 and 64 who were invited for their NHS Health Check and offered additional PRS IRT testing. Of these 824 completed the study including follow-up.

The pilot met its primary outcome – whether it was practical for GPs to use the new tool, and how useful they and their patients found it. After every patient interaction, GPs were asked whether the IRT could be incorporated into routine primary care in a straightforward manner. At the end of the study, more than 90% (90.7%; 747/824) of the GP responses agreed that it could be.

Similarly, 87% of participants responding to a study survey said they would recommend the use of this test to friends or family, with almost all saying they found the test to be personally useful (98.5%) and that the results were easy to understand (94%). No study-related or serious adverse effects were reported.

In HEART, 24% of participants saw changes to their risk score that were clinically significant when the IRT was used (having their risk level reclassified or having a change in risk of 50% or more). When asked, GPs said they would change the management of 108 people (13.1% of the overall study population).

In England and Wales, an individual with a CVD risk score of more than 10% is classified as being at high risk. When IRT scores were calculated, 43 participants (5.2% of study population) who had been classified as low risk were found to be at high risk (moving from QRISK below 10%, to a risk of more than 10% with the IRT). A further 23 (2.8%) participants moved from being at high risk (QRISK score more than 10% and below 20%) to very high risk (20% or more), when the IRT was used.

Previous modelling by Genomics has suggested that if the test were used across England among all individuals aged 45 to 64 it would identify 700,000 extra people whose risk of CVD would be high enough to be recommended statin treatment and could cut the number of cardiovascular events in this group by 11,000 over 10 years.

Professor Ahmet Fuat, Chief Investigator HEART, GPwSI in Cardiology, and Honorary Professor of Primary Care Cardiology at Durham University:
“The HEART study has shown us that this kind of genomic testing has the potential to transform the way we manage cardiovascular disease in primary care. Prevention is at the heart of what we do as GPs and risk assessment underpins that. We have shown in HEART that genomic testing improves how we identify those patients who most need preventative measures, closer management, and treatment, and helps us target the right interventions to them. I changed my management of a number of my patients directly due to the new information coming through from the integrated tool. Some patients who had been reluctant to start statin therapy, for example, became keen to take them when the new risk scores came through. We could not show it in a short study like this, but I believe this approach of integrating genetic information into routine best practice could save lives and be a game-changer for patients and GPs. I am proud to have led such a ground-breaking study.”

Professor Sir Peter Donnelly FRS, FMedSci, Founder and Chief Executive Officer, Genomics plc:
“Genetics is a critical risk factor for many of the most common diseases. That means we can use it to improve health outcomes for patients and ease the pressure placed on doctors and the resources of health systems like the NHS. At Genomics we are focused on developing techniques and tools to do just that and the results from HEART clearly demonstrate the effectiveness of this approach in practice. Our PRS-powered tool clearly helped participants and their GPs to make better decisions about how to manage and prevent cardiovascular disease. We hope that this is an important first step towards a more widespread uptake and adoption of genomic approaches like this. HEART studied the impact in CVD, but in future a single blood sample could be used to calculate an individual’s risk of many different common diseases simultaneously, and earlier than current methods allow, allowing prevention and treatment more time to work.”

Stephen Childs, Managing Director, NHS North of England Care System Support (NECS):
“Understanding how we can better assess a patient’s risk of disease has been a longstanding commitment of NECS. For over 10 years, we have been working with GPs to develop algorithms that we apply to primary data through our digital application, RAIDR. Around 900 practices across the North East and North Cumbria, Yorkshire and Humber and Derbyshire are using RAIDR on a daily basis to enhance the care of their patients by supporting data driven decision making. We continuously seek to augment the benefits to patients through the effective use of data. Our long-term goal is to support clinicians to cost-effectively harness the identification of phenotype and genotype factors to facilitate more targeted care
and interventions. We have been honoured to make a contribution to this study and delighted that it is generating such useful insight.”


About PRS
Genetics is an important risk factor for many common diseases like CVD, and others including diabetes, osteoporosis, and common cancers like breast, prostate, and bowel cancer. Small differences in our DNA in millions of positions, although insignificant on their own, can add up to affect our risk of developing a disease. This can be captured in a polygenic risk score, which can be used to improve risk assessment and prediction, particularly when combined with existing methods. Risk assessment is essential to identify the patients who would benefit from preventative measures, such as lifestyle changes, extra screening, or treatments, for example, statins to lower cholesterol. Identifying patients and getting them onto the right
measures will help the NHS to improve outcomes and use resources more efficiently.

About Genomics plc
Genomics plc is a pioneering healthcare company that aims to transform health through the power of genomics. In 2014, Peter Donnelly and three colleagues founded Genomics plc, spinning it out of the University of Oxford, with Peter becoming CEO in 2017. The company, which now employs over 100 people in the UK and the US, uses an extensive data platform and novel analytical tools in two areas: to understand disease biology and find new drug targets; and to enable a prevention-first approach to healthcare by using its powerful risk prediction tools to get more of the right people into the appropriate screening, diagnosis, and treatment pathways.

About NECS
NECS, North of England Care System Support, provides services to strategic partners across the health and social care system with the aim of improving population health, enhancing patient experience and reducing cost. Current customers include Integrated Care Boards and Integrated Care Systems (ICS), NHS providers, NHS England and Local Authorities. NECS has a unique Customer-Ownership model where
representatives of our largest customer organisations (ICBs, Provider Collaboratives and NHS England) sit on our Customer Board. Over the last nine years, NECS has re-invested £30m into innovative initiatives including prevention schemes and the appointment of Public Health consultants to improve outcomes for local communities. NECS employs more than 1800 people, many with specialist knowledge and skills and has a turnover of in excess of £100m per annum.