• Published in the European Journal of Preventive Cardiology, the paper demonstrates that polygenic risk score information can be successfully integrated into current general practitioner (GP) clinical practice for the prevention of cardiovascular disease
• The paper also demonstrates that genetic information adds value to GP’s clinical decision-making. In the study, 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
• In addressing efficacy, harm, and logistics, the study passes all three of the criteria suggested by the American Heart Association guiding the implementation of polygenic risk scores (PRSs) in cardiovascular care

OXFORD, England, Jan. 31, 2024 /PRNewswire/ — Genomics plc (Genomics), a healthcare company aiming to transform health through the power of genomics, today announced that the results of its HEART study (Healthcare Evaluation of Absolute Risk Testing) have been published in the European Journal of Preventive Cardiology. The HEART Study is the world’s first clinical trial investigating the use of genomic ‘polygenic risk score (PRS) testing’ to support the prevention of cardiovascular disease (CVD) in National Health Service (NHS) clinical practice. It was designed to evaluate an integrated risk tool (IRT) that combines genetic risk in the form of a polygenic risk score or PRS, with QRISK, a prediction algorithm for CVD.

Genetics is a major risk factor for common diseases, including CVD, but until now, there hasn’t been a 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. The HEART study’s goal was to discover the feasibility of incorporating a tool combining genetic and non-genetic risk factors for CVD into routine primary care while comparing the scores generated by using the integrated tool and the current clinical tool (QRISK©2) to investigate potential changes in treatment plans instigated by the knowledge of the additional risk information provided by genetics. The study found that:

• When Integrated Risk Tool (IRT) scores were calculated, 43 participants (5.2% of the 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 22 (2.6%) 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.
• For people aged 45-64, genetics accounts for 40% as much risk as all the non-genetic risk factors combined in QRISK.
• For men aged 45-54, the effect is even more striking: their polygenic score contributes as much to their overall risk as does the current clinical tool.

Professor Sir Peter Donnelly FRS, FMedSci, Founder and Chief Executive Officer, Genomics plc:

“We are incredibly excited about the publication in the European Journal of Preventive Cardiology and sharing results of this ground-breaking trial. Genetics is a critical risk factor for many of the most common diseases, and the HEART study has shown that its use in the prevention of cardiovascular disease fits well with standard clinical workflows, is very well received by patients, and significantly impacts their clinical management. We hope that it will also encourage similar studies incorporating genetics into clinical risk prediction for other common diseases.”

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 for 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 practices could save lives and be a game-changer for patients and GPs. I am proud to have led such a ground-breaking study.”

METHODOLOGY & RESULTS

The HEART study 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.

HEART enrolled 836 participants across twelve GP practices 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 assessed how useful the clinicians and their patients found it. After every patient interaction, GPs were asked whether the IRT could be straightforwardly incorporated into routine primary care. 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 the follow-up survey, almost all participants reported that they found the test to be personally useful (98.5%) and that the results were easy to understand (94%). Further, 87% of participants said they would recommend the use of this test to friends or family. No study-related or serious adverse effects were reported.

In HEART, in 27.8% of cases in which the participant’s IRT score was greater than their QRISK score, HCPs reported that this change influenced their management decision. When asked, GPs said they would change the management of 108 people (13.1% of the overall study population).

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 that statin use by this group could cut the number of cardiovascular events in this group by 11,000 over 10 years.

There were marked differences between QRISK2 and CVD IRT scores from individual participants. When PRS was added to the QRISK2, 23.9% (199/382) of participants were either re-classified above/below 10% risk, or there was a change in score of over 50%. 

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 uses large-scale genetic information to develop innovative precision healthcare tools, and to bring new understanding to drug discovery. Genomics was founded in 2014 by four world-leading statistical and human geneticists at the University of Oxford. Today, Genomics is collaborating with some of the world’s leading healthcare and drug-discovery organisations and helping them to predict, to prevent, to treat, and to cure – dramatically reducing the human and financial cost of common diseases like cancer, diabetes and heart disease, together with a range of other disease with significant unmet need. The company employs more than 100 people in the UK and the US. For additional information about Genomics plc, please visit www.genomicsplc.com

For additional information about Genomics plc, please visit www.genomicsplc.com; or on LinkedIn or Twitter: @Genomicsplc

Media contact:
BAM on behalf of Genomics plc
[email protected]

SOURCE Genomics plc