AHA 2025: New study from Genomics shows polygenic risk scores improve the accuracy of cardiovascular disease risk prediction

• The addition of polygenic risk scores (PRS) improved the accuracy of the cardiovascular disease (CVD) risk prediction tool PREVENT across all groups studied, across ancestries.
• Over 3 million people aged 40-70 in the U.S. are at high risk of CVD but are currently invisible to the system, because genetics is not being used as part of CVD risk prediction measures.
• Statins, the standard preventative treatment, are even more effective than average on those with high polygenic risk. If the additional high-risk individuals were identified and treated with statins, around 100,000 heart attacks, strokes, and cases of fatal heart disease would be avoided over the next 10 years.

NEW ORLEANS, Nov. 10, 2025 /PRNewswire/ -- Genomics, a science-led techbio company using large-scale genetic information to develop innovative precision healthcare tools and to accelerate drug discovery and development, has today announced new research that suggests polygenic risk scores (PRS) can significantly improve the predictive performance of the cardiovascular disease (CVD) risk prediction tool, PREVENT. The findings were presented at the American Heart Association Conference 2025.¹

The research shows that adding genetic risk to CVD tools can better identify individuals at risk of heart disease, with this benefit seen across ancestries. The findings support the implementation of PRS with the next generation of clinical CVD risk predictors, adding to a growing body of evidence that PRS can help improve CVD prevention, saving patient lives and improving population health.

CVD is the leading cause of death in the U.S., claiming over 900,000 lives in 2023, accounting for approximately one in three deaths. There is one CVD death every 34 seconds, and someone has a heart attack every 40 seconds. The cost of heart disease in the U.S. in 2024 was over $400 billion.²

The key to CVD prevention is to identify people at high risk of the disease and to reduce their risk through statin therapy and lifestyle changes. The widespread use of statins for CVD prevention earlier this century has dramatically reduced CVD deaths. A meta-analysis of 25 trials involving nearly 70,000 patients with coronary heart disease found that the use of statins reduces CVD events by 25% and overall mortality by 16%.³  Previous studies had shown that adding polygenic risk to earlier clinical risk calculators significantly improves risk prediction for CVD.

Developed by the American Heart Association in 2023, the Predicting Risk of Cardiovascular Disease EVENTs (PREVENT) tool estimates risk for total cardiovascular disease (CVD) over 10 and 30 years, including atherosclerotic CVD (ASCVD) and heart failure (HF). PREVENT – the most recent ASCVD risk tool backed by the American Heart Association – currently combines cardiovascular, kidney, and metabolic health measures to guide primary prevention-focused treatment decisions.

Genetics is known to be a major risk factor for many diseases, including CVD; however, most clinical risk tools (CRTs), which use established risk factors to estimate future outcomes and guide preventive management, currently do not take genetic information into account.

The research set out to investigate whether combining polygenic risk scores with the PREVENT tool would improve its accuracy. The findings suggest that adding genetic information to an Integrated Risk Tool (IRT) significantly improves the predictive performance of the tool. The research therefore indicates that the use of such an integrated risk tool (IRT) combining a PRS with PREVENT 10-year risk for ASCVD, has clinical utility.

"Our findings show that incorporating polygenic risk scores into clinical practice can significantly improve the predictive power of tools like PREVENT across diverse populations, making risk assessment more equitable and precise. There are millions of people in the U.S. who are at high risk of heart disease who are currently not being identified because their genetic risk is being ignored," said Professor Sir Peter Donnelly, Co-Founder and CEO of Genomics. "This research moves us closer to a future where genetic information is a standard part of personalized preventative care to improve outcomes for cardiovascular disease and other serious conditions."

Using Kaiser Permanente Research Bank, the study measured the improvement in prediction accuracy using the commonly used measure of Net Reclassification Improvement (NRI). Combining the PRS with the PREVENT score improves the ability to detect those most likely to develop ASCVD (NRI = 6%).

Amongst those with PREVENT scores of 5-7.5%, just below the current risk threshold of 7.5% used for statin prescription, those with high PRS were almost twice as likely to develop ASCVD over the subsequent decade than those with low PRS (odds ratio 1.9).

The researchers found that an individualʼs risk estimate often changes substantially using the IRT versus PREVENT alone. Further, 8% of individuals aged 40-69 were reclassified as higher risk in the IRT compared to PREVENT alone. These high-risk individuals are not currently flagged by PREVENT.

Using these calculations, the researchers also found that over three million people aged 40-70 in the U.S. at high risk of CVD are currently invisible to the system, because genetics is not being used as part of CVD risk prediction measures. Statins are even more effective than average for people with high PRS. This means that over 100,000 people could avoid CVD-related complications over ten years if PRS were routinely added to PREVENT, followed by statin treatment for the newly classified high-risk individuals (compared to these individuals not being treated with statins).

This study adds to a growing body of evidence that PRS can help improve CVD management and prevention.

Genomics's 2021 HEART clinical trial, conducted with the United Kingdom's National Health Service (NHS), demonstrated that integrating genetic data into cardiovascular risk assessments fitted smoothly into clinical care pathways and changed patient management. The recently released 10-year plan for the NHS committed to rolling out prevention based on PRS to the whole country.

To learn more about Genomics, visit https://www.genomics.com/.

About Genomics

Genomics is a pioneering techbio company that uses large-scale genetic information to develop innovative precision healthcare tools and bring new understanding to drug discovery. We were formed in 2014 by four world-leading statistical and human geneticists at the University of Oxford. Today, we are collaborating with some of the world's leading healthcare organisations and helping them to predict, prevent, treat, and cure – dramatically reducing the human and financial cost of common diseases like cancer, diabetes, and heart disease.

SOURCE Genomics