Integrated Risk Tool Could Improve QRISK2 for IDing High Cardiovascular Risk


Data from a new study details the apparent benefit of adding polygenic risk scores to improve cardiovascular risk stratification.

Nilesh Samani, MD | Credit: University of Leicester

Nilesh Samani, MD
Credit: University of Leicester

A new study from investigators at the University of Leicester is shedding light on the impact of adding genetic information to health screenings for improving clinical risk prediction.

Leveraging data from more than 44,000 adult patients, results of the study indicate use of an integrated risk tool improved the ability of the QRISK2 clinch risk score to identify patients who would go on to experience a major cardiovascular disease event by 11.7%.1

“Our study shows that adding genetic information, which is now not expensive to obtain and can be easily integrated into the current assessment carried out by GPs and other healthcare professionals, can significantly improve the identification of those at high risk, especially among younger people where the impact of having a heart attack or stroke can be even more devastating for the individual and their family,” said lead investigator Sir Nilesh Samani, MD, professor of Cardiology at the University of Leicester and honorary consultant cardiologist at the Cardiac Centre, Glenfield Hospital.2

As technology continues to progress in tandem with a greater understanding of disease pathophysiology, the use of polygenic risk scores to improve risk stratification has become a focal point of numerous research efforts. Among those is the current study from Samani and colleagues, which sought to determine whether the addition of a polygenic risk score, known as the integrated risk tool, could improve the identification of those at increased risk in real-world settings.1

As part of the UK National Health Service Health (NHSHC) program, the Genetics and the Vascular Health Check Study (GENVASC) invites adults aged 40 to 74 years without known cardiovascular disease to attend an assessment in a general practice, undergo an assessment of risk factors, and receive a QRISK2 score.1

From 2012 to 2020, a total of 44,141 individuals aged 40 to 74 years without a history of cardiovascular disease underwent an NHSHC visit. Among this cohort, 195 adults experienced a major cardiovascular disease event during the follow-up.1

To reduce potential confounding, propensity score analyses using age, sex, ethnicity, smoking status, body mass index, and QRISK2 score were used to identify controls without replacement in an approximate 2:1 ratio to the cases. In total, 396 propensity-matched controls with a similar risk profile as the 195 cases were identified for inclusion.1

Results of the analysis indicated the QRISK2 identified 61.5% (95% CI, 54.3 to 68.4) of those who went on to experience a major cardiovascular disease event as being at high risk at their health check. In contrast, combination of QRISK2 and the integrated risk tool increased identification rate by 11.7% (P = 1×10−4) from 61.5% to 687% (95% CI, 61.7 to 75.2).1

Further analysis demonstrated combination of the tools appeared to have the greatest benefit for identifying younger patients at high risk. Among those aged 40 to 54, use of QRISK2 identified 26.0% of those who developed a major cardiovascular event as high risk compared to 38.4% (95% CI, 27.2 to 50.5), which represents a 47.7% increase in strength of identification (P = .001).1

“A really important aspect of this research with Professor Samani and his colleagues is the diversity of the study population. Crucially, the work provides real world evidence that combining genetics with the current clinical risk tools works well, and provides benefit for all the ethnicities in the study,” added Sir Peter Donnelly, DPhil, chief executive officer of Genomics plc—the company who developed the integrated risk tool.2


  1. Samani NJ, Beeston E, Greengrass C, et al. Polygenic risk score adds to a clinical risk score in the prediction of cardiovascular disease in a clinical setting. Eur Heart J. Published online June 7, 2024. doi:10.1093/eurheartj/ehae342
  2. University of Leicester. Adding genetic information to health checks improves identification of people at risk of heart attacks and strokes: News. University of Leicester. June 11, 2024. Accessed June 18, 2024.

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