A polygenic risk score added to a QRISK®2 cardiovascular disease risk calculator demonstrated robust clinical acceptance and clinical utility in the primary care setting (EJPC 2024)

PRS-enhanced risk tools that combine polygenic risk scores (PRS) with established cardiovascular disease (CVD) risk factors have been shown to improve prediction and stratification of individuals’ future risk of CVD compared with conventional risk prediction tools. However, current European Society of Cardiology (ESC) guidelines do not recommend their routine use in clinical practice, citing the absence of prospective outcomes trials, uncertainty regarding clinical benefit, and a lack of empirical evidence on how PRS can be implemented within routine care settings [1]. Against this backdrop, Fuat et al. [2] address these evidence gaps by conducting a prospective, pragmatic implementation study evaluating the real-world feasibility, acceptability, and clinical impact of integrating a PRS-enhanced risk tool into routine primary care across practices in the United Kingdom. 

The study was conducted across 12 National Health Service (NHS) general practices and enrolled 832 participants undergoing standard NHS Health Checks. The participants were 98% white, had a mean age of 55 years, and were 62% female. Both the conventional QRISK2 [3] 10-year CVD risk estimate, derived from established clinical risk factors such as age and blood pressure, and a PRS-enhanced risk tool providing an updated 10-year absolute risk estimate, were returned to healthcare providers and discussed with patients during routine primary care consultations. The primary outcome was feasibility of implementation, assessed through operational metrics and structured surveys of healthcare providers and participants, while secondary outcomes included changes in estimated CVD risk and changes to planned clinical management. 

The authors found that implementation of the PRS-enhanced risk tool was operationally feasible, with PRS-enhanced risk reports successfully generated for 100% (832/832) of participants and 93% returned within 90 days (median turnaround time 60 days).

Acceptability was high among both clinicians and patients: 91% of healthcare providers reported that the tool could be incorporated straightforwardly into routine primary care, and 74% reported they were likely to recommend the tool to colleagues in other practices. Among 520 study participants (63%) who completed a follow-up questionnaire, 99% reported the tool to be personally useful and 95% found the results easy to understand. There were no meaningful differences in responses by age, sex, or education level. 

With respect to secondary outcomes, incorporation of genetic information led to reclassification of 86 participants (11.2%) across the NICE high-risk threshold of 10% -- the level at which statin therapy is typically recommended -- with 5.2% up classified to high risk and 5.2% down classified to low risk. Among participants whose PRS-enhanced risk estimate exceeded their QRISK2 score (n = 388), clinicians reported planned changes in preventive management in 28% of cases, rising to 47% when the absolute increase in estimated risk exceeded 2%.  

Overall, the findings demonstrate that incorporation of a PRS-enhanced risk tool into routine primary care is operationally feasible and well accepted by both healthcare professionals and patients, and that provision of genetically informed risk estimates can influence planned preventive management, particularly among individuals near guideline treatment thresholds. These findings address key implementation-related uncertainties highlighted by current ESC guidance, namely whether PRS-informed risk tools can be delivered within existing primary care workflows and meaningfully incorporated into shared clinical decision-making. 

However, the authors acknowledged several important limitations. The study was conducted in a relatively small, geographically limited, and predominantly White population, and was not designed to assess clinical outcomes or cost-effectiveness. Patient perceptions of utility were based on a subset of participants who completed a follow-up survey, introducing the potential for response bias if individuals who were more engaged or motivated were more likely to report favourable views of the intervention. Changes in management were clinician-reported intentions rather than observed treatment initiation. In addition, the turnaround time for genetic testing, while acceptable within a research setting, may limit scalability in routine practice, and the generalisability of the findings to more diverse populations remains uncertain. 

In summary, the study represents a valuable first step in moving beyond predictive performance metrics toward real-world evaluation of feasibility and clinical integration of PRS-enhanced risk tools, especially as other prospective implementation studies remain limited [4,5]. 

Further research, including larger and more diverse implementation studies, economic evaluations, and prospective trials assessing downstream clinical outcomes, will be required to determine whether PRS-enhanced risk tools can meaningfully improve cardiovascular prevention beyond existing guideline-based approaches.