Abstract Introduction Recent research has shown that adding a polygenic risk score (PRS) for cardiovascular disease (CVD) to a conventional risk tool improved CVD risk prediction. It was later revealed that this addition also enhanced the identification of individuals at increased risk for cardiovascular (CV) events in an asymptomatic population. Objective Investigate in a regular cohort of an asymptomatic Southern European population whether adding a CVD-PRS to a traditional SCORE2, in the form of an integrated risk tool (IRT), increased the proportion of high-risk individuals with at least one major CV event compared with the SCORE2. Methods An asymptomatic Southern European population composed of 1103 individuals from the GENEMACOR study (53.4±6.9 years; 74.2% male) were followed up for a long period of 7.3±6.0 years. Of the 33 genetic variants mostly used in our CVD-PRS, only 13 variants that presented a Hazard Ratio1 for events were included. The additive PRS is the product sum of each individual's risk alleles, weighted by its effect size (HR). We constructed an IRT using the formula W1*SCORE2 + W2*PRS, where W1 and W2 are weights determined through AUC curves validation. So, IRT= 0.6*Score2 + 0.4*PRS. We divided IRT into three categories: 5%, 5%-10%, and 10%, and we used the higher. Statistical analysis was done using the R package and SPSS version 25. Results From the 60 CV events (death, myocardial infarction or acute coronary syndrome, coronary revascularisation, heart failure and stroke) that occurred at the end of follow-up, 32.2% occurred in the top 20%, i.e. in the highest percentile of PRS; 16.5% occurred in the top 10%; 8.5% in the top 5%; 5.1% in the top 3% and 3.4% in the top 1%. 42.4% of individuals in the highest category in SCORE2 presented CV events. When we used the IRT (combination of SCORE2 and PRS), the high-risk population with events significantly increased from 42.4% to 50.8% in all cases, an absolute increase of 8.4% (p=0.002). Conclusion In this study, adding genetic information to a traditional risk assessment in the form of an IRT significantly adds value in identifying those at high-risk for CV events, allowing preventive measures to be applied prematurely to such individuals at high risk with a major CV event.
Sá et al. (Sat,) studied this question.