Prognostic change of adding coronary calcium score and genetic risk score to European SCORE2 in a moderate risk region

Abstract

Abstract Introduction Cardiovascular disease is a public health issue remaining the leading cause of death worldwide. One of its main contributors is coronary artery disease (CAD), a complex multifactorial disease with the influence of hereditary and environmental factors. It’s crucial to improve cardiovascular risk assessment which is a real challenge in our daily clinical practice. SCORE 2 enhanced the identification of individuals at higher risk of developing CAD, but it remains scanty. Coronary Artery Calcification (CAC) score and Genetic contributions could improve CV risk stratification in primary prevention. Purpose Evaluate the impact of including CAC score and Genetic Risk Score (GRS) to the European SCORE2 in MACE prediction and cardiovascular risk stratification in our asymptomatic population. Methods 945 asymptomatic subjects (mean age 52.9±6.8 years, 74.0% male) selected from the prospective arm of the GENEMACOR study were followed up during 5.4±4.1 years. The population was categorized according to SCORE2 into three risk groups (low-intermediate <5%; high 5-10%; very high >10%). CAC score was performed by cardiac computed tomography and reported as Agatston units according to the Hoff Nomogram in low, moderate and high-risk categories. The GRS was created from 33 genetic variants associated with CAD by GWAS, choosing those with a hazard ratio (HR) higher than 1. Multivariable Cox proportional hazard ratios (HR) with 95% confidence intervals (95% CI) assessed the variables independently associated with CV events occurrence. We evaluated the discriminative ability of the Score2, CAC score and GRS using the Harrel C statistics. Results Cox regression analysis showed that the highest categories of SCORE2, CAC and GRS remained in the equation with an HR of 16.6 (p=0.008), HR of 3.6 (p=0.006) and HR of 3.2 (p=0.022), respectively, when compared with the lowest categories. C-statistic demonstrated that the predictive value for MACE was 0.671 for SCORE2, increased to 0.799 (p=0.002) when adding CAC score and improved to 0.808 (p=0.012) when adding mGRS (Table 1), showing a better discrimination capacity for MACE. Conclusions Our results highlight the importance of adding CAC score and GRS to SCORE2 in primary prevention to improve cardiovascular risk stratification and MACE prediction. Larger prospective multicenter cohorts with longer follow-up should reproduce and validate these findings.