Genetic information improves the prediction of major adverse cardiovascular events in the GENEMACOR population

• Published in: Genetics and molecular biology Vol. 44; no. 2; p. e20200448
• Main Authors: Mendonça, Maria Isabel, Henriques, Eva, Borges, Sofia, Sousa, Ana Célia, Pereira, Andreia, Santos, Marina, Temtem, Margarida, Freitas, Sónia, Monteiro, Joel, Sousa, João Adriano, Rodrigues, Ricardo, Guerra, Graça, Reis, Roberto Palma Dos
• Format: Journal Article
• Language: English
• Published: Brazil Sociedade Brasileira de Genética 01.01.2021
• Subjects: BIOCHEMISTRY & MOLECULAR BIOLOGY; events risk discrimination and reclassification; genetic risk score; GENETICS & HEREDITY; Human and Medical Genetics; Net Reclassification Index; secondary prevention of coronary artery disease; Traditional risk factors; genetic risk score; secondary prevention of coronary artery disease; events risk discrimination and reclassification; Net Reclassification Index; Traditional risk factors
• ISSN: 1415-4757; 1678-4685; 1678-4685
• DOI: 10.1590/1678-4685-gmb-2020-0448

The inclusion of a genetic risk score (GRS) can modify the risk prediction of coronary artery disease (CAD), providing an advantage over the use of traditional models. The predictive value of the genetic information on the recurrence of major adverse cardiovascular events (MACE) remains controversial. A total of 33 genetic variants previously associated with CAD were genotyped in 1587 CAD patients from the GENEMACOR study. Of these, 18 variants presented an hazard ratio >1, so they were selected to construct a weighted GRS (wGRS). MACE discrimination and reclassification were evaluated by C-Statistic, Net Reclassification Index and Integrated Discrimination Improvement methodologies. After the addition of wGRS to traditional predictors, the C-index increased from 0.566 to 0.572 (p=0.0003). Subsequently, adding wGRS to traditional plus clinical risk factors, this model slightly improved from 0.620 to 0.622 but with statistical significance (p=0.004). NRI showed that 17.9% of the cohort was better reclassified when the primary model was associated with wGRS. The Kaplan-Meier estimator showed that, at 15-year follow-up, the group with a higher number of risk alleles had a significantly higher MACE occurrence (p=0.011). In CAD patients, wGRS improved MACE risk prediction, discrimination and reclassification over the conventional factors, providing better cost-effective therapeutic strategies.