Sudden death in ischemic heart disease: looking for new predictors: polygenic risk

Abstract

Abstract The phenomenon of sudden death (SD) occurs, in 70% of cases, in people who do not fall within the indications of the guidelines relating to the implantation of the defibrillator. There is a way of inheriting the risk condition by genetic means, the polygenic one, in which mutations are not found, but an increase in alleles of common variations called polymorphisms. The PRE-DETERMINE cohort study has the primary objective of determining whether biological markers, and electrocardiogram can be used to identify individuals more likely to experience SD. Within the study, we investigated the utility of the genome-wide polygenic score for coronary artery disease (GPSCAD) for SD risk stratification in an intermediate-risk population with stable coronary artery disease without severe systolic dysfunction and/or indication for an implantable cardioverter defibrillator in primary prevention. Over a mean follow-up period of 8.0 years, patients in the top decile of GPSCAD were at higher absolute (8.0% vs. 4.8%; P < 0.005) and relative (29% vs. 16%; P < 0.0003) risk of SD compared to the rest of the cohort. No association was found between the highest decile of GPSCAD and other forms of death, cardiac, and non-cardiac. The data on the increase in absolute and relative terms of SD can be used, at this stage, only for a theoretical estimate on the possible efficacy of the defibrillator in the population with chronic coronary artery disease and moderately depressed left ventricular function as number needed to treat and possible reduction of mortality in high-risk patients (those included in the top decile of GPSCAD).