Sudden cardiac death risk can be determined by genetic score

By Nidhi Saha, BDSOct 3 2022Reviewed by Aimee Molineux

A recent study published in the Journal of the American College of Cardiology found that a genome-wide polygenic score for coronary artery disease (GPS_CAD) can predict sudden and/or arrhythmic death (SAD) risk in coronary artery disease (CAD) patients without severe systolic dysfunction. Thus, this assessment score may help guide indications of implantable cardioverter-defibrillator (ICD) in this group of patients.

Original Investigation: Polygenic Risk Score Predicts Sudden Death in Patients With Coronary Disease and Preserved Systolic Function. Image Credit: Lightspring / Shutterstock

Background

Researchers have conducted numerous studies to identify patients at risk for cardiovascular diseases and treat them effectively. Recently, genomics has been employed to prevent many cardiovascular, respiratory, and sleep-associated disorders. 

More than 70% of sudden deaths caused by cardiac causes are unexpected and occur in patients without a significant risk of sudden death. Recognition of early signs of cardiac arrest like chest pain, back pain, inability to breathe, dizziness, fatigue, and seeking emergency help – support of defibrillator, cardiopulmonary resuscitation, and advanced life support, can save lives. 

SAD is commonly associated with CAD, so identifying patients with a higher genetic risk for cardiac arrest can ensure these individuals have access to life-saving tools. Furthermore, some patients with CAD were found to be genetically predisposed to SAD. Hence, a common genetic basis for both these diseases is likely. 

The study

This study aimed to determine whether GPS_CAD might have utility in SAD risk stratification in CAD patients who do not have severe systolic dysfunction. 

Here, the 5,488 study participants were genotyped. A raw GPS_CAD score was determined for each participant – by multiplying the genotyping dosage for each risk factor (allele) by its weight and then summing the results of all variables of the scoring system. Ancestry-adjusted scores were derived using a linear regression model using a reference distribution from 1,000 genomes.

Results

Among the participants with European ancestry, the GPS_CAD decile of 13.8% was in the top general population. In the remaining participants, the top GPS_CAD decile comprised younger patients. The majority were females and had severe CAD, a history of coronary artery bypass surgery, and familial history of SAD. This cohort was not prone to renal function impairment.

Over the study course, the unadjusted incidence of SAD was found to be greater in the top decile of GPSCAD. While the unadjusted cumulative incidence of non-SAD deaths was considerably lower in the top GPS_CAD decile. Thus, in this subgroup, the proportion of deaths caused by SAD was comparatively greater in the top GPS_CAD decile.

When adjusted for age and sex, the participants in the top GPS_CAD decile had a 1.76-fold increased risk for SAD. Whereas controlling for left ventricular ejection fraction (LVEF), familial history of SAD, and ECG score showed identical results. 

Comparing CAD severity and renal function, SAD could be linked to CAD. The results established as the association of the top GPS_CAD decile with SAD translated into an increased risk of cardiac death.

Multivariable analyses – the difference in the association between the top GPS_CAD decile and SAD and non-SAD were statistically significant. Meanwhile, an association of the top GPS_CAD decile with non-cardiac deaths could not be established.

Inference

SAD appeared to be strongly associated with the risk score for CAD. Notably, the SAD risk was lower in the top GPS_CAD decile. Thus, this genomic scoring system could aid in the risk stratification of SAD in patients who do not qualify for ICD therapy. Another area of research is gene therapy for cardiovascular diseases – which may alter the clinical outcomes of patients with SAD.