Polygenic Risk Score Predicts Risk for Sudden Cardiac Death
Researchers at the Smidt Heart Institute at Cedars-Sinai have developed a polygenic risk score (PRS) that helps predict which cardiovascular disease patients are at increased risk of sudden and/or arrhythmic death.
Roopinder Sandhu, M.D., associate professor of Cardiology at the Smidt Heart Institute, and colleagues eventually hope to add this score to standard assessment to help inform healthcare providers who may need extra monitoring or treatment.
“In order to better predict and prevent sudden cardiac death, we must first understand the genetic connection between it and coronary artery disease,” said Sandhu, who was also the first author of the Journal of the American College of Cardiology paper describing the study, in a press statement.
“We found incorporating information from this genetic risk score improved our ability to predict sudden death beyond the contributions of other known risk markers…the genetics were able to identify patients where sudden death was more likely to limit their life expectancy.”
Sudden cardiac death, often linked to undiagnosed arrhythmias or known coronary disease, is an ongoing problem and is responsible for up to 20% of all deaths.
In those with known coronary artery disease, implantable cardioverter defibrillator (ICD) devices can improve survival, but more than 70% of these deaths occur in individuals who do not qualify for implantation of these devices. For this reason, improving risk prediction among individuals with cardiovascular disease is important.
The current study generated a PRS based on genomic data from 4,698 individuals of European ancestry with coronary artery disease and a left ventricular ejection fraction in the 30–35% range.
Those individuals with the highest PRS scores (top 10%) had significantly increased risk for sudden and/or arrhythmic death, with an increase in risk compared with the general population of 77% when possible confounding factors such as left ventricular ejection fraction, clinical factors, and electrocardiogram parameters were accounted for. It did not predict other forms of death, however.
“It is feasible that those in the highest decile of [the PRS score] may have a greater burden of rupture-prone atherosclerotic plaques that are more likely to rapidly transition from stable CAD to an unstable pathophysiology,” write the authors.
“Alternatively, there may also be pleiotropic effects on adverse myocardial scar and/or ion channel remodeling that might increase the predisposition toward fatal arrhythmias,” they suggest.
When the researchers added the PRS score to other risk factors the overall grouping was improved and those at highest risk highlighted.
“This study indicates there is an opportunity to identify patients at highest risk for sudden cardiac death, and then offering meaningful, preventative treatment solutions like a defibrillator. Based on our pivotal research, we now have the foundation to achieve this,” emphasized lead author Christine Albert, chair of the Department of Cardiology in the Smidt Heart Institute.