Polygenic Risk Scores Can Predict Chance of Sudden Cardiac Death

A polygenic risk score capable of assessing genetic risk of coronary artery disease (CAD) can also accurately predict a patient’s risk of sudden and/or arrhythmic cardiac death. That is the conclusion of a new study by researchers from Cedars-Sinai Medical Center published in the Journal of the American College of Cardiology on Aug. 30.

The Diagnostic Challenge

Unlike myocardial infarction (heart attack), which is typically caused by clogged coronary arteries reducing blood flow to the heart muscle, sudden cardiac death, aka, sudden cardiac arrest, is often caused by the sudden onset of erratic electrical activity that keeps the heart from pumping. As the name suggests, it strikes with little to no warning and, unless immediate resuscitation is provided, has fatal results.

According to a 2018 Arrhythmia & Electrophysiology Review paper, sudden cardiac death is responsible for approximately 180,000 to 300,000 deaths in the US each year and 15 percent to 20 percent of all deaths worldwide.

One major problem is that CAD, the leading cause of sudden cardiac death, is often not diagnosed. According to the study authors, 70 percent of cardiac deaths occur in patients who do not meet current guidelines for prevention with defibrillator therapy. It is only after patients go into cardiac arrest that they become aware of their coronary problems. Accordingly, prospective genetic testing based on risk factors rather than signs or symptoms has the potential to save lives.

The Cedars-Sinai Study

To better predict and prevent sudden cardiac death, we must first understand its genetic connection to CAD, noted first study author, associate professor of cardiology Roopinder Sandhu, MD, MPH. The close association between the two suggests that CAD and sudden cardiac death may share a common genetic basis. So, the team set out to determine whether factoring an individual’s polygenic risk score for CAD would improve the accuracy of predicting sudden cardiac death.

The researchers generated a genome-wide polygenic risk score for CAD in 4,698 participants of European ancestry who had CAD and other risk factors for sudden cardiac death, including a left ventricular ejection fraction of greater than 30 percent to 35 percent. They found that:

• Individuals with the highest polygenic risk scores for CAD also had higher-than-usual risk of sudden cardiac death over a median follow-up time of eight years;
• Absolute risk of sudden cardiac death was 8 percent higher for the 646 individuals in the group with the highest risk scores; and
• Proportional risk of sudden cardiac death was 29 percent, as compared to 16 percent in the other risk score groups.

Even after accounting for left ventricular function, clinical factors, and electrocardiogram parameters, they found that patients in the top polygenic score group had a 77 percent increased risk for sudden cardiac or arrhythmic death.

However, there was no association between the top group and non-sudden or arrhythmic death, even when limited to cardiac causes. According to the researchers, this suggested that the score specifically predicts sudden cardiac death and not other forms of cardiac mortality in patients with coronary artery disease.

Takeaway

The Cedars-Sinai study suggests that use of polygenic risk scores can improve clinicians’ ability to identify individuals at high risk of sudden cardiac death, a revelation that could ultimately save thousands of lives.

“We found incorporating information from this genetic risk score improved our ability to predict sudden death beyond the contributions of other known risk markers,” noted Sandhu in a statement. “Most exciting, the genetics were able to identify patients where sudden death was more likely to limit their life expectancy.”