The risk of sudden cardiac death can be determined using the genetic score

The risk of sudden cardiac death can be determined using the genetic score

A recently published study in the Journal of the American College of Cardiology found that a genome-wide polygenic score for coronary artery disease (GPSCAD) can predict the risk of sudden and/or arrhythmic death (SAD) in patients with coronary artery disease (CAD) without severe systolic dysfunction. Therefore, this assessment score may help determine the indications for an implantable cardioverter-defibrillator (ICD) in this patient population.

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 disease and to treat them effectively. Recently, genomics has been used to prevent many cardiovascular, respiratory, and sleep-related disorders.

More than 70% of sudden deaths from cardiac causes are unexpected and occur in patients who are not at significant risk of sudden death. Recognizing early signs of cardiac arrest such as chest pain, back pain, shortness of breath, dizziness, fatigue and seeking emergency help - support with defibrillator, cardiopulmonary resuscitation and advanced life support can save lives.

SAD is often associated with CAD, so identifying patients at higher genetic risk for cardiac arrest can ensure these individuals have access to life-saving resources. In addition, some patients with CAD have been found to be genetically predisposed to SAD. Therefore, a common genetic basis for these two diseases is likely.

The study

This study aimed to determine whether GPSCAD could be useful in SAD risk stratification in CAD patients who do not have severe systolic dysfunction.

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The 5,488 study participants were genotyped here. A raw GPSCAD score was obtained for each participant - by multiplying the genotyping dose for each risk factor (allele) by their weight and then summing the results of all variables in the scoring system. Ancestry-adjusted scores were derived using a linear regression model using a reference distribution of 1,000 genomes.

Results

Among participants with European ancestry, the GPSCAD decile was at the top of the general population at 13.8%. For the remaining participants, the top GPSCAD decile included younger patients. The majority were women and had severe CAD, a history of coronary artery bypass graft surgery, and a family history of SAD. This cohort was not susceptible to impaired renal function.

Over the course of the study, 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 significantly lower in the top GPSCAD decile. Thus, in this subgroup, the proportion of deaths caused by SAD was comparatively larger in the top GPSCAD decile.

Adjusted for age and gender, participants in the top GPSCAD decile had a 1.76-fold increased risk of SAD. While control of left ventricular ejection fraction (LVEF), family history of SAD and ECG score showed identical results.

When comparing CAD severity and kidney function, SAD could be associated with CAD. The results found as the association of the top GPSCAD decile with SAD resulted in an increased risk of cardiac death.

Multivariable analyzes - the difference in association between the top GPSCAD decile and SAD and non-SAD was statistically significant. However, an association of the top GPSCAD decile with non-cardiac deaths could not be established.

Inference

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

Reference:

• Sandhu, R., Dron, J., Liu, Y., et al. (2022). Polygenic Risk Score sagt plötzlichen Tod bei Patienten mit Koronarerkrankung und erhaltener systolischer Funktion voraus. Zeitschrift des American College of Cardiology. Doi: 10.1016/j.jacc.2022.05.049, https://www.sciencedirect.com/science/article/pii/S0735109722054183?via%3Dihub

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