Polygenic score predicts sudden death in CAD patients without severe systolic dysfunction
08 Sep 2022
A high genome-wide polygenic score for coronary artery disease (GPSCAD) among CAD patients without severe systolic dysfunction is independently associated with sudden and/or arrhythmic death (SAD), a recent study has shown.
GPSCAD may help identify individuals who might benefit from defibrillator therapy, the authors said.
In this study, the authors generated a previously validated GPSCAD using genome-wide genotyping in 4,698 PRE-DETERMINE participants of European ancestry with CAD and left ventricular ejection fraction >30‒35 percent. They divided the participants according to top GPSCAD decile as defined by the general population.
Finally, the authors performed competing risk analyses to estimate the absolute, proportional, and relative risks for SAD and non-SAD.
Over a median follow-up of 8.0 years, participants in the top GPSCAD decile exhibited a higher absolute SAD risk (8.0 percent, 95 percent confidence interval [CI], 5.1‒12.4 vs 4.8 percent, 95 percent CI, 3.3‒7.0; p=0.005) and proportional SAD risk (29 percent vs 16 percent; p=0.0003) compared with the remainder.
The top GPSCAD decile correlated with SAD (subdistribution hazard ratio [sHR], 1.77, 95 percent CI, 1.23‒2.54; p=0.002), but not non-SAD (sHR, 1.00, 95 percent CI, 0.80‒1.25; p=0.98) after controlling for left ventricular ejection fraction, clinical factors, and electrocardiogram parameters (p=0.003 for Δ).
Notably, adding the top GPSCAD decile to the multivariable model led to significant improvements in net reclassification indexes (NRIs; continuous NRI, 14.0 percent; p=0.024; categorical NRI, 6.6 percent; p=0.005), but not in the C-index (difference in C-index, 0.007; p=0.143).