Risk of inherited cardiac disease in relatives of out-of-hospital cardiac arrest patients - a nationwide study
M Brun Nielsen, T Skjelbred, I Thierry, M Gylling, E Casarini, F Folke, B G Winkel, J Tfelt-HansenAbstract
Background
Out-of-hospital cardiac arrest (OHCA) may be the first manifestation of an inherited cardiac disease. Quantifying risk among relatives is essential for guiding preventive family evaluation.
Purpose
In this study, we sought to estimate the absolute risk of being diagnosed with an inherited cardiac disease among first-degree relatives of OHCA patients. Furthermore, we examined whether this risk varies by the proband’s age at the time of OHCA and by the relative’s sex.
Methods
In this nationwide Danish cohort study, we identified all first-degree relatives of patients with OHCA of presumed cardiac origin between 2007 and 2021 and compared their risk of inherited cardiac disease with that of age and sex matched individuals from the general population. Diagnoses of cardiomyopathy, primary arrhythmogenic disorders, and familial hypercholesterolemia were ascertained using national health registries. Absolute risk of inherited cardiac disease was estimated using the Aalen-Johansen estimator, accounting for all-cause death as a competing risk, and stratified by the proband’s age at the time of OHCA and by sex of the relative.
Results
We included 117,800 first-degree relatives of 46,367 OHCA patients and 471,000 matched individuals from the general population. At 15 years of follow-up, the absolute risk of inherited cardiac disease was 0.6% [95% CI: 0.6-0.7] among relatives compared with 0.4% [95% CI: 0.4-0.4] in the general population (relative risk 1.6 [95% CI: 1.5-1.9]). The risk was markedly higher in relatives of young OHCA patients: 1.3% [0.9-1.7] for probands <35 years (RR 3.9 [95% CI: 2.4-6.2]) and 1.1% [0.9-1.3] for probands aged 35-50 years (RR 2.8 [95% CI: 2.1-3.7]). The excess risk attenuated among relatives of probands >50 years. Findings were consistent across male and female relatives.
Conclusions
First-degree relatives of OHCA patients have a significantly increased long-term risk of inherited cardiac disease compared with the general population, particularly when the OHCA occurs at a young age. These findings support targeted family evaluation following OHCA to enable early detection and prevention when a genetic cause is suspected.