Familial predisposition to cardiovascular disease and death in patients with an out-of-hospital cardiac arrest
Authors: Gylling M , Kroll J , Warming P E , Hansen C M , Folke F , Hansen S M , Kober L , Torp-Pedersen C , Garcia R , Tfelt-Hansen J , Weeke P 
Published: May 2023

Abstract

Funding Acknowledgements
Type of funding sources: Public hospital(s). Main funding source(s): Rigshospitalet

Introduction
Familial predisposition to cardiovascular disease (CVD) and death among patients with out-of-hospital cardiac arrest (OHCA), is sparsely described in current literature. A higher rate of events in first-degree relatives might imply an increased risk of future cardiac arrest and could provide vital improvements in prevention of sudden cardiac death. Therefore, investigation of CVD and death in family of OHCA-victims is needed.

Purpose
Determine familial predisposition to CVD and death in patients with OHCA.

Methods
This study used the nationwide Danish Cardiac Arrest Registry to identify all patients with OHCA (probands) of presumed cardiac origin from 2001-2014 and &lt;70 years of age at time of OHCA. First-degree relatives were identified using the Danish Family Relations Database. We included probands with at least one identifiable first-degree relative. Date of OHCA was defined as index for first-degree relatives. The probands were stratified in age groups (0-18, 19-29, 30-49, and 50-69 years at OHCA) and CVD and death among first-degree relatives was assessed in each group. CVD was defined as diagnosis with any ICD-10 I00-I51 code (hypertension (I10-I14) excluded) and CVD-death defined as death with CVD being the main cause. Probands were matched with a background population (1:4) on age and sex. First-degree relatives of the background population were identified and stratified similarly to those of probands. Rates of familial predisposition to CVD and death in probands was compared to the background population.

Results
We identified 5,443 probands (75% male, median age 51 years) with 16,260 first-degree relatives; 10,207 parents (48.2% fathers, median age 71 years) and 6,053 full siblings (52.7% brothers, median age 47.2 years). Parents to probands had a higher rate of CVD (27.5% vs. 21.9%), a higher mortality rate (51.4% vs. 38.4%) and death more often caused by CVD (39.9% vs. 34.1%) compared to parents of the background population (p&lt;0.001 for all). Stratified by age groups, probands in groups 19-29, 30-49 and 50-69 all had a higher rate of mortality among their parents compared to corresponding groups in the background population (bar diagram in fig.1). Siblings to probands also had a higher rate of CVD (4.9% vs. 2.9%, p&lt;0.001), a higher rate of mortality (3.5% vs. 2.0%, p&lt;0.001), and death more often caused by CVD (16.9% vs. 12.4%, p=0.19) compared to siblings of the background population. Stratified by age group, probands in groups 30-49 and 50-69 both had a higher mortality rate among their siblings compared to corresponding groups in the background population (bar diagram in fig.2).

Conclusion
Familial predisposition to both cardiovascular disease and death is more prevalent in patients with an out-of-hospital cardiac arrest compared to the background population. These results indicate that, cardiovascular disease and death of first-degree relatives is important risk factors for sudden cardiac arrest in the family.