Epigenetic Biomarkers in Sudden Cardiac Arrest

The causes of out-of-hospital cardiac arrest (OHCA) are highly complex and not
fully resolved. To elucidate these causes, we set up the ongoing ARREST study,
a community-based study in which consecutive victims of all-cause OHCA in one
contiguous region (N-Holland province) are registered and their medical data
and environmental factors are collected. We also collect a biobank of DNA
samples extracted from residual blood samples taken after OHCA for patient care
in order to study genetic factors that contribute to OHCA. In the present
study, we aim to test the hypothesis that epigenetic factors also contribute to
OHCA risk. This hypothesis stems from indications that OHCA risk is partly
determined by environmental factors such as diet, smoking or
socio-economic/psychosocial stress; these factors impact on the human genome by
altering its transcriptional regulation. To test this hypothesis, we plan to
analyse the epigenetic profiles of the DNA samples in the biobank. However, a
potential difficulty is the fact that these samples were obtained after OHCA
had already occurred, while it is unknown whether OHCA per se alters the
epigenetic profile. If so, the epigenetic profile found in these samples is
confounded by the effects of OHCA, rendering it unclear to which extent they
also caused OHCA. To rule out this possibility, we plan to conduct the present
study, in which we compare the epigenetic profiles from 15 study participants
of samples in the biobank with samples that will be collected at least 9 months
after OHCA. We assume that the OHCA-induced changes in epigenetic profiles (if
at all present), will have abated, and the epigenetic profiles will have
returned to their pre-OHCA values by that time.

To study whether epigenetic profiles of study participants who suffered an
out-of-hospital cardiac arrest (OHCA) that were collected immediately after
OHCA (in ARREST biobank) are similar their epigenetic profiles collected at
least 9 months after OHCA. This is done to determine whether the epigenetic
profile is a cause, rather than the result of the OHCA.

Cohort study of 15 adult study participants who suffered an out-of-hospital
cardiac arrest (OHCA). The epigenetic profiles of their DNA samples previously
collected and stored in the ARREST biobank will be compared to newly collected
DNA samples taken at least 9 months after OHCA.

Participation in the trial means that the study participant has to answer
questions about their smoking habits, medication use and socio-economic status.
Study participants will have their blood drawn once. Their visit for this study
will be combined with their regular visit to the cardiology outpatient clinic
as much as possible. There are no direct benefits for the study participant.
Minimal risks (associated with one-time blood draw) are associated with this
intervention. However, the benefits for the population could be large.