Stress-induced immune reprogramming in cardiovascular disease (STRESS-CVD)

Cardiovascular diseases (CVD), including stroke, myocardial infarction, and
peripheral arterial disease, are the main cause of mortality worldwide. The
majority of CVD is caused by atherosclerosis, which is a chronic low-grade
inflammatory disorder of the arterial wall. Innate immune cells, including
monocytes and macrophages, importantly contribute to the pathophysiology of
atherosclerosis.
In this study, we will investigate the effects of perceived psychosocial stress
on the innate immune system and arterial wall inflammation in patients with
heightened risk for CVD. Epidemiological studies have well-established that
psychosocial stress is an independent risk factor for atherosclerotic CVD. The
exact mechanism mediating this association, however, remains incompletely
understood. Preclinical studies have suggested that stress leads to a prolonged
hyperresponsiveness of innate immune cells by (epigenetic) reprogramming of
their progenitor cells, but this has never been tested in humans.

To investigate whether high perceived stress is associated with inflammatory
reprogramming of innate immune cells and their bone marrow progenitors, and
with increased arterial wall inflammation, in subjects with an increased CVD
risk.

An observational cross-sectional study.

none

Participants will not benefit from participating in this study. With their 
participation they 
can help the researchers to gain more insight into how stress can predispose 
individuals to CVD. This will not only enhance our understanding of how stress 
affects atherosclerotic CVD, but could also unveil potential novel treatment 
targets to lower CVD risk in patients at high stress levels. 

Potential risks are described below for all procedures separately.

• Blood draw: In total 52 ml blood will be obtained, which is not expected to 
result in side effects. Risks of vena puncture are hematoma formation and minor 
pain. This will be minimized by having vena puncture performed by experienced 
nurses or physicians.

We thus feel that the risks and burdens to the subjects are proportional to the 
potential value of this study, which will deliver ground breaking insight into 
the mechanisms of how trained immunity is induced the context of psychosocial 
stress. Duration of the procedure: 10 minutes.

• FDG PET-CT imaging The PET/CT scan will result in an effective radiation 
dose of 3.0 (PET) + 5.2 (CT) = 8.2 mSv (also see Radiation Ethics Form). In 
line with Risk Category IIb, the proposed study will significantly contribute 
to increased knowledge on how stress can affect CVD by impacting on the immune 
system, by a process named trained immunity. This mechanism contributes to the 
subsequent acceleration of atherosclerosis throughout the body and subsequent 
cardiovascular events. Knowledge on this mechanism and on how this mechanism 
can be non-invasively detected by PET scanning, will contribute to the 
development of novel pharmacological strategies to reduce cardiovascular 
disease. Given the potential benefits or our results, we think this radiation 
exposure is proportional.
Duration of the procedure: 4 hours.