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

Conditions: atherosclerosis
cardiovascular disease
10003216

Registration Number: NL-OMON53178

Lead Sponsor: niversitair Medisch Centrum

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 125

Inclusion Criteria

In order to be eligible to participate in this study, a subject must meet all
of the following criteria:
- Age 40-70 years
- Heightened cardiovascular risk, defined as a moderate to high risk for CVD
(>7.5% 10 year ASCVD risk, according to American College of Cardiology (ACC)
AtheroSclerotic Cardiovascular Disease (ASCVD) risk calculator
(https://tools.acc.org/ASCVD-Risk-Estimator-Plus/#!/calculate/estimate/) or
patients with subclinical ASCVD on imaging (e.g. elevated CAC or asymptomatic
coronary artery stenosis).
- Written informed consent

Exclusion Criteria

A potential subject who meets any of the following criteria will be excluded
from participation in this study:
• Previous cardiovascular events (stroke, TIA, myocardial infarction)
• Heart failure
• Auto-inflammatory or auto-immune diseases
• Use of immunomodulating drugs
• Severe renal failure (MDRD <30)
• Previous vaccination within 1 months prior to study entry.
• Current infection or clinically significant infections within 1 months before
participation (defined as fever >38.5).
• Pregnancy/lactation
• Severe psychiatric disorder.
• Inability to undergo PET-CT scanning
• History of hematological malignant disease
• Documented bleeding diathesis or thrombocytopenia <50 *10e9/L

Study & Design

Study Type: Observational invasive

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>All 125 included patients will fill out questionnaires and donate blood. In the<br /><br>subgroup of 25 patients with highest and lowest perceived stress according to<br /><br>the PSS10 questionnaire, we will also perform 18F-fluorodeoxyglucose<br /><br>(FDG)-Positron Emission Tomography (PET)/CT scanning, and perform bone marrow<br /><br>aspiration to obtain hematopoietic stem and progenitor cells (HSPCs). The<br /><br>primary outcome is the ex vivo production of TNF by isolated Peripheral Blood<br /><br>Mononuclear Cells (PBMCs). </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Additional study parameters are flow cytometry, and (single cell) RNA and ATAC<br /><br>sequencing of circulating immune cells and bone marrow HSPCs, and FDG-uptake in<br /><br>the arterial wall and bone marrow.</p><br>