The main objective of this study is to compare the function and phenotype of bone marrow HSPC*s in AMI patients to those of healthy control subjects.
ID
Source
Brief title
Condition
- Coronary artery disorders
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary study parameter is GM-CFU of bone marrow HSPCs (=function)
Secondary outcome
The secundary study parameter is flow cytometry of HSPCs (=phenotype) from bone
marrow and blood
Background summary
Atherosclerosis is the main cause of cardiovascular disease, including acute
myocardial infarction (AMI). It is a progressive disease, resulting in the
formation of plaques in the vessel wall. After a long asymptomatic period,
patients with atherosclerosis can present with symptoms of impaired blood flow
due to stenosis (e.g. stable angina pectoris) or with an acute event due to
plaque rupture (e.g. AMI).
Studies have consistently shown that patients with an AMI have an elevated risk
of recurrence of this event. A pathophysiological explanation is that an acute
cardiovascular event exacerbates atherosclerosis by inducing a systemic
inflammatory response. In brief, an acute cardiovascular event triggers the
release of hematopoietic stem and progenitors cells (HSPC*s) from the bone
marrow (BM) and spleen, resulting in an increased number of activated monocytes
in the circulation. These monocytes play a major role in the progression of
atherosclerosis, contributing to destabilisation of pre-existent
atherosclerotic plaques Furthermore, studies have shown that in mice with an
ischemic event bone marrow CD11b+ myeloid cells are increased compared with
naive control mice.
Unpublished data (F. van der Valk et al) shows increased BM activity in
patients is still present after several months after an acute ischemic event.
Study objective
The main objective of this study is to compare the function and phenotype of
bone marrow HSPC*s in AMI patients to those of healthy control subjects.
Study design
This study is designed as a single centre observational study. The study
consist of 1 study visit for healthy controls. Healthy controls will undergo a
bone marrow puncture to harvest bone marrow cells. These procedure will be
performed when the patient is already anesthetized for elective surgery or
under local anaesthetics in case of no elective surgery. The total duration of
this procedure will be around 30-60 minutes before the operation. HSPC*s from
AMI patients will be obtained from the historical HEBE cohort.
Study burden and risks
The results of this study contribute to the general understanding of the
mechanism by which an acute cardiovascular event elicits a systemic
pro-inflammatory state which in turn may contribute to the high risk of
recurrence. Individual subjects will gain no direct benefit from this study.
The risk of participating in this study is estimated to be low. Complications
of a bone marrow puncture are rare, a bleeding or an infection may occur.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
- Age: >34 years old (mean age 57 years)
- Gender: subjects of either gender (85% male)
- BMI between 18 and 33 kg/m2
Exclusion criteria
- Clinically evidence or at increased risk for cardiovascular disease or diabetes
- Clinically evidence for chronic inflammation
- Use of any cardiovascular medication, including but not limited to lipid-lowering therapy, antihypertensive drugs, antidiabetic drugs, platelet aggregation inhibitors and anticoagulants
- Any other known systemic disorder such as hepatic, renal, hematologic, and malignant diseases or any clinically significant medical condition that could interfere with the conduct of the study in the opinion of the investigator.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL53093.018.15 |