To investigate the innate pro-inflammatory response in young patients (
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 endpoint is H3K4 trimethylation in the promoter region of
inflammatory cytokines and the genetic search for the exonic variant, which can
be correlated to the exaggerated pro-inflammatory response.
Secondary outcome
Secondary endpoints are the cytokine release by monocytes in response to
stimulation with Toll-like Receptor(TLR)-agonists and the transformation of
monocytes in foam cells. Also the specific blood platelet function in these
patients will be examined.
Background summary
A number of patients suffers from a myocardial infarction (MI) despite the
absence of the *classical* risk factors for atherosclerosis; we consider them
to be *the unhappy few*. Numerous studies have shown that atherosclerosis is a
chronic inflammatory disease and we hypothesize that these *unhappy few* have
an (epi-)genetic predisposition of an exaggerated innate pro-inflammatory
response, which accelerates the process of atherosclerosis.
Study objective
To investigate the innate pro-inflammatory response in young patients (<50
years of age), who suffer from a myocardial infarction. The pro-inflammatory
response will be examined by the search for *trained immunity* especially in
the monocytes of peripheral blood, which leads to a more vigorous reaction and
to more production of pro-inflammatory cytokines. At the same time the function
of platelets in peripheral blood will be examined, as platelets form part of
the inflammatory response. Furthermore, the bacteria present in the acute
ruptured plaque within the culprit-coronary will be compared by DNA-analysis
with the bacterial spectrum, present in the intestinal microbiota. Examining
the specific pro-inflammatory response in young patients without classical risk
factors may also lead to discover those genetic traits, which determine the
inflammatory role in atherosclerosis. The presence of these genetic traits is
probably difficult to find in the usual MI patients with classical risk factors
but might become more visible in these young *unhappy few*.
Study design
Single-center, prospective, observational study
Study burden and risks
In the patients 10 tubes of peripheral blood (4x10 cc, 2x3 cc, 1x3cc, 1x5 cc,
1x2 cc en 1x2,5 cc) will be taken in the prehospital phase, 12 hours after
hospitalization and after 1 month during their out-patient visit. On the second
or third day also 2x10 cc peripheral blood will be taken for genetic analysis.
Also faeces and saliva will be collected within the first 48 hours of
hospitalization. From the first degree relatives of each patient only once 4
tubes of peripheral blood will be taken as well as once collection of faeces
and saliva. Also in the 20 matched healthy volunteers, who are not related to
patients who suffered from a myocardial infarction. 4 tubes of peripheral blood
and once a portion of faeces will be taken. The examination of the siblings
might reveal increased risk for atherosclerotic events, from which they might
benefit by getting early preventive treatment.
Geert Grooteplein Zuid 10
Nijmegen 6525GA
NL
Geert Grooteplein Zuid 10
Nijmegen 6525GA
NL
Listed location countries
Age
Inclusion criteria
Cases:
Twenty patients aged between 18 and 50 year, who present with an acute ST-elevation myocardial infarction eligible for primary percutaneous coronary intervention. ;Family members:
Forty of their first degree healthy family members of the patients presenting with the acute myocardial infarction (two family members per patient).;Controls:
20 healthy controls aged 18 years or above. Controls will be matched with the cases for age, gender and cardiovascular risk factors.
Exclusion criteria
Cases:
- If the index patient (suffering from the acute myocardial infarction) has one or more of the following factors present:
o Age below 18 years
o Diagnosis of vascular disease (e.g. previous myocardial infarction, CVA, etc)
o Use of statins, anti-inflammatory agents or thrombocyte aggregation inhibitors (these drugs modulate epigenetic changes in in vitro studies)
o Auto-immune diseases (e.g. rheumatoid arthritis)
o Coagulation disorder
o No living first degree family members aged 18 years or above
o Presence of two or more of the following risk factors:
§ Hypertension
§ Hypercholesterolemia
§ Diabetes mellitus
§ Active smoking or an active smoking history within the last 10 years;Family members:
- If the first degree relative (i.e. the participant) has one or more of the following factors present:
o Age below 18 years
o History of vascular disease (e.g. previous myocardial infarction, CVA, etc)
o Use of statins, anti-inflammatory agents or thrombocyte aggregation inhibitors (these drugs modulate epigenetic changes in in vitro studies)
o Signs or symptoms of a current infection (fever, chills)
o Auto-immune diseases (e.g. rheumatoid arthritis)
o Coagulation disorder
Controls:
- If the control has one or more of the following factors present:
o Age below 18 years
o History of vascular disease (e.g. previous myocardial infarction, CVA, etc)
o A first degree family member with vascular disease (e.g. previous myocardial infarction, CVA, etc)
o Family relationship with the cases
o Use of statins, anti-inflammatory agents or thrombocyte aggregation inhibitors (these drugs modulate epigenetic changes in in vitro studies)
o Signs or symptoms of a current infection (fever, chills)
o Auto-immune diseases (e.g. rheumatoid arthritis)
o Coagulation disorder
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 | NL49740.091.14 |