Atherosclerosis, Arteriosclerosis, Coronary artery disease, myocardial infarction Heart disease
Conditions
Interventions
All 250 individuals will undergo 1) if possible, a venous puncture in the acute moment of the MI to collect 5 ml of plasma and 5 ml of serum, 2) venous puncture at 6-12 weeks after the MI to collect b
Fat Attenuation Index as a measure for coronary inflammation. We will use the CAD-RADS 2.0 classification to report high risk plaque features and distinguish between non-obstructive CAD (CAD-RADS <
3) or obstructive CAD (CAD-RADS = 3). Finally, we will contact all patients by phone 2 and 5 years after the MI for clinical follow up. In 25 patients with stable chronic coronary artery disease, we w
Sponsors
Radboud Universitair Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Patients with acute MI: Age >18 yearsAdult patients with an acute MI Written informed consentControl patients with stable chronic coronary artery disease:Age > 18 yearsTreatment for chronic coronary artery disease.Written informed consent
Exclusion criteria
Exclusion criteria: Patients with acute MI: Life expectancy < 2 yearsUse of immunomodulator drugs (except NSAIDs)Auto-immune or auto-inflammatory diseaseHistory of allergic reaction to iodine-containing contrast agentsNot willing to receive information about incidental findings in blood tests and imaging (CCTA). History of CABG. History of prior myocardial infarction < 1 year Known pregnancy or breast feeding.severe stenosis or aortic/mitral valvehyperrophic obstructive cardiomyopathycontrictive pericarditis Control patients with stable chronic coronary artery disease:History of acute myocardial infarction or strokeUse of immunomodulator drugs (except NSAIDs)Auto-immune or auto-inflammatory diseaseCurrent infection with fever.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PBMC cytokine production capacity (TNF and IL-6 production following LPS stimulation), related to 1) MACE and 2) change in coronary plaque characteristics measured on a CCTA (difference between scan at 6 months and scan at 2 weeks after MI), including a) detailed plaque characteristics (high risk features etc) and b) Fat Attenuation Index. | — |
Secondary
| Measure | Time frame |
|---|---|
| PBMC cytokine production capacity of other cytokines (including IL-1b, IL-10, IL-1Ra, MCP-1) and other stimuli. Numbers and phenotype of circulating immune cells using flow cytometry to compare patients with and without MACE and to correlate this to coronary inflammation (FAI on CCTA).Proteomics and metabolomics on isolated plasma, to explore how markers of trained immunity (and the imaging markers of atherosclerosis) correlate to circulating (inflammatory) markers.In addition, we will perform deep immunological phenotyping in the subgroup of patients that develop a MACE and compare that in an exploratory analysis to a group of patients that did not develop MACE, matched for age, sex, and CVD risk factors. We can do this because we will store viably frozen PBMCs of all individuals. On the frozen cells of these patients, we will perform (bulk) RNAseq and ATACsec and assess DNA methylation patterns.Also, we will perform single cell RNA and ATAC seq on PBMCs, enriched with circulating Hematopoietic Stem Cells from 8 patients with MACE and 8 matched controls, according to the method described previously (16), to explore transcriptional and epigenetic reprogramming of hematopoietic stem cells. We will also perform RNA/ATAC seq and determination of DNA-methylation on PBMCs from all patients that underwent CCTA to correlate these markers of trained immunity with coronary inflammation, as detected by the Fat Attenuation Index on the CCTA. We will analyze how genetic variations associate with PBMC cytokine production capacity (the main trained immunity read out) in all 250 individuals. DNA samples will be genotyped with the Infinium Global Screening Array from Illumina. We will also review all echocardiograms that will be made for routine clinical practice, either at Radboudumc, or at the regional hospital where the patient is treated after the MI. We will also explore associations between the immunological parameters and parameters of heart failure. | — |
Countries
Netherlands
Contacts
Public ContactN. P. Riksen
Radboud Universitair Medisch Centrum
Outcome results
None listed