The Effect of Statin Treatment on Trained Innate Immunity

Study Overview
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Brief Summary
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The innate immune system plays a pivotal role in the development and progression of atherosclerosis. Recently, it was reported that monocytes can develop a long-lasting immunological memory after stimulation with various microorganisms, which has been termed 'trained innate immunity'. This memory is induced by epigenetic reprogramming, in particular trimethylation of lysine 4 at histone 3 (H3K4me3). In this study, the investigators aim to investigate the immunophenotype of circulating monocytes in patients with elevated LDL cholesterol levels and the effect of statins on this phenotype.

Detailed Description
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The innate immune system plays a pivotal role in the development and progression of atherosclerosis. Recently, it was reported that monocytes can develop a long-lasting immunological memory after stimulation with various microorganisms, which has been termed 'trained innate immunity'. This memory is induced by epigenetic reprogramming, in particular trimethylation of lysine 4 at histone 3 (H3K4me3). The main objective is to study whether circulating monocytes of patients with elevated levels of LDL have a phenotype of trained innate immunity compared to control patients. Subsequently the investigators will study the effect of treatment with statins on the increased inflammatory response and epigenetic changes of the innate immune system.

Official Title
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Effect of Statins on Epigenetic Reprogramming of Monocytes in Patients With Elevated Levels of LDL

Conditions
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Atherosclerosis

Intervention / Treatment
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* Drug: statin treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 years or older Elevated LDL levels (>4.9 mmol/l) Decision made by treating physician to initiate statin treatment Exclusion Criteria: previous cardiovascular events.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| High-LDL<br>patients with LDL cholesterol levels of >4.9 mmo/l, who have not been treated with statins in the past years, and who have an indication for treatment with statins. | Drug: statin treatment<br>* The patients with elevated LDL receive statin treatment in the context of normal patient care (so this is NOT an intervention of the study)<br>|
| Control<br>control subjects with an LDL cholesterol level of <3.5 mmol/l | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cytokine production capacity | Cytokine production capacity of PBMC's at baseline in patients with elevated and normal cholesterol levels | baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cytokine production capacity | Cytokine production capacity of PBMC's at baseline in patients with elevated and normal cholesterol levels | Three months after start of statin treatment | 
| Epigenetic modifications in the promoter regions of the pro-inflammatory cytokines in monocytes. | Epigenetic modifications in the promoter regions of the pro-inflammatory cytokines in monocytes. | baseline | 
| Epigenetic modifications in the promoter regions of the pro-inflammatory cytokines in monocytes. | Epigenetic modifications in the promoter regions of the pro-inflammatory cytokines in monocytes. | Three months after start of statin treatment |