Effect of Statins on Trained Immunity

Rationale: 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. Here the investigators hypothesize that monocytes of patients with elevated LDL cholesterol levels show epigenetic changes compared to normocholesterolemic subjects and that this can be reversed by treatment with statins.

Objective: The main objective is to study whether patients with elevated levels of LDL show increased Histone 3 Lysine 4 trimethylation in the promoter regions of pro-inflammatory cytokines and have an augmented ex vivo Toll-Like Receptor agonist-induced cytokine production in isolated monocytes compared to controls. Subsequently the investigators will study the effect of treatment with statins on these responses.

Study design: Observational study Study population: Subjects aged >18 years who have been referred to the out-patient clinic and have LDL levels that require lipid lowering treatment and matched normocholesterolemic control subjects.

Inclusion criteria

Patients:

• 18 years or older
• Elevated LDL levels (>4.9 mmol/l)
• No previous cardiovascular events

Controls:

• Age > 18 years
• LDL cholesterol < 3.5 mmol/l
• No previous cardiovascular events

Exclusion criteria

• Current lipid lowering treatment
• Known malignant disorders, auto-immune disorder, or diabetes
• Inability or unwillingness to comply with the protocol requirements, or deemed by investigator to be unfit for the study
• Clinical signs of acute infection
• Use of anti-inflammatory medication