TNF and familial hypercholesterolemia: This is illustrated by our previous study in which we demonstrated the presence of augmented PBMC cytokine production capacity and enrichment of H3K4me3 on the TNFA gene promoter, as markers for trained immunity, in patients with severe hypercholesterolemia (defined as LDL-c > 4.9 mmol/l), which persisted despite three months lipid-lowering therapy with statins [12].