Two week interruption of statin therapy results in an exaggerated inflammatory phenotype in young myocardial infarction patients without standard modifiable risk factors
Authors: Mol J H Q , Van Tuijl J , Bekkering S , Stolk-Van Der Heijden C , Damen S , Cossins B , Van Emst L , Pop G , Netea M , Van Royen N , Riksen N , El Messaoudi S 
Published: October 2022

Abstract

Background
In patients with myocardial infarction (MI) it is recommended to start high intensity statin therapy, as early as possible, irrespective of lipid levels at presentation. In ST-elevated myocardial infarction (STEMI) patients that do not have standard modifiable risk factors (SMuRFs) there is lower use of statins at discharge compared to patients with at least 1 risk factor, and this is associated with a worse prognosis. Beside lipid lowering capacities, statins are known for their anti-inflammatory effects. Atherosclerosis is characterized as an inflammatory disease in which monocytes play a pivotal role. Circulating monocytes of atherosclerosis patients with SMuRFs have a pro-inflammatory phenotype. In the absence of other modifiable factors in young SMurfless patients, targeting inflammation seems crucial. The effects of (short term) cessation of statin treatment in young SMuRFless MI patients are not known.

Purpose
The aim of this study was to assess the short term effect of cessation of statin treatment on the inflammatory profile in young SMuRFless MI patients.

Methods
We included 19 SMuRFless patients (low-density Lipoprotein cholesterol (LDLc) &lt;4.5 mmol/L), no hypertension, no diabetes mellitus, body mass index &lt;30 kg/m2) who suffered a myocardial infarction between 1 and 4 years ago at an age &lt;50 years, and were actively receiving statin therapy. Blood was drawn prior to- and after 14 days of statin cessation. At both time points we assessed circulating high sensitive-C-reactive protein (hs-CRP) levels and leukocyte counts. Using flow cytometry we determined monocyte (subset) phenotype. Monocyte function was studied by measuring cytokine production of peripheral blood mononuclear cells (PBMCs) after isolation and 24-hours incubation with Toll-like receptor (TLR) agonists.

Results
Short-term interruption of statin treatment resulted in a significant increase in circulating hs-CRP (0.6 vs 0.7 mg/L, p=0.03). Flow cytometry analysis revealed that short term cessation of statin treatment caused a shift in monocyte subset distribution (Figure 1). The CD14++CD16+ “intermediate” monocyte subset became significantly upregulated (p=0.026). Statin interruption also resulted in altered PBMC function after stimulation. No significant differences were seen in PBMCs stimulated with lipopolysaccharide (LPS). Pam3CysK4 (P3C) stimulated cells produces more IL-6 (p=0.004), IL-10 (p=0.010) and IL1Ra (p=0.047) after cessation of statin treatment (Figure 2).

Conclusions
In young SMuRFless MI patients, short-term interruption of statin treatment results in a heightened inflammatory profile, as demonstrated by elevated circulating CRP, a switch in monocyte phenotype and exaggerated monocyte cytokine production capacity. This difference was already noticeable 14 days after cessation of statin. This emphasizes the importance of statins therapy, irrespective of lipid levels or other SMuRFs.

Funding Acknowledgement
Type of funding sources: None.