# Expression of pro- and anti-inflammatory cytokines during anti-proprotein convertase subtilisin/kexin type 9 therapy in patients with statin-resistant familial hypercholesterolemia

## TL;DR

This study shows that PCSK9 inhibitors reduce harmful inflammation and cholesterol in patients with statin-resistant familial hypercholesterolemia.

## Contribution

The study demonstrates the anti-inflammatory effects of PCSK9 inhibitors in a specific patient group with statin resistance.

## Key findings

- Six-month PCSK9i therapy significantly reduced LDL cholesterol levels.
- PCSK9i increased anti-inflammatory IL-4 and decreased pro-inflammatory TNF-alpha and MCP-1.
- No significant changes were observed in other inflammatory markers.

## Abstract

Some clinical dyslipidemia cases do not respond to statins, known as statin-resistant familial hypercholesterolemia (SR-FH), in which patients are under a high cardiovascular risk despite statin therapy. Therefore, novel therapeutic alternatives are required. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) reduce cholesterol levels and cardiovascular disease risk, particularly in patients with SR-FH, where PCSK9i may differentially affect pro- and anti-inflammatory mediators depending on the clinical setting.

To evaluate the effect of PCSK9i treatment on pro- and anti-inflammatory cytokines in patients with SR-FH.

Before–after comparison, quasi-experimental, single-center study in patients with SR-FH. Blood samples were processed to obtain complete blood counts of glycated hemoglobin and serum lipid levels. Flow cytometry was performed to characterize baseline circulating M1- and M2-macrophages and monocytes. Multiplexing of plasma samples was used to compare plasma fraktaline, interleukins (ILs), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor (TNF)-alpha. The endpoints were lower serum lipid levels and pro-inflammatory mediator modification.

Twenty patients with SR-FH, aged 58 years and most of them males, were included, with a mean body–mass index of 26.4 and showing ischemic heart disease and similar values of baseline M1- and M2-macrophages and monocytes. Six-month iPSCK-9 therapy considerably reduced LDLc, increased anti-inflammatory cytokine (IL-4), and modified pro-inflammatory cytokine (TNF-alpha and MCP-1) levels. No notable effects were observed for the other markers.

PCSK9i therapy exerted subclinical anti-inflammatory and anti-atherogenic effects, indicating potential benefits for clinical outcomes.