AI Article Synopsis

  • - Patients with statin-resistant familial hypercholesterolemia (SR-FH) are at high cardiovascular risk, prompting the need for new treatment options like PCSK9 inhibitors (PCSK9i), which lower cholesterol levels and may affect inflammation.
  • - A study evaluated the impact of PCSK9i on inflammatory markers in 20 SR-FH patients, revealing significant reductions in LDL cholesterol and changes in pro- and anti-inflammatory cytokines after six months of treatment.
  • - The findings suggest that PCSK9i therapy can lead to subclinical anti-inflammatory effects, highlighting its potential benefits for improving patient outcomes in SR-FH cases.

Article Abstract

Background: 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.

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

Methods: 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.

Results: 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.

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

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11291198PMC
http://dx.doi.org/10.3389/fcvm.2024.1417044DOI Listing

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