Endothelial function improvement in patients with familial hypercholesterolemia receiving PCSK-9 inhibitors on top of maximally tolerated lipid lowering therapy

Alessandro Di Minno, Marco Gentile, Gabriella Iannuzzo, Ilenia Calcaterra, Maria Tripaldella, Benedetta Porro, Viviana Cavalca, Maria Donata Di Taranto, Elena Tremoli, Giuliana Fortunato, Paolo Osvaldo Federico Rubba, Matteo Nicola Dario Di Minno

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Treatment with protein convertase subtilisin kexin type 9 inhibitors (PCSK-9i) reduced cholesterol levels and cardiovascular events in patients with hypercholesterolemia. We assessed changes in lipid profile, oxidation markers and endothelial function in patients with familial hypercholesterolemia (FH) after a 12-week treatment with a PCSK-9i. Methods: Patients with FH starting a treatment with PCSK-9i were included. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), lipoprotein(a) (Lp(a)), small dense LDL (assessed by LDL score), 11-dehydro-thromboxane (11-TXB2), 8-isoprostaglandin-2alpha (8-iso-PGF2α), flow-mediated dilation (FMD) and reactive hyperaemia index (RHI) were evaluated before starting PCSK-9i treatment and after a 12-week treatment. Results: Twenty-five subjects were enrolled (52% males, mean age 51.5 years). At the 12-week assessment, we observed a 38% median reduction in TC, 52% in LDL-C, 7% in Lp(a) and 46% in LDL score. In parallel, 11-TXB2 and 8-iso-PGF2α showed a reduction of 18% and 17%, respectively. FMD changed from 4.78% ± 2.27 at baseline to 10.6% ± 5.89 at 12 weeks (p < 0.001), with RHI changing from 2.37 ± 1.23 to 3.76 ± 1.36 (p < 0.001). A multivariate analysis showed that, after adjusting for potential confounders, change in LDL score was an independent predictor of changes in FMD (β = −0.846, p = 0.015) and in 8-iso-PGF2α (β = 0.778, p = 0.012). Conclusions: Small dense LDL reduction (assessed by LDL score) is related to changes in oxidation markers and endothelial function in patients with FH treated with PCSK-9i.

Original languageEnglish
Pages (from-to)229-236
Number of pages8
JournalThrombosis Research
Volume194
DOIs
Publication statusPublished - Oct 2020

ASJC Scopus subject areas

  • Hematology

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