The effect of lipid-lowering treatment on indices of MASLD in familial hypercholesterolemia patients

Chrysoula Boutari; Christos V Rizos; George Liamis; Ioannis Skoumas; Loukianos Rallidis; Anastasia Garoufi; Genovefa Kolovou; George Sfikas; Konstantinos Tziomalos; Emmanouil Skalidis; Vasileios Kotsis; Michalis Doumas; Kimon Stamatelopoulos; Vaia Lambadiari; Panagiotis Anagnostis; Amalia Boufidou; Vasiliki Giannakopoulou; Georgia Anastasiou; Ermioni Petkou; Charalambos Vlachopoulos; Ioanna Dima; Georgios Fakas; Konstantinos A Papathanasiou; Achilleas Attilakos; Vana Kolovou; Charalambos Koumaras; Dimitrios Agapakis; Evangelos Zacharis; Christina Antza; Haralampos Milionis; Evangelos Liberopoulos; Christos S Mantzoros

doi:10.1016/j.clnu.2024.10.020

The effect of lipid-lowering treatment on indices of MASLD in familial hypercholesterolemia patients

Clin Nutr. 2024 Oct 16;43(12):84-91. doi: 10.1016/j.clnu.2024.10.020. Online ahead of print.

Authors

Chrysoula Boutari¹, Christos V Rizos², George Liamis², Ioannis Skoumas³, Loukianos Rallidis⁴, Anastasia Garoufi⁵, Genovefa Kolovou⁶, George Sfikas⁷, Konstantinos Tziomalos⁸, Emmanouil Skalidis⁹, Vasileios Kotsis¹⁰, Michalis Doumas¹¹, Kimon Stamatelopoulos¹², Vaia Lambadiari¹³, Panagiotis Anagnostis¹⁴, Amalia Boufidou¹⁵, Vasiliki Giannakopoulou¹⁶, Georgia Anastasiou¹⁷, Ermioni Petkou², Charalambos Vlachopoulos³, Ioanna Dima³, Georgios Fakas⁴, Konstantinos A Papathanasiou⁴, Achilleas Attilakos¹⁸, Vana Kolovou⁶, Charalambos Koumaras⁷, Dimitrios Agapakis⁸, Evangelos Zacharis⁹, Christina Antza¹⁰, Haralampos Milionis², Evangelos Liberopoulos¹⁹, Christos S Mantzoros²⁰

Affiliations

¹ Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration General Hospital, Thessaloniki, Greece; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
² Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece.
³ 1(st) Cardiology Department, Lipid Clinic, Athens Medical School, National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece.
⁴ Department of Cardiology, Medical School, National and Kapodistrian University of Athens, Attikon University General Hospital, Athens, Greece.
⁵ Second Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, General Children's Hospital "P. & A. Kyriakou", Athens, Greece.
⁶ Cardiometabolic Center, Lipid Clinic, LA Apheresis Unit, Metropolitan Hospital, Athens, Greece.
⁷ Department of Internal Medicine, 424 General Military Training Hospital, Thessaloniki, Greece.
⁸ 1(st) Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece.
⁹ Cardiology Clinic, University General Hospital of Heraklion, Heraklion, Greece.
¹⁰ 3(rd) Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Papageorgiou General Hospital, Thessaloniki, Greece.
¹¹ Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippokration General Hospital, Thessaloniki, Greece.
¹² Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
¹³ 2(nd) Propaedeutic Internal Medicine Department and Diabetes Research Unit, National and Kapodistrian University of Athens, Attikon University General Hospital, Athens, Greece.
¹⁴ Department of Endocrinology, Police Medical Center, Thessaloniki, Greece.
¹⁵ 1(st) Department of Cardiology, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece.
¹⁶ Cardiology Clinic, "Tzaneio" General Hospital, Piraeus, Greece.
¹⁷ Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Internal Medicine, Medical School, University of Ioannina, Ioannina, Greece.
¹⁸ Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, C' Pediatrics Clinic, Attikon University General Hospital, Athens, Greece.
¹⁹ 1(st) Propaedeutic Department of Medicine, School of Medicine, National and Kapodistrian University of Athens, Laiko Hospital, Athens, Greece.
²⁰ Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Medicine, Boston VA Healthcare System, Boston, MA, USA. Electronic address: cmantzor@bidmc.harvard.edu.

PMID: 39437569
DOI: 10.1016/j.clnu.2024.10.020

Abstract

Background & aims: The effect of lipid-lowering treatment (LLT) on metabolic dysfunction associated steatotic liver disease (MASLD) is unclear. This is relevant for patients with familial hypercholesterolemia (FH) who are on lifelong LLT. We aimed to evaluate the effect of LLT on MASLD indices in this population.

Methods: Patients with at least possible diagnosis of FH were included into the Hellenic FH Registry (HELLAS-FH) registry. We analyzed the effect of statin monotherapy, statin/ezetimibe and statin/ezetimibe/proprotein convertase subtilisin/kexin 9 inhibitors (PCSK9i) on MASLD indices, i.e., original triglyceride-glucose index (TyGO) and triglyceride-glucose index (TyG). We compared changes of TyG and TyGO before any treatment and after at least one year of stable LLT.

Results: We included 1289 patients: n = 569 in the statin monotherapy group (mean age = 51 ± 15 years, 52.7 % males), n = 629 in the statin/ezetimibe group (52 ± 14 years, 51.8 %), and n = 91 in the statin/ezetimibe/PCSK9i group (54 ± 13 years, 58.2 %). Compared with baseline, TyGO and TyG decreased significantly following statin monotherapy (8.61 vs 8.49 and 4.65 vs 4.59, respectively, both p < 0.01), statin/ezetimibe (8.59 vs 8.41 and 4.64 vs 4.55, respectively, both p < 0.01) and statin/ezetimibe/PCSK9i (8.79 vs 8.55 and 4.74 vs 4.62, respectively, both p < 0.01). There was no difference regarding the change of TyGO and TyG between groups after adjusting for baseline levels. A greater percentage of patients in the statin/ezetimibe and statin/ezetimibe/PCSK9i groups exhibited TyGO-defined MASLD resolution compared with statin monotherapy (p < 0.05). After adjustment for possible confounders, LLT was significantly associated with MASLD resolution.

Conclusions: MASLD indices were significantly improved in all LLT groups in FH patients. Statin/ezetimibe and statin/ezetimibe/PCSK9i were associated with greater TyGO-defined MASLD resolution compared with statin monotherapy.

Keywords: Familial hypercholesterolemia; Lipid-lowering treatment; Liver indices; MASLD.