Lipid-lowering therapy reduces oxidised-apoB immune complexes but not other oxidative markers in patients with Lp(a) 75 nmol/L or more (Clin Res Cardiol 2026)

Original title: Modulation of oxidation-related immune markers by lipid-lowering medications in individuals with elevated lipoprotein(a)

Clin Res Cardiol · 23 March 2026 · 4

Koutsogianni AD, Barkas F, Tellis C, Tselepis A, Liamis G, Tsimikas S, Liberopoulos E

Prospective study of 70 patients with Lp(a) 75 nmol/L or more, assigned to high-intensity statin monotherapy (n=28), statin plus ezetimibe (n=31), or statin plus ezetimibe plus a PCSK9 inhibitor (n=11), with oxidative and immune biomarkers measured at baseline and 3 months. Mean age was 51±15 years and 40% were male. IgG apoB-containing immune complexes fell significantly in all three groups (by 18.3%, 17.5% and 25.5% respectively, all p<0.05), but IgM immune complexes and IgG/IgM anti-MDA-mimotope autoantibodies did not change in any group. The clinical significance of reducing IgG immune complexes without affecting other oxidative markers remains to be established.

Original abstract

Background: Oxidative modification of apolipoprotein B-100 (apoB) containing particles and subsequent immune responses contribute to the pathogenesis of atherosclerosis. Circulating IgG and IgM apoB-containing immune complexes (apoB-IC) and autoantibodies to a malondialdehyde mimotope (anti-MDA-mimotope) serve as biomarkers of oxidative stress and immune activation in atherosclerotic cardiovascular disease. Elevated lipoprotein(a) [Lp(a)] is associated with increased oxidative burden and immune activation.

Purpose: To investigate the effect of lipid-lowering medications on IgG and IgM apoB-IC and IgG and IgM autoantibodies to an MDA-mimotope in individuals with elevated lipoprotein(a) [Lp(a)] concentrations.

Methods: In this prospective study, patients (n = 70) with Lp(a) levels ≥ 75 nmol/L were assigned to 3 treatment regimens according to current guidelines: high-intensity statin monotherapy (n = 28), ezetimibe added to high-intensity statin (n = 31) and proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) added to high-intensity statin plus ezetimibe (n = 11). IgG and IgM apoB-IC and IgG and IgM anti-MDA-mimotope were measured at baseline and 3 months after treatment initiation.

Results: Patients had a mean age of 51 ± 15 years and 40% were male. Significant reductions in IgG apoB-IC levels were observed following treatment with high-intensity statins, add-on ezetimibe and add-on PCSK9i (by 18.3%, 17.5% and 25.5%, respectively, all p < 0.05). No significant changes in IgM apoB-IC, or IgG and IgM anti-MDA-mimotope levels were observed in any treatment group.

Conclusions: In individuals with Lp(a) levels ≥ 75 nmol/L, high-intensity statins, add-on ezetimibe and add-on PCSK9i reduced IgG apoB-IC but did not affect IgM apoB-IC, or IgG and IgM anti-MDA-mimotope levels. The clinical significance of these findings warrants further investigation.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.