Impact of baseline LDL-C and Lp(a) levels on PCSK9-targeting therapy efficacy in subjects with familial hypercholesterolemia: real-world data from a tertiary lipid center.

Authors

Giosiana Bosco, Francesco Di Giacomo Barbagallo, Maurizio Di Marco, Sabrina Scilletta, Nicoletta Miano, Giovanni Pennisi, Alessandra Scamporrino, Ernestina Marianna De Francesco, Roberta Malaguarnera, Antonino Di Pino, Salvatore Piro, Roberto Scicali

Published in

Nutrition, metabolism, and cardiovascular diseases : NMCD. Pages 105035. Oct 15, 2026. Epub Oct 15, 2026.

Abstract

Familial hypercholesterolemia (FH) is characterized by elevated LDL-C and increased risk of premature cardiovascular events. PCSK9-targeting therapies reduce LDL-C and Lp(a), with evidence suggesting favorable vascular effects. This study aimed to evaluate the impact of baseline lipid levels on lipid reduction and mechanical vascular improvement after six months of PCSK9-targeting therapies and the association between baseline LDL-C and Lp(a) concentrations and ΔPWV in FH subjects.
We evaluated lipid profile and PWV at baseline and after six months of PCSK9-targeting therapies in 369 genetically confirmed FH subjects. Study population was divided into four groups based on the combination of baseline LDL-C and Lp(a) values dichotomized at their respective medians. After six months of PCSK9-targeting therapies, greater reductions in LDL-C and Lp(a) were observed in subjects with higher-than-median baseline lipid levels, along with progressive PWV improvement across groups; moreover, logistic regression showed that subjects with concomitantly higher-than-median baseline LDL-C and Lp(a) had the strongest association with ΔPWV (OR: 9.71; 95% CI: 3.14 - 17.85).
FH subjects with higher-than-median baseline LDL-C and Lp(a) showed greater lipid lowering and greater improvements in arterial stiffness after six months add-on PCSK9-targeting therapies; furthermore, higher-than-median baseline LDL-C and Lp(a) had the strongest association with PWV improvement.

PMID:
42957476
Bibliographic data and abstract were imported from PubMed on 30 Oct 2026.

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