# Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitor Therapy Reduces the Level of DNA Damage in Patients with Heterozygous Familial Hypercholesterolemia

## TL;DR

This study shows that PCSK9 inhibitor therapy lowers DNA damage in patients with a genetic condition causing high cholesterol.

## Contribution

The study demonstrates a novel link between PCSK9 inhibition and reduced DNA damage in HeFH patients.

## Key findings

- PCSK9 inhibitor treatment reduced DNA damage, Lp(a), PCSK9, and lipid levels in HeFH patients.
- Reduced PCSK9 levels moderately correlated with reduced DNA damage (r = 0.48).
- Lp(a) reduction did not correlate with DNA damage reduction in treated patients.

## Abstract

Heterozygous familial hypercholesterolemia (HeFH) is a common autosomal dominant genetic disease (1:250) characterized by elevated LDL-C. Patients with HeFH are at increased risk of premature atherosclerosis and have at least a 10-fold greater chance of cardiovascular disease (CVD). The present study examines the effect of PCSK9 inhibitor treatment (iPCSK9: arilocumab or evolocumab) on DNA damage in HeFH patients. Fifty-six patients were studied, with a normolipidemic group (control; n = 20) and patients with HeFH (study group; n = 36). DNA damage was determined by alkaline comet assay and PCSK9 protein level by ELISA. PCSK9i treatment was found to be associated with lower DNA damage, Lp(a), PCSK9, and lipid profile compared to before treatment. However, 16 of 36 patients still had Lp(a) values above 125 nmol/L, and reduced Lp(a) did not correlate with reduced DNA damage. Reduced PCSK9 demonstrated a moderately positive correlation (r = 0.48) with reduced DNA damage. PCSK9i therapy reduces the level of DNA damage in HeFH patients, regardless of the type of inhibitor. While our findings confirm that PCSK9 treatment can reduce DNA damage, the mechanism remains unclear.