Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor therapy reduces the level of DNA damage in patients with heterozygous familial hypercholesterolemia

Heterozygous Familial Hypercholesterolaemia (HeFH) is a common autosomal dominant genetic disease (1:300) characterized by elevated LDL-C leading to premature atherosclerosis. Treatment with a PCSK9 inhibitor (iPCSK9) is recommended in high cardiovascular risk FH patients if the treatment goal is not achieved on maximal tolerated statin plus ezetimibe. The aim of this study was to examine the changes in DNA damage in HeFH patients associated with iPCSK9 use. Fifty-seven patients were included: a normolipidemic group (control; n=20) and patients with HeFH (study group; n=36). DNA damage was determined by alkaline comet assay. PCSK9 protein level was assessed by ELISA. The levels of Lp(a) in human serum were quantitatively turbidimetrically assay. PCSK9i treatment was associated with lower DNA damage, Lp(a), PCSK9 and lipid profile than before treatment. However, 20 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 moderately (r=0.48) correlates with reduced DNA damage. PCSK9i therapy reduces the level of DNA damage in HeFH patients, regardless of the type of inhibitor. The reduction in DNA damage is not related to the changes in lipid profile or Lp(a) induced by PCSK9i, but it is dependent on PCSK9 level.