Effect of add-on PCSK9 inhibitors on endocan and arterial stiffness in heterozygous familial hypercholesterolemia: a two-lipid center real-world study

Background and aims: Endothelial dysfunction (ED) represents an early key event in atherogenesis. Our aim was to evaluate the efficacy of six months add-on PCSK9 monoclonal antibodies (mAbs) on endothelial function assessed by endocan plasma levels and PWV in a cohort of HeFH subjects; furthermore, we investigated the association of endocan lowering and PWV variation. Methods and results: In this prospective observational study, we evaluated 30 FH subjects on high-intensity statins plus ezetimibe and with an off-target LDL-C. All patients received PCSK9 mAbs therapy and obtained biochemical analysis as well as endocan measurement and PWV evaluation at baseline and after six months of PCSK9 mAbs. After six months of add-on PCSK9 mAbs therapy, a significant reduction of TC, LDL-C, Non-HDL-C, TG, Lp(a) and ApoB was observed; moreover, both PWV and endocan significantly improved after six months of treatment. Finally, univariate linear regression analysis showed that ΔPWV was significantly associated with ΔEndocan (p value < 0.001). Conclusions: PCSK9 inhibition was associated with significant improved endocan levels and PWV in a cohort of HeFH subjects. ΔEndocan was significantly associated with ΔPWV. Our exploratory findings demonstrate endothelial benefits of PCSK9 mAbs in addition to LDL-C lowering and support endocan and PWV as complementary markers of vascular response in FH.