Autor:innen:
J. Schremmer (Düsseldorf, DE)
L. Busch (Düsseldorf, DE)
S. Baasen (Düsseldorf, DE)
H. Yvonne (Düsseldorf, DE)
R. Sansone (Düsseldorf, DE)
M. Kelm (Düsseldorf, DE)
M. Stern (Düsseldorf, DE)
Background: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) effectively decrease low-density lipoprotein cholesterol (LDL-C) and reduce cardiovascular events in patients with hypercholesterolemia. Recent studies suggest a partially LDL-C independent beneficial effect of PCSK9 inhibitor therapy on endothelial function and arterial stiffness, whereas nothing is yet known about the effect on peripheral microcirculation.
Objective: We aim to investigate favorable effects of PCSK9i therapy on vascular parameters beyond its lipid lowering effect.
Methods: In this prospective observational trial, 32 patients (mean age 61 +/- 13 years, mean baseline LDL-C 141 +/- 54 mg/dl, 53% female, 91% with coronary artery disease) with hypercholesterolemia and indication for PCSK9i therapy were included. The majority (72%) was already under treatment with a statin or ezetimibe or the combination of both. Arterial stiffness was measured as pulse wave velocity (PWV) and augmentation index (AIx). Endothelial function was assessed as flow-mediated dilation (FMD) of the brachial artery using ultrasound. Peripheral tissue oxygenation (StO2) as a marker of microcirculation was assessed at the distal extremities (hand/feet) using near-infrared spectroscopy (NIRS) camera. Measurements were performed at baseline before the first PCSK9i injection and at six month follow up.
Results: After six months of PCSK9 inhibitor therapy, mean LDL-C levels decreased from 141,1 +/- 54,2 mg/dl [SD] to 59,6 +/- 29,92 mg/dl [SD] (p < 0,001, -56%), FMD significantly increased from 5,41 +/- 1,72 % [SD] to 6,4 +/- 1,9 % [SD] (p < 0,001, +19,4%), PWV decreased from 8,69 +/- 2,21 m/s [SD] to 8,27 +/- 1,66 m/s [SD] (p = 0,14, -5 %), AIx significantly decreased from 27,11 +/- 10,38 % [SD] to 23 +/- 9,68 % [SD] (p < 0,001, -16%), peripheral tissue oxygenation significantly increased from 66,89 +/- 12,35 % [SD] to 70,7 +/- 11,14 % [SD] (p = 0,012, +7%). There was no correlation between LDL-C reduction and changes in vascular parameters. Patients with statin background therapy showed greater improvements in vascular parameters than patients without background therapy.
Conclusions: PCSK9i therapy ameliorates arterial stiffness, endothelial function and peripheral microcirculation independently from its lipid lowering effect.