Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Steiner,L.
Effects of PCSK9-Antibodies on Cholesterol Metabolism
Humanmedizin; [Diplomarbeit] Medical University of Graz;2019. pp. 56
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Silbernagel Günther
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- Abstract:
- Proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies have been shown in the large-scaled FOURIER study and the ODYSSEY OUTCOMES study to reduce cardiovascular endpoints. It is not completely understood how PCSK9-antibodies affect cholesterol synthesis and absorption and circulating PCSK9 levels. Moreover, the implications of lipid-lowering pretreatment with statins and/or ezetimibe on treatment with PCSK9-antibodies are unclear. In an observational cross-sectional and longitudinal clinical trial 245 patients with hypercholesterolemia received PCSK9-antibodies. At the beginning of therapy with PCSK9-antibodies and 4 - 8 weeks after starting therapy with PCSK9-antibodies blood samples were taken. We measured the non-cholesterol sterols campesterol and sitosterol as markers of cholesterol absorption and lathosterol as a marker of cholesterol synthesis. 84 of the participants had no pretreatment, 26 with ezetimibe, 38 with statins and 97 with ezetimibe and statins. With intensified pretreatment circulating PCSK9 increased significantly. Therapy with PCSK9-antibodies resulted in an increase of circulating PCSK9 of 760 ± 45 %, a decrease of total cholesterol by -38.8 ± 0.9 %, a decrease of LDL-C by -52.1 ± 1.7 %, an increase of HDL-C by 13.8 ± 1.5 % and a decrease of total triglycerides by -17.1 ± 1.8 % (all p<0.001). Lathosterol was reduced by -30.4 ± 3.5 %, campesterol by -30.8 ± 3.1 % and sitosterol by -26.5 ± 3.0 % (all p<0.001). For the ratios of the non-cholesterol sterols to cholesterol no significant changes could be observed except for the sitosterol to cholesterol ratio with a modest increase (p=0.009). Considering the effects of PCSK9-antibody therapy on the different pretreatments, no significant differences between the pretreatments were found for all analysed parameters. There was a gradual increase in circulating PCSK9 with increased intensity of lipid lowering pretreatment like a counter-regulation, so that PCSK9-antibodies might have a strong effect in lowering cholesterol as an add on therapy by blocking this counter-regulation. We saw a significant decrease of the non-cholesterol sterols concentrations, but without significant changes in the balance between cholesterol synthesis and absorption. So we conclude, that PCSK9-antibodies doesn’t have a strong effect on cholesterol absorption or synthesis. The different pretreatments have no impact on the effect of PCSK9-antibodies. This also suggests that PCSK9-antibodies have no strong influence on lipid synthesis or absorption.