Medizinische Universität Graz - Research portal
Selected Publication:
Metzner, T.
Effects of Lipid-Therapy Intensification on Endothelial Function, Carotid Arteries, Lipoprotein Particle Subfractions, Inflammation and Post-Prandial Lipemia
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Medizinische Universität Graz; 2022. pp. 117
[OPEN ACCESS]
FullText
- Authors Med Uni Graz:
- Advisor:
- Scharnagl Hubert
- Silbernagel Günther
- Toplak Hermann
- Altmetrics:
- Abstract:
- Abstract in English Aims: The effects of alirocumab on vascular structure and function have been sparsely evaluated. Besides, non-invasive reliable imaging techniques are needed to evaluate pathological changes caused by atherosclerosis. To address these issues, we conducted ultrasound-based and magnetic resonance-based imaging assessments. Methods: All 24 recruited patients had an indication for PCSK9-antibody treatment. The treatment duration with alirocumab was 10 weeks. Outcome measures involved the change of fractional anisotropy of the carotid artery as a marker for vascular integrity, change of flow-dependent dilatation of the brachial artery as parameter for vascular function, change in the lipoprotein particle profile as well as the change of systemic inflammation or vascular biomarkers. Results: Among all recruited patients, 21 trial participants had a baseline and a week 10 visit as planned. Two patients injected alirocumab only twice, thus 19 participants completed the trial per protocol. Their mean LDL-cholesterol concentration was significantly reduced by alirocumab (p < 0.001). The particle concentrations of total and small-dense LDL also significantly decreased (p < 0.001), whereas the HDL particle concentration significantly increased (p = 0.001). Flow-dependent dilatation nominally increased by 41% but this was not statistically significant. Fractional anisotropy of the carotid artery did not change. Total plasma PCSK9 increased more than 3-fold in all 19 adherent patients (p < 0.001) but did not change in those two non-adherent patients with two injections of alirocumab only. Changes of plasma biomarkers regarding systemic inflammation or vascular function were not detectable. Conclusion: Statistically significant effects of alirocumab on vascular function or structure could not be shown in our exploratory pilot trial. More research efforts are needed to investigate the potential role of the novel magnetic resonance imaging technique in the clinical research setting. The assessment of total circulating PCSK9 concentration may be useful to distinguish non-adherent from non-responder patients. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT03559. Published: (Metzner et al., 2022a, Metzner et al., 2022b).