Search

Background: PCSK9 antibodies strongly reduce LDL cholesterol. The effects of PCSK9 antibodies on triglyceride metabolism are less pronounced. The present study aimed to investigate in detail the effects of alirocumab on triglycerides, triglyceride-rich lipoproteins, and lipase regulators., Methods: A total of 24 patients with an indication for treatment with PCSK9 antibodies were recruited. There were two visits at the study site: the first before initiation of treatment with alirocumab and the second after 10 weeks of treatment. Fat-tolerance tests, nuclear magnetic resonance spectroscopy, and enzyme-linked immunosorbent assays were performed to analyze lipid metabolism., Results: A total of 21 participants underwent the first and second investigation. Among these, two participants only received alirocumab twice and 19 patients completed the trial per protocol. All of them had atherosclerotic vascular disease. There was no significant effect of alirocumab treatment on fasting triglycerides, post-prandial triglycerides, or lipoprotein-lipase regulating proteins. Total, large, and small LDL particle concentrations decreased, while the HDL particle concentration increased (all p < 0.001). Mean total circulating PCSK9 markedly increased in response to alirocumab treatment ( p < 0.001). Whereas PCSK9 increased more than three-fold in all 19 compliant patients, it remained unchanged in those two patients with two injections only., Conclusion: Significant effects of alirocumab on triglyceride metabolism were not detectable in the ALIROCKS trial. The total circulating PCSK9 concentration might be a useful biomarker to differentiate non-adherence from non-response to PCSK9 antibodies.

Background: Short-term effects of alirocumab on vascular function have hardly been investigated. Moreover, there is a scarce of reliable non-invasive methods to evaluate atherosclerotic changes of the vasculature. The ALIROCKS trial was performed to address these issues using standard ultrasound-based procedures and a completely novel magnetic resonance-based imaging technique., Methods: A total of 24 patients with an indication for treatment with PCSK9 antibodies were recruited. There were 2 visits to the study site, the first before initiation of treatment with alirocumab and the second after 10 weeks of treatment. The key outcome measures included the change of carotid vessel wall fractional anisotropy, a novel magnetic resonance-based measure of vascular integrity, and the changes of carotid intima-media thickness and flow-dependent dilatation of the brachial artery measured with ultrasound., Results: A total of 19 patients completed the trial, 2 patients stopped treatment, 3 patients did not undergo the second visit due to the COVID pandemic. All of them had atherosclerotic vascular disease. Their mean (standard deviation) LDL-cholesterol concentration was 154 (85) mg/dL at baseline and was reduced by 76 (44) mg/dL in response to alirocumab treatment ( p < 0.001, n = 19). P-selectin and vascular endothelial growth factors remained unchanged. Flow-dependent dilatation of the brachial artery (+41%, p = 0.241, n = 18), carotid intima-media thickness ( p = 0.914, n = 18), and fractional anisotropy of the carotid artery ( p = 0.358, n = 13) also did not significantly change., Conclusion: Despite a nominal amelioration for flow-dependent dilatation, significant effects of short-term treatment with alirocumab on vascular function were not detectable. More work would be needed to evaluate, whether fractional anisotropy may be useful in clinical atherosclerosis research.

Orlistat is a lipase inhibitor that is applied for treating obesity. Lipases are required for digestion and absorption of dietary lipids and fat-soluble vitamins and carotenoids. The aim of this study was to compare the effects of orlistat therapy on plasma concentrations of oxygenated (beta-cryptoxanthin, lutein/zeaxanthin) and hydrocarbon (alpha-, beta-carotene, lycopene) carotenoids. Six patients with a body mass index (BMI) > or = 30 kg/m2 received 360 mg/d orlistat over 4.5 mon. Plasma carotenoid concentrations were determined at baseline (T0) and after 3 (T3) and 4.5 mon (T4.5) along with anthropometric, dietary, and biochemical indices, including plasma lipids, retinol, (alpha- and gamma-tocopherols, and FA. Baseline BMI was 32.7 +/- 1.97 kg/m2. Five of six patients lost weight; the average weight loss was 3.6 +/- 2.4% (P = 0.47). There were no significant changes in dietary carotenoid intakes. In contrast, plasma alpha- and beta-carotene concentrations decreased significantly from T0 to T4.5 by 45% (P = 0.006) and 32% (P = 0.013), respectively. Plasma lycopene decreased from T0 to T3 but increased again from T3 to T4.5, while beta-cryptoxanthin and lutein/zeaxanthin concentrations did not change. There were no significant alterations in tocopherol, retinol, and FA concentrations. In conclusion, even though weight loss was not significant, orlistat therapy was associated with significant decreases in plasma concentrations of the highly lipophilic hydrocarbon carotenoids, alpha- and beta-carotene.