Background: Proprotein convertase subtilisin-kexin type 9 inhibitors (PCSK9-I) reduce low-density lipoprotein (LDL) cholesterol in human studies. Previous studies suggest that PCSK9-I may also affect very-low-density lipoproteins (VLDL). We therefore studied VLDL size and composition in a "real-world" study population with the use of β-quantification.
Subjects And Methods: 350 patients (62 ± 11 years old, 58% men, 22% with diabetes mellitus) with different concomitant lipid lowering therapies, and in whom PCSK9-I treatment was indicated, received either evolocumab (140 mg) or alirocumab (75 or 150 mg). The major lipoprotein fractions were separated by β-quantification and lipid and apolipoprotein compositions were determined before and 4 weeks after initiation of PCSK9-I treatment.
Results: After 4 weeks of PCSK9-I treatment, the ratio of triglycerides to apolipoprotein B in VLDL particles (VLDL-TG/apoB ratio) increased by 40% (p < .0001). VLDL-associated apolipoproteins E, CII, and CIII were reduced by 29.4%, 16.4%, and 12.4%, respectively (all p < .0001).
Conclusion: PCSK9-I treatment increased VLDL size (estimated by an increased VLDL-TG/apoB ratio) and reduced VLDL-associated apolipoproteins in a heterogeneous "real-world" study-population, reflecting a higher clearance of small atherogenic VLDL remnant particles by PCSK9-I. This may potentially lower cardiovascular risk in clinical routine patients beyond low-density cholesterol (LDL-C) reduction.
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http://dx.doi.org/10.1016/j.vph.2019.03.002 | DOI Listing |
Rev Cardiovasc Med
November 2024
Department of Cardiovascular Diseases, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Lipoprotein a (Lp(a)) is a lipid biomarker that binds cholesterol and bears independent cardiovascular risk. Strategies to lower the level of Lp(a) and mitigate such risk are important both for primary and secondary prevention. Currently there are no approved therapies targeting Lp(a) directly.
View Article and Find Full Text PDFPLoS One
August 2024
Cardiovascular Center, Territorial Specialistic Department, University Hospital and Health Services of Trieste, Trieste, Italy.
Int J Mol Sci
October 2023
Division of Cardiology, Department of Advanced Biomedical Sciences, University of Naples Federico II, 80131 Naples, Italy.
Int J Mol Sci
July 2023
Division of Cardiology, Department of Advanced Biomedical Sciences, University of Naples Federico II, 80134 Naples, Italy.
This review aims to examine the complex interaction between dyslipidemia, platelet function, and related drug treatments. In particular, the manuscript provides an overview of the effects of major hypolipidemic drugs on platelet function. Indeed, growing evidence supports the view that statins, ezetimibe, PCSK9 inhibitors, inclisiran, and icosapent ethyl also act as antithrombotics.
View Article and Find Full Text PDFGenes (Basel)
March 2023
Department of Pediatrics, Amsterdam Cardiovascular Sciences, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Center, Location AMC, 1105 AZ Amsterdam, The Netherlands.
Familial hypercholesterolemia (FH) is a hereditary disorder that causes severely elevated low-density lipoprotein (LDL-C) levels, which leads to an increased risk for premature cardiovascular disease. A variety of genetic variants can cause FH, namely variants in the genes for the LDL receptor (), apolipoprotein B (), proprotein convertase subtilisin/kexin type 9 (), and/or LDL-receptor adaptor protein 1 (). Variants can exist in a heterozygous form (HeFH) or the more severe homozygous form (HoFH).
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