Abstract：
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.
journal_name
Vascul Pharmacoljournal_title
Vascular pharmacologyauthors
Hollstein T,Vogt A,Grenkowitz T,Stojakovic T,März W,Laufs U,Bölükbasi B,Steinhagen-Thiessen E,Scharnagl H,Kassner Udoi
10.1016/j.vph.2019.03.002subject
Has Abstractpub_date
2019-05-01 00:00:00pages
8-15eissn
1537-1891issn
1879-3649pii
S1537-1891(18)30438-5journal_volume
116pub_type
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