1. The roles of apo(a) size, phenotype, and dominance pattern in PCSK9-inhibition-induced reduction in Lp(a) with alirocumab[S]
- Author
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Enkhmaa, Byambaa, Anuurad, Erdembileg, Zhang, Wei, Yue, Kun, Li, Ching-Shang, and Berglund, Lars
- Subjects
Biological Sciences ,Biomedical and Clinical Sciences ,Clinical Sciences ,Atherosclerosis ,Cardiovascular ,Genetics ,Antibodies ,Monoclonal ,Antibodies ,Monoclonal ,Humanized ,Apoprotein(a) ,Gene Expression Regulation ,Humans ,PCSK9 Inhibitors ,Phenotype ,Protease Inhibitors ,Protein Isoforms ,lipoprotein ,apolipoprotein ,apolipoproteins ,clinical studies ,lipoproteins ,drug therapy/hypolipidemic drugs ,familial hypercholesterolemia ,hypercholesterolemic ,monoclonal antibody ,low density lipoprotein cholesterol reduction ,genetic variability ,proprotein convertase subtilisin/kexin type 9 ,Biochemistry and Cell Biology ,Medical Biochemistry and Metabolomics ,Biochemistry & Molecular Biology ,Biochemistry and cell biology ,Medical biochemistry and metabolomics - Abstract
An elevated level of lipoprotein (a) [Lp(a)] is a risk factor for CVD. Alirocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9, is reported to reduce Lp(a) levels. The relationship of Lp(a) reduction with apo(a) size polymorphism, phenotype, and dominance pattern and LDL cholesterol (LDL-C) reduction was evaluated in a pooled analysis of 155 hypercholesterolemic patients (75 with heterozygous familial hypercholesterolemia) from two clinical trials. Alirocumab significantly reduced total Lp(a) (pooled median: -21%, P = 0.0001) and allele-specific apo(a), an Lp(a) level carried by the smaller (median: -18%, P = 0.002) or the larger (median: -37%, P = 0.0005) apo(a) isoform, at week 8 versus baseline. The percent reduction in Lp(a) level with alirocumab was similar across apo(a) phenotypes (single vs. double bands) and carriers and noncarriers of a small size apo(a) (≤22 kringles). The percent reduction in LDL-C correlated significantly with the percent reduction in Lp(a) level (r = 0.407, P < 0.0001) and allele-specific apo(a) level associated with the smaller (r = 0.390, P < 0.0001) or larger (r = 0.270, P = 0.0183) apo(a) sizes. In conclusion, alirocumab-induced Lp(a) reduction was independent of apo(a) phenotypes and the presence or absence of a small size apo(a).
- Published
- 2017