1. The roles of apo(a) size, phenotype, and dominance pattern in PCSK9-inhibition-induced reduction in Lp(a) with alirocumab[S]
- Author
-
Lars Berglund, Wei Zhang, Erdembileg Anuurad, Byambaa Enkhmaa, Ching-Shang Li, and Kun Yue
- Subjects
medicine.medical_specialty ,Familial hypercholesterolemia ,QD415-436 ,030204 cardiovascular system & hematology ,Antibodies, Monoclonal, Humanized ,Apoprotein(a) ,Biochemistry ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Internal medicine ,medicine ,Humans ,Protein Isoforms ,Protease Inhibitors ,030212 general & internal medicine ,clinical studies ,Research Articles ,Dominance (genetics) ,Alirocumab ,biology ,PCSK9 ,lipoprotein (a) ,PCSK9 Inhibitors ,Antibodies, Monoclonal ,drug therapy/hypolipidemic drugs ,Cell Biology ,Lipoprotein(a) ,apolipoprotein (a) ,medicine.disease ,Proprotein convertase ,lipoproteins ,Phenotype ,Gene Expression Regulation ,biology.protein ,Kexin ,lipids (amino acids, peptides, and proteins) ,apolipoproteins ,Lipoprotein - 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