The relationship between genotype of familial hypercholesterolemia and the efficacy of PCSK9 inhibitors / 中华心血管病杂志
Chinese Journal of Cardiology
; (12): 572-579, 2021.
Article
en Zh
| WPRIM
| ID: wpr-941320
Biblioteca responsable:
WPRO
ABSTRACT
Objective:
This study intends to explore the difference in the efficacy of PCSK9 inhibitors in patients with different FH phenotypes by analyzing the level of blood lipids before and after treatment with PCSK9 inhibitors in patients with familial hypercholesterolemia (FH) with different allele grades.Methods:
Patients with FH phenotype, who admitted to Beijing Anzhen Hospital from January 2019 to October 2020, were enrolled. Age, sex and other clinical information were collected from enrolled, and the pathogenic genes were detected by the second generation sequencing technique. The patients were divided into five groups according to the number of alleles involved and the degree of gene damage single allele-null mutation group, single allele-defect mutation group, multi-allele-null mutation group, multi-allele-defect mutation group and no major pathogenic gene mutation group. The results of blood lipids were collected before medication, 4-6 weeks of intensive statin treatment and one month after combined treatment with PCSK9 inhibitor (PCSK9i). The LDL-C level were compared among groups. ASCVD risk stratification was performed in all patients, and the proportion of LDL-C level reaching the corresponding risk stratification target value of each genotype group after treatment was analyzed.Results:
A total of 66 patients with FH phenotype were included, including 47 males (71.2%) and 19 females (28.8%),the mean age was(43.1±13.4 years). There were 7 cases in single allele-null mutation group (10.6%), 25 cases in single allele-defect mutation group (37.9%), 8 cases in multi-allele-null mutation group (12.1%), 18 cases in multi-allele-defect mutation group (27.3%) and 8 cases in no major pathogenic mutation group (12.1%). The degree of LDL-C reduction post combined PCSK9 inhibitor therapy was as follows single allele mutation group>no major pathogenic mutation group>multi-allele mutation group, general distribution was in the range of 0-90.0%. Two groups of single allele mutation and no major pathogenic mutation group>50.0%>multi-allele mutation group. Under the combined treatment of PCSK9 inhibitors, the further decrease of LDL-C was in the order of single allele mutation group>non-major pathogenic mutant group>multi-allele mutation group. The efficacy of combined therapy on reducing LDL-C at 1 month after treatment decreased with the increase of baseline LDL-C level (r = 0.46, P<0.001) in patients with FH phenotype. In addition, the further decrease of LDL-C level post high-intensity statin therapy combined with PCSK9 inhibitors decreased with the increase of baseline LDL-C levels (r = 0.40, P<0.001). The degree of LDL-C decrease was high and stable by statin combined with PCSK9 inhibitor therapy in single allele mutation group. In the single allele-defect mutant group, the decrease of LDL-C increased with the increase of baseline LDL-C level post intensive statin treatment and combined PCSK9 inhibitor treatment ((r=0.54, P=0.009); r=0.45,P=0.030), and the further decrease of LDL-C level decreased with the increase of baseline LDL-C level in single allele-defect mutant group post combined therapy with PCSK9 inhibitor (r=0.43, P=0.040). The decrease of LDL-C in patients with the multi-allele mutation group varied with different pathogenic gene loci and combinations post combined therapy with PCSK9 inhibitor. There was no significant difference in the level of blood lipids between the group without major pathogenic gene mutation and the group with single allele mutation before and after treatment. The percentage of patients achieving LDL-C goals with different genotypes of phenotypic FH were as follows single allele mutation group (86.7%), non-major pathogenic mutant group (75.0%) and multi-allele mutation grou (<5.0%).Conclusions:
All patients with different FH phenotypes could benefit from the intensive lipid-lowering therapy with statins and PCSK9 inhibitors, however, there are significant differences in the efficacy of lowering LDL-C in Chinese patients with FH phenotype with different molecular etiologies. Therefore, the pathogenic gene analysis may suggest the lipid-lowering effect of PCSK9 inhibitors in patients with FH.
Texto completo:
1
Base de datos:
WPRIM
Asunto principal:
Inhibidores de Hidroximetilglutaril-CoA Reductasas
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Proproteína Convertasa 9
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Genotipo
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Hiperlipoproteinemia Tipo II
Límite:
Adult
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Female
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Humans
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Male
Idioma:
Zh
Revista:
Chinese Journal of Cardiology
Año:
2021
Tipo del documento:
Article