Influence of the LDL-Receptor Genotype on Statin Response in Heterozygous Familial Hypercholesterolemia: Insights From the Canadian FH Registry.
Can J Cardiol
; 38(3): 311-319, 2022 03.
Article
em En
| MEDLINE
| ID: mdl-34774719
ABSTRACT
BACKGROUND:
Whether low-density lipoprotein (LDL) receptor (LDLR) residual activity influences the LDL-lowering effect of statins in heterozygous familial hypercholesterolemia (HeFH) remains unclear. The objective of this study was to investigate the relationship between the LDLR genotype and statin-induced LDL cholesterol (LDL-C) reductions in HeFH.METHODS:
A total of 615 individuals with HeFH (receptor-defective [RD] genotype n = 226; receptor-negative [RN] genotype n = 389) from 7 lipid clinics across Canada who initiated statin monotherapy were included in this retrospective longitudinal study. Statin-induced reductions in LDL-C among individuals with RD and RN genotypes were compared with the use of linear models.RESULTS:
There were 334 women and 281 men with a mean untreated LDL-C concentrations of 6.97 ± 1.65 mmol/L. Untreated and on-statin LDL-C levels where higher among patients with an RN genotype untreated RN 7.24 (95% confidence interval [CI] 6.98-7.50) mmol/L vs RD 6.70 (95% CI 6.41-6.98) mmol/L (P = 0.0002); on-statin RN 4.50 (95% CI 4.31-4.70) vs RD 4.05 (95% CI 3.84-4.26) mmol/L (P = 0.0004). After adjustments for age, sex, smoking status, untreated LDL-C concentrations, statin type and dose, as well as the clinic where the patients were treated, the LDL-C-lowering effect of statins was significantly weaker for individuals with an RN mutation than for individuals with an RD mutation RN -31.1% (95% CI -34.7% to -27.4) vs RD -36.5% (95% CI -40.4% to -32.6%); P < 0.0001. The LDLR genotype was the strongest nonmodifiable independent correlate of statin-induced LDL-C reductions (R2 = 2.3%; P = 0.0001).CONCLUSION:
The LDLR genotype is significantly associated with statin-induced reductions in LDL-C concentrations in HeFH.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Receptores de LDL
/
Inibidores de Hidroximetilglutaril-CoA Redutases
/
Metabolismo dos Lipídeos
/
Hiperlipoproteinemia Tipo II
/
LDL-Colesterol
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
/
Male
/
Middle aged
País/Região como assunto:
America do norte
Idioma:
En
Revista:
Can J Cardiol
Assunto da revista:
CARDIOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Canadá