Introduction
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Introduction
Familial Hypercholesterolemia (FH)
Familial Hypercholesterolemia (FH)
Clinical Manifestations of FH
FH: very high cholesterol exposure
FH - Clinical Diagnosis
FH - Clinical Diagnosis
Mutation Diagnosis of Heterozygous FH
Molecular Bases of FH
Molecular Bases of FH
Estimated % Diagnosed FH
HoFH is Caused by Mutations
Molecular Causes of FH
FH Is Most Frequently Caused by LDLR
Molecular Causes of FH
Molecular Causes of FH (cont.)
Molecular Causes of FH (cont.)
What Is the Frequency of Mutations
Heterozygous and Homozygous FH
Broad Spectrum of LDL-C levels in FH
Effect of Niacin on Plasma
Penn HoFH Cohort
LDL-C Levels Correlate With Residual LDLR
Common Genetic Variants
LDL-C Burden in Individuals With/Without FH
Molecular Bases of FH and Drug Target
LDLR Synthesis
LDLR and Cholesterol Synthesis
Statins Up-Regulate the LDLR
Statins Up-Regulate the LDLR
Most Lipid Lowering Drugs Affect LDL
PCSK9 Inhibition Prevents Degradation
PCSK9 Inhibition Prevents Degradation (cont.)
PCSK9 Levels Are Elevated in FH
PCSK9 Inhibition Lower LDL-C
Novel Lipid Lowering Drugs Affect LDL
Novel Lipid Lowering Drugs Affect LDL (cont.)
Mipomersen Lowers LDL-C in FH
Lomitapide Lowers LDL-C in HoFH
Summary
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