Familial Hypercholesterolemia: Do HDL Play a Role?

Area of Science:

• Lipid metabolism
• Cardiovascular genetics
• Monogenic disorders

Background:

• Cardiovascular disease (CVD) is a major concern in heterozygous familial hypercholesterolemia (HeFH), a common inherited metabolic disorder.
• While high low-density lipoprotein (LDL) cholesterol is a primary driver, varying CVD rates suggest other factors are involved.
• Alterations in high-density lipoprotein (HDL) phenotype and function are observed in HeFH, potentially exacerbating CVD.

Purpose of the Study:

• To review quantitative and qualitative abnormalities of HDL particles in HeFH patients.
• To explore the role of HDL dysfunction in the high cardiovascular risk associated with HeFH.
• To examine the metabolic, genetic, and epigenetic factors influencing HDL in HeFH.

Main Methods:

• Narrative review of existing literature.
• Analysis of studies focusing on HDL characteristics in HeFH.
• Synthesis of information on metabolic, genetic, and epigenetic influences on HDL.

Main Results:

• HDL particles in HeFH patients exhibit both quantitative and qualitative abnormalities.
• These HDL alterations contribute to the presence and severity of CVD in the HeFH population.
• HDL's protective functions, including reverse cholesterol transport and antioxidant properties, may be impaired in HeFH.

Conclusions:

• Abnormalities in HDL are significant contributors to cardiovascular risk in HeFH beyond LDL cholesterol levels.
• Understanding these HDL defects is crucial for developing targeted therapies for HeFH patients.
• Further research into the metabolic, genetic, and epigenetic underpinnings of HDL dysfunction in HeFH is warranted.