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Familial Hypercholesterolemia: Do HDL Play a Role?

Juan Pedro-Botet1,2,3, Elisenda Climent1,2,3, David Benaiges1,2,3

  • 1Endocrinology and Nutrition Department, Hospital del Mar, 08003 Barcelona, Spain.

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|August 6, 2021
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Summary

High cholesterol in heterozygous familial hypercholesterolemia (HeFH) significantly increases cardiovascular disease (CVD) risk. This review explores how abnormal high-density lipoprotein (HDL) function contributes to CVD in HeFH patients.

Keywords:
HDL functionalitycardiovascular diseaseepigeneticsfamilial hypercholesterolemiageneticshigh density lipoproteins

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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.