Rethinking HDL-C: An In-Depth Narrative Review of Its Role in Cardiovascular Health

Prinka Perswani1, Syed Muhammad Ismail2, Hassan Mumtaz3

  • 1University of California, Riverside.

PubMed

Insights

Higher High-Density Lipoprotein Cholesterol (HDL-C) isn't always better for heart health. Genetic factors and extremely high HDL-C levels may unexpectedly increase cardiovascular disease (CVD) risk.

Area of Science:

  • Cardiovascular Science
  • Lipid Metabolism
  • Genetics

Background:

  • High-Density Lipoprotein Cholesterol (HDL-C) is a key biomarker for cardiovascular disease (CVD) risk.
  • Traditionally, higher HDL-C levels were considered protective against CVD.
  • Recent findings suggest a more complex, non-linear relationship between HDL-C and cardiovascular outcomes.

Purpose of the Study:

  • To explore the complex relationship between HDL-C levels and cardiovascular outcomes.
  • To investigate the impact of genetic factors on HDL-C levels and associated CVD risk.
  • To challenge the conventional view that elevated HDL-C is universally beneficial.

Main Methods:

  • Review of current research on HDL-C, cardiovascular disease, and genetics.
  • Analysis of studies investigating associations between genetic determinants of HDL-C and CVD susceptibility.
  • Examination of emerging evidence on risks linked to ultra-high HDL-C levels.

Main Results:

  • Extremely high HDL-C levels, particularly those linked to genetic factors, may be associated with increased CVD risk.
  • The protective effect of HDL-C is not absolute and can be influenced by particle functionality and composition.
  • Low HDL-C remains a significant risk factor, but the role of very high HDL-C is nuanced.

Conclusions:

  • The association between HDL-C and cardiovascular outcomes is multifactorial and influenced by genetics.
  • Elevated HDL-C does not always confer protection and may, in some cases, increase CVD risk.
  • Further research is crucial to understand the intricate mechanisms and implications for CVD risk assessment and treatment.

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