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U-shaped relationship between apolipoprotein A1 levels and mortality risk in men and women

Christian C Faaborg-Andersen1,2, Chang Liu2,3, Veerappan Subramaniyam4

  • 1Department of Internal Medicine, Massachusetts General Hospital, Boston, MA, USA.

European Journal of Preventive Cardiology
|November 9, 2022
PubMed

Insights

Both very low and very high levels of Apolipoprotein A1 (ApoA1) are linked to increased cardiovascular and all-cause mortality, indicating a U-shaped risk relationship in a large UK Biobank study.

Area of Science:

  • Cardiovascular Science
  • Genetics
  • Biochemistry

Background:

  • Apolipoprotein A1 (ApoA1) is the primary protein in high-density lipoprotein (HDL).
  • Low HDL cholesterol (HDL-C) is a known cardiovascular risk factor.
  • Recent research suggests very high HDL-C levels may also increase mortality risk.

Purpose of the Study:

  • To examine the sex-specific association between elevated ApoA1 levels and adverse health outcomes.
  • To investigate the genetic underpinnings of these associations.
  • To clarify the relationship between ApoA1, HDL-C, and mortality risk.

Main Methods:

  • Prospective cohort study utilizing the UK Biobank.
  • Analysis of serum ApoA1 levels as the primary exposure.
  • Tracking cardiovascular and all-cause mortality as primary and secondary outcomes.

Main Results:

  • A U-shaped relationship was observed between ApoA1 levels and mortality in 402,783 participants over 12.1 years.
  • The highest ApoA1 decile showed increased cardiovascular and all-cause mortality compared to the lowest risk decile.
  • This U-shaped pattern was present in both sexes, more pronounced in men, and not fully explained by genetics or alcohol intake.

Conclusions:

  • Both very low and very high ApoA1 levels are associated with increased cardiovascular and all-cause mortality.
  • The findings highlight a complex, non-linear relationship between ApoA1 and mortality risk.
  • Further research is needed to understand the mechanisms driving this U-shaped association.
Abstract

Keywords:
Apolipoprotein A1Coronary artery diseaseHigh-density lipoprotein cholesterolRisk factorsUK Biobank

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