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LCAT, HDL cholesterol and ischemic cardiovascular disease: a Mendelian randomization study of HDL cholesterol in

Christiane L Haase1, Anne Tybjærg-Hansen, Abbas Ali Qayyum

  • 1Department of Clinical Biochemistry, Rigshospitalet, The Copenhagen City Heart Study, University of Copenhagen, DK-2100 Copenhagen, Denmark.

The Journal of Clinical Endocrinology and Metabolism
|November 18, 2011
PubMed

Insights

High-density lipoprotein (HDL) cholesterol is linked to lower heart disease risk. However, genetically lowering HDL cholesterol did not increase myocardial infarction risk, suggesting low HDL may not directly cause heart attacks.

Area of Science:

  • Cardiovascular Medicine
  • Genetics
  • Epidemiology

Background:

  • High-density lipoprotein (HDL) cholesterol levels are epidemiologically associated with a reduced risk of ischemic cardiovascular disease.
  • The causal relationship between HDL cholesterol levels and ischemic cardiovascular disease remains unclear.

Purpose of the Study:

  • To investigate the causal relationship between high-density lipoprotein (HDL) cholesterol levels and the risk of myocardial infarction (MI).

Main Methods:

  • Utilized data from the Copenhagen City Heart Study (CCHS) and Copenhagen General Population Study (CGPS) involving over 60,000 participants.
  • Employed instrumental variable analysis using the S208T genetic variant (rs4986970) associated with HDL cholesterol levels.
  • Examined the association between genetically influenced HDL cholesterol reduction and the risk of MI.

Main Results:

  • Epidemiological analysis showed a 13% decrease in HDL cholesterol associated with an 18% increase in MI risk in the CCHS.
  • The S208T variant decreased HDL cholesterol by 13% but was not associated with an increased risk of MI or other ischemic events.
  • Instrumental variable analysis indicated no causal link between genetically decreased HDL cholesterol and increased MI risk.

Conclusions:

  • Low plasma HDL cholesterol levels are robustly associated with an increased risk of MI.
  • Genetically determined lower HDL cholesterol levels did not show an increased risk of MI.
  • These findings suggest that low HDL cholesterol levels may not be a direct cause of MI.
Abstract

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