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Does elevated C-reactive protein increase atrial fibrillation risk? A Mendelian randomization of 47,000 individuals

Sarah C W Marott1, Børge G Nordestgaard, Jeppe Zacho

  • 1Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark.

Journal of the American College of Cardiology
|August 28, 2010
PubMed

Insights

Elevated C-reactive protein (CRP) levels are linked to a higher risk of atrial fibrillation. However, genetic factors influencing CRP do not appear to cause this increased risk, suggesting CRP itself may not be the direct cause.

Area of Science:

  • Cardiovascular Medicine
  • Inflammation Research
  • Genetics

Background:

  • Elevated C-reactive protein (CRP) levels have been previously associated with an increased risk of developing atrial fibrillation.
  • Investigating the nature of this association is crucial for understanding cardiovascular disease mechanisms.

Purpose of the Study:

  • To determine if the association between C-reactive protein (CRP) and atrial fibrillation risk is robust and potentially causal.
  • To differentiate between the effects of elevated plasma CRP and genetically influenced CRP levels on atrial fibrillation risk.

Main Methods:

  • Analysis of data from 10,276 individuals in the Copenhagen City Heart Study and 36,600 individuals in the Copenhagen General Population Study.
  • Measurement of high-sensitivity C-reactive protein (hs-CRP) levels and genotyping for four CRP gene polymorphisms.
  • Utilized logistic regression and instrumental variable analysis to assess the relationship between CRP levels and atrial fibrillation risk.

Main Results:

  • Higher C-reactive protein (CRP) levels were associated with a significantly increased risk of atrial fibrillation, even after adjustments for multiple factors.
  • Genetically determined variations in CRP levels did not correlate with an increased risk of atrial fibrillation.
  • Instrumental variable analysis suggested a weaker, non-significant causal effect of genetically elevated CRP on atrial fibrillation compared to observed associations with plasma CRP levels.

Conclusions:

  • While elevated plasma C-reactive protein (CRP) robustly associates with increased atrial fibrillation risk, genetically elevated CRP levels do not.
  • These findings suggest that elevated plasma CRP may not be a direct causal factor for atrial fibrillation, implying other inflammatory or related mechanisms might be involved.
Abstract

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