Document Detail


Does elevated C-reactive protein increase atrial fibrillation risk? A Mendelian randomization of 47,000 individuals from the general population.
MedLine Citation:
PMID:  20797493     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: The purpose of this study was to test whether the association of C-reactive protein (CRP) with increased risk of atrial fibrillation is a robust and perhaps even causal association. BACKGROUND: Elevated levels of CRP previously have been associated with increased risk of atrial fibrillation. METHODS: We studied 10,276 individuals from the prospective Copenhagen City Heart Study, including 771 individuals who had atrial fibrillation during follow-up, and another 36,600 persons from the cross-sectional Copenhagen General Population Study, including 1,340 cases with atrial fibrillation. Individuals were genotyped for 4 CRP gene polymorphisms and had high-sensitivity CRP levels measured. RESULTS: A CRP level in the upper versus lower quintile associated with a 2.19-fold (95% confidence interval [CI]: 1.54- to 3.10-fold) increased risk of atrial fibrillation. Risk estimates attenuated slightly after multifactorial adjustment to 1.77 (95% CI: 1.22 to 2.55), and after additional adjustment for heart failure and plasma fibrinogen level to 1.47 (95% CI: 1.02 to 2.13) and 1.63 (95% CI: 1.21 to 2.20), respectively. Genotype combinations of the 4 CRP polymorphisms associated with up to a 63% increase in plasma CRP levels (p < 0.001), but not with increased risk of atrial fibrillation. The estimated causal odds ratio for atrial fibrillation by instrumental variable analysis for a doubling in genetically elevated CRP levels was lower than the odds ratio for atrial fibrillation observed for a doubling in plasma CRP on logistic regression (0.94 [95% CI: 0.70 to 1.27] vs. 1.36 [95% CI: 1.30 to 1.44]; p < 0.001). CONCLUSIONS: Elevated plasma CRP robustly associated with increased risk of atrial fibrillation; however, genetically elevated CRP levels did not. This suggests that elevated plasma CRP per se does not increase atrial fibrillation risk.
Authors:
Sarah C W Marott; Børge G Nordestgaard; Jeppe Zacho; Jens Friberg; Gorm B Jensen; Anne Tybjaerg-Hansen; Marianne Benn
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of the American College of Cardiology     Volume:  56     ISSN:  1558-3597     ISO Abbreviation:  J. Am. Coll. Cardiol.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-27     Completed Date:  2010-09-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8301365     Medline TA:  J Am Coll Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  789-95     Citation Subset:  AIM; IM    
Copyright Information:
Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Affiliation:
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Atrial Fibrillation / blood,  etiology*
C-Reactive Protein / analysis*,  genetics
Cross-Sectional Studies
Female
Genotype
Humans
Male
Mendelian Randomization Analysis*
Middle Aged
Polymorphism, Genetic
Prospective Studies
Chemical
Reg. No./Substance:
9007-41-4/C-Reactive Protein

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