Abstract 2688: Genetically Elevated C-reactive Protein and Atrial Fibrillation
Background Elevated levels of C-reactive protein (CRP) associate with increased risk of atrial fibrillation. We tested whether this is a causal relationship using a Mendelian randomization design.
Method We studied 10,276 individuals from the prospective Copenhagen City Heart Study, including 771 individuals who developed atrial fibrillation during a median of 14 years follow-up. We re-tested the hypothesis in another 36,600 persons from the cross-sectional Copenhagen General Population Study, including 1,340 cases with atrial fibrillation. Individuals were genotyped for four CRP gene polymorphisms and had high-sensitivity CRP levels measured.
Results A CRP level in the upper fifth quintile associated with a 2.19 fold (95% CI: 1.54 –3.10) increased risk of atrial fibrillation, corresponding to a 1.11 fold increase (1.01–1.22) in risk for a doubling of plasma CRP levels. Genotype combinations of four CRP polymorphisms associated with up to a 64% increase in plasma CRP levels (p<0.001). Assuming causality between CRP levels and atrial fibrillation, genetically elevated plasma CRP levels should confer the same increase in disease risk as that observed for elevated plasma CRP levels encountered in the two general population studies. However, a doubling of plasma CRP levels due to CRP genotype combinations was only associated with a causal hazard ratio for atrial fibrillation of 0.89 (0.52–1.53), contradicting a causal relationship.
Conclusion Elevated plasma CRP associated with increased risk of atrial fibrillation, CRP genotype associated with elevated levels of plasma CRP, but genetically elevated levels of CRP were not associated with increased risk of atrial fibrillation. This suggests that elevated plasma CRP levels per se do not cause atrial fibrillation.