YKL-40 levels and atrial fibrillation in the general population

Atrial fibrillation is associated with inflammation. In contrast to inflammatory markers like C-reactive protein (CRP) and fibrinogen produced in the liver, YKL-40 is produced at the site of inflammation including in the myocardium. We hypothesized that elevated plasma YKL-40 levels associate with increased risk of atrial fibrillation.

We measured plasma YKL-40 in 8731 participants from the prospective Copenhagen City Heart Study including 896 individuals who developed atrial fibrillation during up to 18 years of follow-up. Additionally, we measured YKL-40 in 6621 individuals from the cross-sectional Copenhagen General Population Study including 337 cases with atrial fibrillation. A YKL-40 level >95% percentile (>204 μg/L) versus <25% percentile (<36 μg/L) associated prospectively with a 2.10-fold (95%CI:1.43-3.09) increased risk of atrial fibrillation. Hazard ratios attenuated slightly after multifactorial adjustment to 2.01 (1.35-2.98), and further after additional adjustment for heart failure to 1.89 (1.27-2.80), for plasma CRP to 1.79 (1.20-2.67), and for fibrinogen levels to 1.89 (1.27-2.81). Adjusting multifactorially including both heart failure, CRP, and fibrinogen attenuated the risk of atrial fibrillation to 1.79 (1.20-2.67). These findings were supported in the cross-sectional study with an odds ratio of 2.73 (1.46-5.11) for a YKL-40 level >95% percentile versus <25% percentile, attenuating to an odds ratio of 2.13 (1.09-4.18) when adjusting multifactorially including heart failure, CRP, and fibrinogen.

Elevated plasma YKL-40 levels robustly associated with increased risk of atrial fibrillation originating from hospital admissions or visits to the emergency department, independent of heart failure, and CRP and fibrinogen levels. These findings need to be confirmed in other independent studies.