Liver stiffness not fatty liver disease is associated with atrial fibrillation: The Rotterdam study

Background & aims: Fatty liver disease has become the most prevalent chronic liver disease globally and is linked to cardiovascular disease, including arrhythmias. However, there have been inconsistent reports on the association between fatty liver disease and atrial fibrillation, while the role of liver stiffness in this association remains unclear.

Methods: Within the Rotterdam Study, a large prospective ongoing cohort, participants attending the abdominal ultrasound program between 2009-2014 were included. Exclusion criteria were no atrial fibrillation data or >20% missing data across analysis variables. Steatosis was assessed by ultrasound, liver stiffness by transient elastography and atrial fibrillation by 12-lead electrocardiograms. Incident atrial fibrillation was based on medical records and complete until 2014. Logistic and Cox-regression were used to quantify associations between fatty liver disease and atrial fibrillation.

Results: We included 5,825 participants (aged 69.5±9.1, 42.9% male), 35.7% had steatosis, liver stiffness measurement was available in 73.3%, and 7.0% had prevalent atrial fibrillation. Steatosis was not associated with prevalent atrial fibrillation in fully adjusted models (odds ratio [OR] 0.80; 95% CI 0.62-1.03), findings were consistent for non-alcoholic or metabolic dysfunction-associated fatty liver disease. Liver stiffness was significantly associated with prevalent atrial fibrillation (OR 1.09 per kPa, 95% CI 1.03-1.16); however, this was only persistent among those without steatosis (OR 1.18 per kPa, 95% CI 1.08-1.29). Lastly, no associations were found between steatosis (hazard ratio 0.88; 95% CI 0.59-1.33; follow-up 2.1 [1.1-3.2] years) and incident atrial fibrillation.

Conclusions: Fatty liver disease was not associated with prevalent or incident atrial fibrillation, while liver stiffness was significantly associated with atrial fibrillation, especially among those without steatosis. This association might be driven by venous congestion instead of fibrogenesis, but this awaits further validation. We recommend assessing cardiovascular health in participants with high liver stiffness, especially in the absence of overt liver disease.

Clinical trial number: NTR6831.

Lay summary: There have been inconsistent reports about the potential links between fatty liver disease and atrial fibrillation (an irregular and often very fast heart rhythm). Herein, we show that liver stiffness (which is a marker of liver fibrosis), but not fatty liver disease, was associated with a higher prevalence of atrial fibrillation. We hypothesis that atrial fibrillation, rather than fibrosis, may be the cause of increased liver stiffness in participants without overt liver disease.