Relation of circulating liver transaminase concentrations to risk of new-onset atrial fibrillation

Abstract

Heart failure, a strong risk factor for atrial fibrillation (AF), is often accompanied by elevated liver transaminases. The aim of this study was to test the hypothesis that elevated transaminases are associated with the risk for incident AF in the community. A total of 3,744 participants (mean age 65 ± 10 years, 56.8% women) from the Framingham Heart Study Original and Offspring cohorts, free of clinical heart failure, were studied. Cox proportional-hazards models adjusted for standard AF risk factors (age, gender, body mass index, systolic blood pressure, electrocardiographic PR interval, antihypertensive treatment, smoking, diabetes, valvular heart disease, and alcohol consumption) were examined to investigate associations between baseline serum transaminase levels (alanine transaminase and aspartate transaminase) and the incidence of AF over up to 10 years (29,099 person-years) of follow-up. During follow-up, 383 subjects developed AF. The 2 transaminases were significantly associated with greater risk for incident AF (hazard ratio expressed per SD of natural logarithmically transformed biomarker: alanine transaminase hazard ratio 1.19, 95% confidence interval 1.07 to 1.32, p = 0.002; aspartate transaminase hazard ratio 1.12, 95% confidence interval 1.01 to 1.24, p = 0.03). The associations between transaminases and AF remained consistent after the exclusion of participants with moderate to severe alcohol consumption. However, when added to known risk factors for AF, alanine transaminase and aspartate transaminase only subtly improved the prediction of AF. In conclusion, elevated transaminase concentrations are associated with increased AF incidence. The mechanisms by which higher mean transaminase concentrations are associated with incident AF remain to be determined.

Figure 1

Cumulative hazard curves for the incidence of atrial fibrillation (AF) are depicted by transaminase values ≤40 U/l vs. >40 U/l; p-values are derived from log-rank tests. Left Panel: ALT – alanine aminotransferase; Right Panel: AST – aspartate aminotransferase.