ABSTRACT
Background Previously, we identified associations of two circulating secondary bile acids (glycocholenate and glycolithocolate sulfate) with atrial fibrillation (AF) risk among African Americans. We aimed to replicate these findings in an independent sample including both whites and African Americans, and performed a new metabolomic analysis in the combined sample.
Methods We studied 3,922 participants from the ARIC cohort followed between 1987 and 2013. Of these, 1,919 had been included in the prior analysis and 2,003 were new samples. Metabolomic profiling was done in baseline serum samples using gas and liquid chromatography mass spectrometry. AF was ascertained from electrocardiograms, hospitalizations, and death certificates. We used multivariable Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (95%CI) of AF by one standard deviation difference of metabolite levels.
Results Over a mean follow-up of 20 years, 608 participants developed AF. Glycocholenate sulfate was associated with AF in the replication and combined samples (HR 1.10, 95%CI 1.00, 1.21 and HR 1.13, 95%CI 1.04, 1.22, respectively). Glycolithocolate sulfate was not related to AF risk in the replication sample (HR 1.02, 95%CI 0.92, 1.13). An analysis of 245 metabolites in the combined cohort identified three additional metabolites associated with AF after multiple-comparison correction: pseudouridine (HR 1.18, 95%CI 1.10, 1.28), uridine (HR 0.86, 95%CI 0.79, 0.93) and acisoga (HR 1.17, 95%CI 1.09, 1.26).
Conclusion We replicated a prospective association between a previously identified secondary bile acid, glycocholenate sulfate, and AF incidence, and identified new metabolites involved in nucleoside and polyamine metabolism as markers of AF risk.
Footnotes
Target journal: Journal of the American Heart Association
Disclosures: No relevant conflicts of interest