Abstract
BACKGROUND: Peripheral blood metabolite profiles have yielded mechanistic insights into various cardiovascular disease states. We hypothesized that peripheral blood metabolite profiles would be associated with new onset atrial fibrillation (AF). METHODS AND RESULTS: The study population comprised 1892 patients without AF at baseline, who, as part the MURDOCK Cardiovascular Disease Study molecular profiling cohort (n = 2023), had previously had determination of levels of 69 metabolites from frozen, fasting plasma specimens obtained during coronary angiography. We used Cox proportional hazards models to examine the association of 13 uncorrelated metabolite factors created from these data using principal components analysis (PCA) with new occurrences of AF during a median follow up of 2.8 (0.1-4.9) years. A total of 233 patients developed new AF (12.3%) during follow up. Patients with new onset AF were older (median 67 vs. 60 years); more often white (82 vs. 71%) and male (68 vs. 60%), and had more comorbidities than those who did not develop AF. After adjustment, PCA factor 1 (medium chain acylcarnitines; hazard ratio [HR]: 1.11 [1.01-1.22]), factor 2 (short chain dicarboxylacylcarnitines; HR: 1.21 [1.09-1.34]) and factor 5 (long chain acylcarnitines; HR: 1.19 [1.06-1.34]) were associated with new onset AF. CONCLUSION: Metabolite profiles were associated with new onset AF among patients referred for coronary angiography. Validation of these observations in broader patient populations may provide better mechanistic insight into the development of AF, and may provide new opportunities for prevention and treatment.