Growth Differentiation Factor 15 and the Subsequent Risk of Atrial Fibrillation: The Atherosclerosis Risk in Communities Study

Background: Growth differentiation factor 15 (GDF-15) is a stress-responsive biomarker associated with several types of cardiovascular diseases. However, conflicting results have been reported regarding its association with incident atrial fibrillation (AF) in the general population. Methods: In 10 234 White and Black Atherosclerosis Risk in Communities (ARIC) Study participants (mean age 60 years, 20.5% Blacks) free of AF at baseline (1993 to 1995), we quantified the association of GDF-15 with incident AF using Cox regression models. GDF-15 concentration was measured by an aptamer-based proteomic method. AF was defined as AF diagnosis by electrocardiogram at subsequent ARIC visits or AF diagnosis in hospitalization records or death certificates. Harrell's c-statistic and categorical net reclassification improvement were computed for risk discrimination and reclassification. Results: There were 2217 cases of incident AF over a median follow-up of 20.6 years (incidence rate 12.3 cases/1000 person-years). After adjusting for potential confounders, GDF-15 was independently associated with incident AF, with a hazard ratio (HR) of 1.42 (95% CI, 1.24-1.62) for the top vs bottom quartile. The result remained consistent (HR 1.23 [95% CI, 1.07-1.41]) even after further adjusting for 2 cardiac biomarkers, cardiac troponin T and natriuretic peptide. The results were largely consistent across demographic subgroups. The addition of GDF-15 modestly improved the c-statistic by 0.003 (95% CI, 0.001-0.006) beyond known risk factors of AF. Conclusions: In this community-based biracial cohort, higher concentrations of GDF-15 were independently associated with incident AF, supporting its potential value as a clinical marker of AF risk.