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

Abstract 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.