Growth differentiation factor-15 predicts major cardiac adverse events and all-cause mortality in patients with atrial fibrillation

Objective Growth differentiation factor-15 (GDF-15) has recently been introduced as a potential biomarker for predicting risk of cardiovascular events and mortality in patients with atrial fibrillation (AF) and is awaiting evaluation in clinical practice.

Material and Methods We prospectively included 362 patients with non-valvular AF (mean age: 71 years, 37 % female) into an all-comers cohort study. Relationship of GDF-15 with all-cause mortality, major cardiac adverse events (MACE), and bleeding events was analyzed using Cox regression. Survival analysis for all-cause death was based on the national death records. MACE and bleeding events were recorded at personal follow-up at a 6 to 12-month interval. Further, we evaluated the ABC-death risk score, a recently developed GDF-15-based prognostic score, regarding its predictive ability for all-cause mortality.

Results Over a median observation period of 4.3 years, we recorded 81 (23.3 %) deaths. Furthermore, we observed 45 MACE and 34 clinically relevant bleeding events during a median follow-up of 316 days. GDF-15 was independently associated with all-cause mortality (adjusted hazard ratio [HR] per double increase 2.33, 95 % confidence interval [CI] 1.74-3.13) and MACE (adjusted HR per double increase 2.33, 95%CI 1.60-3.39) but showed no association with bleeding events. Six-year survival probability of patients above and below the median GDF-15 serum level (1428.5 ng/L) was 44 % (95%CI 34-57) and 84 % (95%CI 76-93), respectively. The ABC-death risk score, which includes GDF-15, demonstrated good predictive ability for death in our cohort (c-statistic 0.80).

Conclusion GDF-15 predicts risk of all-cause mortality and MACE in patients with non-valvular AF. Further, we externally validated the ABC-death risk score in a “real-world” cohort. Our data suggests that introduction of GDF-15 in clinical practice could enhance risk prediction of morbidity and mortality in AF patients.

Fig. 1 Patients were stratified into low and high serum level groups according to levels below or above the median growth differentiation factor-15 (GDF-15) level (median 1428.5, range 343-43218 ng/L). After 1, 3 and 6 years, survival probability for patients with low GDF-15 levels was 99% (95%CI 97-100), 93% (95%CI 90-98), 84% (95%CI 76-93), and 88% (95%CI 84-93), 72% (95%CI 65-80), 44% (95%CI 34-57) for patients in the high level group.

Publication History

Article published online:
18 June 2021