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

Eur J Intern Med. 2021 Jun:88:35-42. doi: 10.1016/j.ejim.2021.02.011. Epub 2021 Mar 9.


Background: Growth-differentiation factor-15 (GDF-15) has recently been described as a potential biomarker for predicting risk of mortality and cardiovascular events in patients with atrial fibrillation (AF) but requires validation in clinical practice.

Methods: The study population consisted of 362 patients (mean age: 71 years, 37% women) with non-valvular AF included in a prospective cohort study. Relationship of GDF-15 with all-cause mortality and major adverse cardiac events (MACE) was analyzed using Cox regression. Survival analysis stratified by GDF-15 was based on national death records, while MACE was recorded at personal follow-up. Further, we evaluated the recently developed GDF-15 based prognostic score towards prediction of all-cause mortality (ABC-death score).

Results: Over a median observation period of 4.3 years, 81 (23.3%) patients died, and over a median personal follow-up of 316 days 47 MACE occurred. GDF-15 was independently associated with all-cause mortality (adjusted HR per double increase 2.33, 95%CI 1.74-3.13) and MACE (adjusted HR per double increase 2.33, 95%CI 1.60-3.39). GDF-15 levels, measured at follow-up, were similarly associated with mortality, and longitudinal measurements of GDF-15 did not significantly differ. Six-year survival probability of patients above vs. below the median GDF-15 level was 44% (95%CI 34-57) and 84% (95%CI 76-93), respectively. The ABC-death score revealed a C-statistic of 0.80.

Conclusion: GDF-15 predicts risk of all-cause mortality and MACE in patients with non-valvular AF. Further, the ABC-death score showed good predictive accuracy in a "real-world" cohort. Therefore, introduction of GDF-15 into clinical practice would enhance risk prediction of morbidity and mortality in AF patients.

Keywords: Atrial fibrillation; Biomarkers; Growth Differentiation Factor 15; Mortality; Prognosis.

MeSH terms

  • Aged
  • Atrial Fibrillation*
  • Biomarkers
  • Female
  • Follow-Up Studies
  • Growth Differentiation Factor 15*
  • Humans
  • Male
  • Mortality*
  • Prospective Studies
  • Risk Factors


  • Biomarkers
  • Growth Differentiation Factor 15