Fibroblast growth factor 23 in acute myocardial infarction complicated by cardiogenic shock: a biomarker substudy of the Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) trial

Georg Fuernau, Janine Pöss, Daniel Denks, Steffen Desch, Gunnar H Heine, Ingo Eitel, Sarah Seiler, Suzanne de Waha, Sebastian Ewen, Andreas Link, Gerhard Schuler, Volker Adams, Michael Böhm, Holger Thiele, Georg Fuernau, Janine Pöss, Daniel Denks, Steffen Desch, Gunnar H Heine, Ingo Eitel, Sarah Seiler, Suzanne de Waha, Sebastian Ewen, Andreas Link, Gerhard Schuler, Volker Adams, Michael Böhm, Holger Thiele

Abstract

Introduction: Cardiogenic shock (CS) is the leading cause of death in patients hospitalized with acute myocardial infarction (AMI). Biomarkers might help in risk stratification and understanding of pathophysiology. Preliminary data suggests that patients with CS face a profound increase in the osteocyte-derived hormone fibroblast growth factor 23 (FGF-23), which acts as a negative regulator of serum phosphate levels. The present study aimed to assess the predictive role of FGF-23 for clinical outcome in a large cohort of CS patients with and without renal dysfunction.

Methods: In the randomized Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) trial, 600 patients with CS complicating AMI were assigned to therapy with or without IABP. Our predefined biomarker substudy included 182 patients. Blood sampling was performed in a standardized procedure at three different time points (day 1 (day of admission), day 2 and day 3). Differences in outcome of patients with FGF-23 levels<and>median were compared by log-rank testing. Stepwise logistic regression modeling was performed to identify predictors of death at 30 days and Cox regression analysis for time to death during the first year.

Results: At all three time points, nonsurvivors had significantly higher FGF-23 levels compared to survivors (P<0.001 for all). Patients with FGF-23 levels above the median (395 RU/mL [interquartile range 102;2,395]) were characterized by an increased 30-day mortality and 1-year mortality. In multivariable analysis FGF-23 levels remained independent predictors for 30-day (odds ratio per 10log 1.80, 95% confidence interval (CI) 1.11 to 2.92; P=0.02) and 1-year mortality (hazard ratio 1.50, 95% CI 1.11 to 2.04, P=0.009). After stratifying the patients according to their baseline serum creatinine levels, the negative prognostic association of increased FGF-23 was only significant in those with serum creatinine greater than median.

Conclusions: In CS, high levels of FGF-23 are independently related to a poor clinical outcome. However, this prognostic association appears only to apply in patients with impaired renal function.

Trial registration: ClinicalTrials.gov NCT00491036. Registered 22 June 2007.

Figures

Figure 1
Figure 1
Study flow. FGF-23, fibroblast growth factor 23.
Figure 2
Figure 2
Levels of FGF-23 on the different time points for 30-day survivors and nonsurvivors. FGF-23: fibroblast growth factor 23.
Figure 3
Figure 3
Kaplan-Meier curves for patients with FGF-23 levels > median (red dashed line) and < median (blue line) for the overall cohort (A) and as landmark analysis for patients surviving until day 30 (B). FGF-23: fibroblast growth factor 23; HR: hazard ratio; CI: confidence interval.
Figure 4
Figure 4
Kaplan-Meier curves for patients with FGF-23 levels > median (red dashed line) and < median (blue line) for patients with baseline serum creatinine > median (A) and < median (B). FGF-23: fibroblast growth factor 23; HR: hazard ratio; CI: confidence interval.
Figure 5
Figure 5
Forest plot for odds ratios of FGF-23 levels > median for short- and long-term survival grouped by baseline serum creatinine > median and < median. FGF-23: fibroblast growth factor 23; OR: odds ratio; CI: confidence interval.

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