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

Abstract

IntroductionCardiogenic 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.MethodsIn 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.ResultsAt 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.ConclusionsIn 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 registrationClinicalTrials.gov NCT00491036. Registered 22 June 2007.

Fibroblast growth factor 23 as novel biomarker for early risk stratification after ST-elevation myocardial infarction

“…Our results could confirm this previous observation by showing a relative low FGF-23 concentration in haemodynamically stable patients with STEMI, especially as compared with the previously published FGF-23 values in CS 6 22. It was hypothesised that this tremendous increase of FGF-23 in CS is mainly caused by the neuroendocrinological and haemodynamic alterations, not by the myocardial ischaemia per se 22. Indeed, we could not find any significant correlation between CMR-determined myocardial or microvascular damage and FGF-23 concentrations.…”

“…In the study by Pöss et al ,6 uncomplicated patients with AMI did not show significantly higher FGF-23 levels than patients with stable CAD, however hampered by the very small number of patients with AMI (n=18). Our results could confirm this previous observation by showing a relative low FGF-23 concentration in haemodynamically stable patients with STEMI, especially as compared with the previously published FGF-23 values in CS 6 22. It was hypothesised that this tremendous increase of FGF-23 in CS is mainly caused by the neuroendocrinological and haemodynamic alterations, not by the myocardial ischaemia per se 22.…”

“…Pöss et al 6 studied 51 patients with CS and revealed a tremendous increase of FGF-23 levels in CS, which was associated with worse outcome. More recently, the larger study by Fuernau et al 22 including 182 patients with CS approved the association between FGF-23 and poor outcome. However, the prognostic significance of FGF-23 in haemodynamically stable patients, representing the vast majority of patients with AMI, has never been investigated so far.…”

“…Only patients with AMI complicated by cardiogenic shock (CS) were investigated in previous studies 6 22. Pöss et al 6 studied 51 patients with CS and revealed a tremendous increase of FGF-23 levels in CS, which was associated with worse outcome.…”

Strength of Fibroblast Growth Factor 23 as a Cardiovascular Risk Predictor in Chronic Kidney Disease Weaken by ProBNP Adjustment

“…FGF23 may reflect prevalent cardiovascular disease [2]. This concern has been founded upon the observation that hypertrophic and failing [20,23,28] hearts may directly produce FGF23, that particularly high FGF23 levels are found in patients with severe acute heart disease [38,39], and that patients chronically exposed to high FGF23 -such as patients with hypophosphatemic rickets/osteomalacia -do not regularly develop heart disease [40]. Experimentally, a direct role of FGF23 in the development of vascular calcification has largely been ruled out [41], and data on its contribution to left ventricular hypertrophy remains uncertain: even though several reports have suggested FGF23 to activate cardiomyocytes and induce their proliferation [8,9], later studies have questioned these findings [15][16][17][18][19][20].…”