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

Reindl, Martin; Reinstadler, Sebastian Johannes; Feistritzer, Hans‐Josef; Mueller, Lukas A.; Koch, Constantin; Mayr, Agnes; Theurl, Markus; Kirchmair, Rudolf; Klug, Gert; Metzler, Bernhard

doi:10.1136/heartjnl-2016-310520

Cited by 45 publications

(39 citation statements)

References 32 publications

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“…Additionally, FGF‐23 may downregulate soluble α‐klotho,34 an enzyme with anti‐aging effects that was shown to protect the heart against cardiac hypertrophy and cardiac remodeling 35, 36. In a study by Reindl et al, FGF‐23 was significantly higher in patients who developed LV remodeling post ST‐segment–elevation myocardial infarction even after adjustment for biomarkers of myocardial necrosis, myocardial stress, and inflammation 37. Finally, FGF‐23 may promote myocardial fibrosis through upregulation of β‐catenin, transforming growth factor‐β, procollagen I, and procollagen III, which may exacerbate diastolic dysfunction 38…”

Section: Discussionmentioning

confidence: 99%

Fibroblast Growth Factor‐23 and Heart Failure With Reduced Versus Preserved Ejection Fraction: MESA

Almahmoud

Soliman

Bertoni

et al. 2018

JAHA

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BackgroundHigher fibroblast growth factor‐23 (FGF‐23) levels are associated with incident heart failure (HF) in MESA (the Multiethnic Study of Atherosclerosis). FGF‐23 is also associated with left ventricular hypertrophy. Whether the FGF‐23 association with HF is similar for heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) is not well established.Methods and ResultsWe studied 6542 participants (mean age 62±10 years, 53% women, mean estimated glomerular filtration rate of 81±18 mL/min per 73 m2) from MESA who were free of cardiovascular disease at baseline (2000–2002). HF events were ascertained by an adjudication committee for a median follow‐up of 12.1 years. We classified HF events as HFrEF (ejection fraction [EF] <50%) or HFpEF [EF] ≥50%) at the time of diagnosis. Cox proportional hazard regression was used to compute hazard ratios and 95% confidence intervals for the association between baseline serum FGF‐23 and incident HFrEF and HFpEF. A total of 134 events were classified as HFpEF, 151 HFrEF, and 49 unknown EF. Following imputation, 149 were classified as HFpEF, 176 HFrEF, and 291 participants had HF (34 participants had HFpEF then HFrEF). In the fully adjusted model, higher FGF‐23 levels were associated with incident HFpEF but not with HFrEF (hazard ratio 1.29, 95% confidence interval, 1.08–1.54) versus (hazard ratio 1.04, 95% confidence interval, 0.84–1.29) for each 20 pg/mL higher serum FGF‐23 concentration.Conclusions FGF‐23 association with HF is driven by the association with HFpEF but not with HFrEF in a population‐based cohort. Further studies are needed to determine the pathological mechanisms mediating this association.

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Section: Discussionmentioning

confidence: 99%

Fibroblast Growth Factor‐23 and Heart Failure With Reduced Versus Preserved Ejection Fraction: MESA

Almahmoud

Soliman

Bertoni

et al. 2018

JAHA

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“…Furthermore, a risk score adding PWV to major clinical prognostic determinants of MACCE (age, NT‐proBNP, multivessel disease) was developed. As described in a previous study, 1 point was given for each of these parameters when they were above the optimal cutoff value derived from receiver operating characteristic analysis 18. This resulted in a score ranging from 0 to 4 points.…”

Section: Methodsmentioning

confidence: 99%

Prognostic Value of Aortic Stiffness in Patients After ST‐Elevation Myocardial Infarction

Feistritzer

Klug

Reinstadler

et al. 2017

JAHA

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BackgroundHigh aortic stiffness has been shown to be a strong predictor of morbidity and mortality in the general population and several patient cohorts. However, in patients after ST‐elevation myocardial infarction, the prognostic value of high aortic stiffness is unknown so far.Methods and ResultsThis prospective observational study included 160 consecutive patients with first acute ST‐elevation myocardial infarction. Aortic pulse wave velocity (PWV) was measured 2 (interquartile range 2‐4 days) days after infarction using cardiac magnetic resonance imaging. The primary end point was defined as a composite end point of major adverse cardiac and cerebrovascular events (MACCE) comprising death, nonfatal myocardial reinfarction, new congestive heart failure, and stroke. During a median follow‐up of 1.2 years (interquartile range 1.0‐3.1 years), 19 (12%) MACCE events occurred. Kaplan‐Meier analysis showed a significantly lower MACCE‐free survival in patients with high PWV (PWV >7.3 m/s, log‐rank P=0.003). Multivariable Cox regression analysis revealed PWV >7.3 m/s to be an independent predictor of MACCE after adjustment for age, sex, mean blood pressure, N‐terminal pro–brain natriuretic peptide levels, presence of multivessel disease, and left ventricular stroke volume (hazard ratios ≥3.5; 95% confidence interval 1.4‐13.3; all P≤0.018). In reclassification analysis the addition of PWV to a risk model comprising major clinical prognostic parameters led to a net reclassification improvement of 0.11 (95% confidence interval 0.06‐0.17; P<0.001).ConclusionsIncreased aortic stiffness is an independent predictor of MACCE after acute ST‐elevation myocardial infarction. Moreover, the assessment of aortic stiffness in addition to classical risk factors significantly improved early risk stratification.

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“…24, 25 Reindl et al showed in a recent study that the serum FGF23 level, measured 2 days after AMI onset, was associated with aggravated long-term LV remodeling, as assessed by cardiac magnetic resonance imaging and defined as at least a 20% increase in LV end-diastolic volume between the baseline scan and follow-up scan at 4 months. 12 As in the current study, they did not assess whether an elevated level of FGF23 predicted LV remodeling independent of other cardiac biomarkers or calcium/phosphate-related parameters, presumably because of the small sample size. Pöss et al showed that circulating FGF23 levels were higher among patients with cardiogenic shock than among those with uncomplicated AMI, which suggests that the serum FGF23 level may change according to the patient's physi-FGF23 in AMI log(relative FGF237d) significantly and negatively correlated with the change in LVEF between admission and 6 months afterward.…”

Section: Discussionmentioning

confidence: 99%

“…11, 12 Recent studies have shown that FGF23 is expressed and regulated in the heart and vessels. 13, 14 Notably, cardiac FGF23 expression and serum FGF23 levels were found to be increased in a rodent model of myocardial infarction (MI).…”

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confidence: 99%

“…13, 14 Notably, cardiac FGF23 expression and serum FGF23 levels were found to be increased in a rodent model of myocardial infarction (MI). 15 Considering that higher levels of circulating FGF23 predict aggravated left ventricular (LV) remodeling after reperfusion of acute MI (AMI) in humans, 12 how the serum FGF23 concentration, as well as cardiac FGF23 expression, is regulated in patients with AMI may provide important clinical information. To this end, we investigated whether serum FGF23 levels are altered in patients diagnosed with AMI and, if so, what factors are related to the changes in serum FGF23 in these patients.…”

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confidence: 99%

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Changes in Serum Fibroblast Growth Factor 23 in Patients With Acute Myocardial Infarction

Takahashi

Ozeki

Fujisaka

et al. 2018

Circ J

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outcome or aggravated cardiac remodeling among patients. 11,12 Recent studies have shown that FGF23 is expressed and regulated in the heart and vessels. 13, 14 Notably, cardiac FGF23 expression and serum FGF23 levels were found to be increased in a rodent model of myocardial infarction (MI). 15 Considering that higher levels of circulating FGF23 predict aggravated left ventricular (LV) remodeling after reperfusion of acute MI (AMI) in humans, 12 how the serum FGF23 concentration, as well as cardiac FGF23 expression, is regulated in patients with AMI may provide important clinical information. To this end, we investigated whether serum FGF23 levels are altered in patients diagnosed with AMI and, if so, what factors are related to the changes in serum FGF23 in these patients. Methods Ethics StatementThe current retrospective study was approved by the Ethics Committee of the Osaka Medical College and conducted B y suppressing the renal reabsorption of phosphate, fibroblast growth factor 23 (FGF23) plays a critical role in maintaining phosphate homeostasis together with α-Klotho. 1,2 FGF23 is primarily derived from bone, 3 and exerts its phosphaturic effect via FGF receptor (FGFR) 1c expressed on proximal renal tubules. Serum FGF23 levels are elevated in individuals with renal failure, presumably to counter-regulate the decrease in urinary inorganic phosphate (iP). Several epidemiological studies have shown that individuals with increased serum FGF23 levels may have poor clinical outcomes, 4 incident kidney disease, and cardiac hypertrophy, 5-7 suggesting that FGF23 may be a factor that mediates the increase in cardiovascular disorders observed among patients with renal dysfunction. Differing from its phosphaturic effect, FGF23 may promote cardiac hypertrophy via the activation of FGFR4 expressed on cardiomyocytes without requiring the coexistence of α-Klotho. 8,9 It has also been found that the association between serum FGF23 and cardiac hypertrophy is not limited to those with impaired renal function. 10 Raised FGF23 levels increase the risk of worse cardiac Background: Fibroblast growth factor 23 (FGF23) induces cardiac remodeling. We investigated the changes in serum FGF23 levels in patients diagnosed with acute myocardial infarction (AMI).

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

Abstract: Circulating FGF-23 is independently associated with LV remodelling after reperfused STEMI. A comprehensive multimarker strategy that includes FGF-23 provides incremental prognostic value for prediction of LV remodelling.

Cited by 45 publications

References 32 publications

Fibroblast Growth Factor‐23 and Heart Failure With Reduced Versus Preserved Ejection Fraction: MESA

Fibroblast Growth Factor‐23 and Heart Failure With Reduced Versus Preserved Ejection Fraction: MESA

Prognostic Value of Aortic Stiffness in Patients After ST‐Elevation Myocardial Infarction

Changes in Serum Fibroblast Growth Factor 23 in Patients With Acute Myocardial Infarction

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