Inorganic phosphate and FGF‐23 predict outcome in stable systolic heart failure

Plischke, Max; Neuhold, Stephanie; Adlbrecht, Christopher; Bielesz, Bernhard; Shayganfar, Sascha; Bieglmayer, Christian; Szekeres, Thomas; Hörl, Walter H.; Strunk, Guido; Vavken, Patrick; Pacher, Richard; Hülsmann, Martin

doi:10.1111/j.1365-2362.2011.02631.x

Cited by 69 publications

(82 citation statements)

References 42 publications

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“…This natural history introduces the possibility of a "reverse causal" process in which elevated FGF-23 could reflect an early consequence rather than an upstream cause of heart failure. 28 This scenario is also unlikely to explain our results because patients with a history of New York Heart Association class 3-4 heart failure were excluded from the CRIC study and our results were equally strong in lag analyses that exclusively considered incident heart failure events that occurred at least 1 year after FGF-23 was measured. Although our primary goal was to study novel disease mechanisms rather than to determine the predictive utility of FGF-23 as a biomarker of future heart failure risk, its independent association with congestive heart failure even after adjustment for NT-proBNP levels suggests that future studies should investigate FGF-23 in a panel of risk prediction biomarkers for congestive heart failure events.…”

Section: Discussionmentioning

confidence: 78%

Fibroblast Growth Factor-23 and Cardiovascular Events in CKD

Scialla

Xie

Rahman

et al. 2014

Journal of the American Society of Nephrology

381

263

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An elevated level of fibroblast growth factor-23 (FGF-23) is the earliest abnormality of mineral metabolism in CKD. High FGF-23 levels promote left ventricular hypertrophy but not coronary artery calcification. We used survival analysis to determine whether elevated FGF-23 is associated with greater risk of adjudicated congestive heart failure (CHF) and atherosclerotic events (myocardial infarction, stroke, and peripheral vascular disease) in a prospective cohort of 3860 participants with CKD stages 2-4 (baseline estimated GFR [eGFR], 44615 ml/min per 1.73 m 2 ). During a median follow-up of 3.7 years, 360 participants were hospitalized for CHF (27 events/1000 person-years) and 287 had an atherosclerotic event (22 events/1000 person-years). After adjustment for demographic characteristics, kidney function, traditional cardiovascular risk factors, and medications, higher FGF-23 was independently associated with graded risk of CHF (hazard ratio [HR] . Elevated FGF-23 was associated more strongly with CHF than with atherosclerotic events (P=0.02), and uniformly was associated with greater risk of CHF events across subgroups stratified by eGFR, proteinuria, prior heart disease, diabetes, BP control, anemia, sodium intake, income, fat-free mass, left ventricular mass index, and ejection fraction. Thus, higher FGF-23 is independently associated with greater risk of cardiovascular events, particularly CHF, in patients with CKD stages 2-4.

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Section: Discussionmentioning

confidence: 78%

Fibroblast Growth Factor-23 and Cardiovascular Events in CKD

Scialla

Xie

Rahman

et al. 2014

Journal of the American Society of Nephrology

381

263

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“…13,14,23,25 Faul et al 13 showed hypertrophic growth in isolated neonatal rat cardiomyocytes and activation of fetal gene programs responsible for cardiac hypertrophy after treatment with FGF-23 in vitro and in vivo. Further experimental studies are required to clarify the specific role of FGF-23 in progression of HF.…”

Section: Discussionmentioning

confidence: 99%

“…Although FGF-23 has been extensively studied in patients with chronic kidney disease and the general population, prospective data in patients with HF are rare. Only 2 studies with limited numbers of participants assessed FGF-23 in this patient group to date: Plischke et al 23 demonstrated an independent prognostic value of FGF-23 for all-cause mortality in 99 consecutive outpatients with HFrEF during a median followup of 35 months. Gruson et al 24 showed similar results in 73 HFrEF patients with a follow-up time of 6 years.…”

Section: Discussionmentioning

confidence: 99%

Fibroblast Growth Factor 23 Is an Independent and Specific Predictor of Mortality in Patients With Heart Failure and Reduced Ejection Fraction

Koller

Kleber

Brandenburg

et al. 2015

Circ: Heart Failure

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Background— Strategies to improve risk prediction are of major importance in patients with heart failure (HF). Fibroblast growth factor 23 (FGF-23) is an endocrine regulator of phosphate and vitamin D homeostasis associated with an increased cardiovascular risk. We aimed to assess the prognostic effect of FGF-23 on mortality in HF patients with a particular focus on differences between patients with HF with preserved ejection fraction and patients with HF with reduced ejection fraction (HFrEF). Methods and Results— FGF-23 levels were measured in 980 patients with HF enrolled in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study including 511 patients with HFrEF and 469 patients with HF with preserved ejection fraction and a median follow-up time of 8.6 years. FGF-23 was additionally measured in a second cohort comprising 320 patients with advanced HFrEF. FGF-23 was independently associated with mortality with an adjusted hazard ratio per 1-SD increase of 1.30 (95% confidence interval, 1.14–1.48; P <0.001) in patients with HFrEF, whereas no such association was found in patients with HF with preserved ejection fraction (for interaction, P =0.043). External validation confirmed the significant association with mortality with an adjusted hazard ratio per 1 SD of 1.23 (95% confidence interval, 1.02–1.60; P =0.027). FGF-23 demonstrated an increased discriminatory power for mortality in addition to N-terminal pro–B-type natriuretic peptide ( C -statistic: 0.59 versus 0.63) and an improvement in net reclassification index (39.6%; P <0.001). Conclusions— FGF-23 is independently associated with an increased risk of mortality in patients with HFrEF but not in those with HF with preserved ejection fraction, suggesting a different pathophysiologic role for both entities.

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“…Additionally, klotho-FGF23 is strongly involved in cardiovascular (patho-) physiology. Studies in various patient populations have consistently shown that high levels of FGF23 are associated with dismal outcome and elevated cardiovascular event rates (5)(6)(7)(8)(9)(10)(11)(12). In vivo FGF23 application directly leads to myocardial hypertrophy in murine models (13).…”

Section: Introductionmentioning

confidence: 98%