Fibroblast growth factor-23 and the risk of cardiovascular diseases and mortality in the general population: A systematic review and dose-response meta-analysis

Liu, Menglu; Xia, Panpan; Tan, Ziqi; Song, Tiangang; Mei, Kaibo; Wang, Jingfeng; Ma, Jianyong; Jiang, Yuan; Zhang, Jing; Zhao, Yujie; Yu, Peng; Liu, Xiao

doi:10.3389/fcvm.2022.989574

Cited by 10 publications

(6 citation statements)

References 68 publications

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“…A meta‐analysis including more than 135 000 participants from the general population showed that FGF23 is an independent predictor of the development of HF, stroke, and acute myocardial infarction. 26 In the community‐based PREVEND (Prevention of Renal and Vascular End‐Stage Disease) study, a higher FGF23 level was associated with the development of HF with reduced ejection fraction but not with the appearance of HF with preserved ejection fraction during follow‐up. 27 Finally, in a secondary analysis from the Stabilization of Plaques Using Darapladib‐Thrombolysis in Myocardial Infarction 52 (SOLID‐TIMI 52) trial including 4947 patients with ACS, FGF23 was found to be an independent predictor of cardiovascular death or hospitalization by HF.…”

Section: Discussionmentioning

confidence: 99%

“…FGF23 was among those biomarkers predicting the outcome of total death, recurrent acute myocardial infarction, or HF hospitalization, although the number of clinical variables employed for adjustment was lower than in our study. A meta‐analysis including more than 135 000 participants from the general population showed that FGF23 is an independent predictor of the development of HF, stroke, and acute myocardial infarction 26 . In the community‐based PREVEND (Prevention of Renal and Vascular End‐Stage Disease) study, a higher FGF23 level was associated with the development of HF with reduced ejection fraction but not with the appearance of HF with preserved ejection fraction during follow‐up 27 .…”

Section: Discussionmentioning

confidence: 99%

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Fibroblast growth factor 23 independently predicts adverse outcomes after an acute coronary syndrome

Kallmeyer,

Pello,

Cánovas

et al. 2023

ESC Heart Failure

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AimsAbnormalities of mineral metabolism (MM) have been related to cardiovascular disorders. There are no reports on the prognostic role of MM after an acute coronary syndrome (ACS). We aim to assess the prognostic role of MM after an ACS.Methods and resultsPlasma levels of components of MM [fibroblast growth factor 23 (FGF23), calcidiol, parathormone, klotho, and phosphate], high‐sensitivity C‐reactive protein, and N‐terminal‐pro‐brain natriuretic peptide were measured in 1190 patients at discharge from an ACS. The primary outcome was a combination of acute ischaemic events, heart failure (HF) and death. Secondary outcomes were the separate components of the primary outcome. Age was 61.7 ± 12.2 years, and 77.1% were men. Median follow‐up was 5.44 (3.03–7.46) years. Two hundred and ninety‐four patients developed the primary outcome. At multivariable analysis FGF23 (hazard ratio, HR 1.18 [1.08–1.29], P < 0.001), calcidiol (HR 0.86 [0.74–1.00], P = 0.046), previous coronary or cerebrovascular disease, and hypertension were independent predictors of the primary outcome. The predictive power of FGF23 was homogeneous across different subgroups of population. FGF23 (HR 1.45 [1.28–1.65], P < 0.001) and parathormone (HR 1.06 1.01–1.12]; P = 0.032) resulted as independent predictors of HF. FGF23 (HR 1.21 [1.07–1.37], P = 0.002) and calcidiol (HR 0.72 [0.54–0.97), P = 0.028) were independent predictors of death. No biomarker predicted acute ischaemic events. FGF23 predicted independently the primary outcome in patients with estimated glomerular filtration rate > 60 mL/min/1.73 m2.ConclusionsFGF23 and other components of MM are independent predictors of HF and death after an ACS. This effect is homogeneous across different subgroups of population, and it is not limited to patients with chronic kidney disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Fibroblast growth factor 23 independently predicts adverse outcomes after an acute coronary syndrome

Kallmeyer,

Pello,

Cánovas

et al. 2023

ESC Heart Failure

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“…These findings are consistent with other published data [ 42 ]. The association of higher FGF-23 levels with the development of heart failure has also been described in patients with acute heart failure and even in the general population [ 43 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

Cardiac Rehabilitation Increases Plasma Klotho Levels

Pello Lázaro,

Villelabeitia Jaureguizar,

Franco Peláez

et al. 2024

JCM

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Background: Mineral metabolism (MM), mainly fibroblast growth factor-23 (FGF-23) and klotho, has been linked to cardiovascular (CV) diseases. Cardiac rehabilitation (CR) has been demonstrated to reduce CV events, although its potential relationship with changes in MM is unknown. Methods: We performed a prospective, observational, case-control study, with acute coronary syndrome (ACS) patients who underwent CR and control patients (matched by age, gender, left ventricular ejection fraction, diabetes, and coronary artery bypass grafting), who did not. The inclusion dates were from August 2013 to November 2017 in CR group and from July 2006 to June 2014 in control group. Clinical, biochemical, and MM biomarkers were collected at discharge and six months later. Our objective was to evaluate differences in the modification pattern of MM in both groups. Results: We included 58 CR patients and 116 controls. The control group showed a higher prevalence of hypertension (50.9% vs. 34.5%), ST-elevated myocardial infarction (59.5% vs. 29.3%), and treatment with angiotensin-converting enzyme inhibitors (100% vs. 69%). P2Y12 inhibitors and beta-blockers were more frequently prescribed in the CR group (83.6% vs. 96.6% and 82.8% vs. 94.8%, respectively). After six months, klotho levels increased in CR patients whereas they were reduced in controls (+63 vs. −49 pg/mL; p < 0.001). FGF-23 was unchanged in the CR group and reduced in controls (+0.2 vs. −17.3 RU/dL; p < 0.003). After multivariate analysis, only the change in klotho levels was significantly different between groups (+124 pg/mL favoring CR group; IC 95% [+44 to +205]; p = 0.003). Conclusions: In our study, CR after ACS increases plasma klotho levels without significant changes in other components of MM. Further studies are needed to clarify whether this effect has a causal role in the clinical benefit of CR.

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“…Burosumab could potentially yield further positive effects, given that persistently elevated FGF23 levels have the potential to negatively affect the cardiovascular system. A linear relationship had been described between FGF23 and cardiovascular mortality, independent of the chronic kidney disease status in a general adult population ( 33 ). This relationship was discovered to be age-dependent, thus underscoring the significance of klotho decline with aging in the damage caused by FGF23 ( 34 ).…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular health in pediatric patients with X-linked hypophosphatemia under two years of burosumab therapy

Brener,

Cleper,

Baruch

et al. 2024

Front. Endocrinol.

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IntroductionX-linked hypophosphatemia (XLH) is caused by an inactivating mutation in the phosphate-regulating endopeptidase X-linked (PHEX) gene whose defective product fails to control phosphatonin fibroblast growth factor 23 (FGF23) serum levels. Although elevated FGF23 levels have been linked with detrimental cardiac effects, the cardiologic outcomes in XLH patients have been subject to debate. Our study aimed to evaluate the prevalence and severity of cardiovascular morbidity in pediatric XLH patients before, during, and after a 2-year treatment period with burosumab, a recombinant anti-FGF23 antibodyMethodsThis prospective observational study was conducted in a tertiary medical center, and included 13 individuals with XLH (age range 0.6–16.2 years) who received burosumab every 2 weeks. Clinical assessment at treatment initiation and after .5, 1, and 2 years of uninterrupted treatment included anthropometric measurements and cardiologic evaluations (blood pressure [BP], electrocardiogram, conventional echocardiography, and myocardial strain imaging).ResultsThe linear growth of all patients improved significantly (mean height z-score: from -1.70 ± 0.80 to -0.96 ± 1.08, P=0.03). Other favorable effects were decline in overweight/obesity rates (from 46.2% to 23.1%) and decreased rates of elevated BP (systolic BP from 38.5% to 15.4%; diastolic BP from 38.5% to 23.1%). Electrocardiograms revealed no significant abnormality throughout the study period. Cardiac dimensions and myocardial strain parameters were within the normative range for age at baseline and remained unchanged during the study period.ConclusionCardiologic evaluations provided reassurance that 2 years of burosumab therapy did not cause cardiac morbidity. The beneficial effect of this treatment was a reduction in cardiovascular risk factors, as evidenced by the lower prevalence of both overweight/obesity and elevated BP.

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Fibroblast growth factor-23 and the risk of cardiovascular diseases and mortality in the general population: A systematic review and dose-response meta-analysis

Cited by 10 publications

References 68 publications

Fibroblast growth factor 23 independently predicts adverse outcomes after an acute coronary syndrome

Fibroblast growth factor 23 independently predicts adverse outcomes after an acute coronary syndrome

Cardiac Rehabilitation Increases Plasma Klotho Levels

Cardiovascular health in pediatric patients with X-linked hypophosphatemia under two years of burosumab therapy

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